CURRICULUM VITAE ALBERTO MUÑOZ TEROL

Lugar y fecha de nacimiento: Murcia, 05.01.1958 D.N.I.: 51.334.407-V

Domicilio particular: Santa Virgilia 14, dcha. 6ºA, 28033 Madrid E-mail:

amunoz@iib.uam.es

Inst. Investigaciones Biomédicas, Arturo Duperier 4, 28029 Madrid. Tel: 915854451 Fax:

915854401

FORMACIÓN ACADÉMICA

Licenciado (1980) y Doctor (1983) en Ciencias (Biología) por la Universidad Autónoma de

Madrid.

PREMIOS Y BECAS

- Premio Extraordinario de Licenciatura (1980); Premio Extraordinario de Doctorado

(1983).

- Premio de Caja Madrid de Tesis Doctorales en el campo de las Ciencias Biomédicas

(1983).

- Beca (1980) y Premio (1983) de la Fundación Científica de la Asociación Española contra

el Cáncer.

- Beca del Fondo de Investigaciones Sanitarias de la Seguridad Social (FIS) (1981).

- Beca Short-Term (1982) y Long-Term (1987) de la European Molecular Biology

Organization.

- Beca de la Fundación Juan March, (1986). Beca Convenio Cooperación Científ. Hispano-

Sueco (1989).

- Premio Rey Jaime I a la Investigación, Tema: "Cáncer" (1993).

- Premio Harington-De Visscher, de la European Thyroid Association (1996).

- Premio de Investigación de la Sociedad Española de Endocrinología (1997).

- Premio Max-Pierre König-Nourypharma, European Thyroid Association (1999).

- Premio de Investigación Biomédica de la Fundación Francisco Cobos (2000).

- Premio de la Fundación Jacinto Vilardell de Gastroenterología (2006).

ACTIVIDAD CIENTÍFICA

1978 - 1983 Tesina y Tesis Doctoral, Centro de Biología Molecular, CSIC-UAM, Madrid.

1984 - 1986 Técnico del Departamento Investigación, Antibióticos S.A., Madrid.

1986 - 1988 Visiting Scientist, EMBL, European Molecular Biology Laboratory, Heidelberg.

1988 - 1990 Colaborador Científico, CSIC, Instituto de Investigaciones Biomédicas (IIB),

Madrid.

1990 - 1991 Visiting Scientist, Institut für Molekulare Pathologie (Genentech-Boehringer

Ingelheim), Viena.

1991 - 1993 Investigador Científico, Instituto de Investigaciones Biomédicas, Madrid.

1999 - Profesor de Investigación del CSIC.

PUBLICACIONES

Más de 130 publicaciones en revistas internacionales, incluyendo Nature (2), Nature

Medicine (2), Cell, Journal of Clinical Investigation (2), Genes & Development, Journal

of Cell Biology (4), Human Molecular Genetics (3), EMBO Journal (3) y Cancer Research.

Otras 15 en revistas nacionales. Un libro (“Cáncer. Genes y nuevas terapias”, Madrid,

1997) y capítulos en otros 15. CONGRESOS

Un centenar de comunicaciones en C. Internacionales y más de 40 en C. Nacionales,

numerosas conferencias invitadas en Congresos internacionales, Co-chairman de Simp. en el

V Intern. Congress on Cell Biology (1992), Organizador del International Symposium on

Thyroid Hormone, Madrid (1995), Chairman Simposio en el V European Congress on

Endocrinology, Sevilla (1998), Coordinador de I Reunión Temática Nacional sobre "Control

de la Proliferación y Diferenciación celular" (1998) y del Simposio “Vitamin D and

Cancer: Promise or Reality” (2011) en la Fund. Ramón Areces y Chairman de Simposios de

Cáncer en Congresos de Soc Españolas de Biología Celular (2007, 2009, 2011),

Investigación del Cáncer (2011) y Bioquímica y Biología Molecular (2007, 2011).

DOCENCIA

Director de 16 Tesis Doctorales. Cursos y Masters sobre Cáncer: Univ. Intern. Menéndez-

Pelayo, Santander (1990, 2000, 01, 02, 11), Autónoma de Madrid (1993-2009), Complutense

de Madrid (1993, 1995-2006), León (1993, 1995, 2009), Oviedo (1994), Univ.

Hispanoamericana de La Rábida, Huelva (1994), Las Palmas (1997), Acad. Ciencias Médicas

Cataluña y Baleares, Barcelona (1996, 97), Univ. Alcalá de Henares (1995, 97, 2007-09),

Castilla-La Mancha (1998), Cantabria (1999, 01, 05), San Pablo-CEU Madrid (1999), Granada

(2000), Extremadura (Cáceres/Badajoz) (2000, 02, 05), Barcelona (2001, 02), Málaga

(2001), SEK Segovia (2001). Salamanca (2006), Sevilla (2006), Internacional de Andalucía

(2008), Córdoba (2011), Prof. Honorario Depto de Bioquímica y Director Curso Doctorado

“Cáncer. Genes, procesos y mecanismos”, Fac. Medicina, Univ. Autónoma de Madrid (1996-

2007); Co-Director Master en Oncología Molecular, Univ. Francisco de Vitoria, Madrid

(2001-02) y Co-Director del Master en Oncología Molecular, Centro Nacional de

Investigaciones Oncológicas (8 ediciones, 2003-05 a 2012-14).

ESTANCIAS EN CENTROS EXTRANJEROS

National Institute for Medical Research, Biochemistry Division, Londres, Inglaterra,

1982, 5 semanas.

European Molecular Biology Laboratory (EMBL), Heidelberg, Alemania, 1986-88, 2 años.

Karolinska Institutet, Department of Molecular Biology, Estocolmo, Suecia, 1989, 5

semanas.

Institut für Molekulare Pathologie (Genentech-Boehringer Ingelheim), Viena, Austria,

1990-91, 1 año.

LÍNEAS DE INVESTIGACIÓN

1978-1986 Mecanismo de acción del interferón humano.

1986-2000 Biología de los genes erbA y hormona tiroidea en cáncer y sistema nervioso

central.

Antagonismo entre glucocorticoides y otras hormonas con receptores nucleares

y el factor AP-1.

2000-2011 Acción de la vitamina D en cáncer de colon y de mama. Antagonismo de la

vía Wnt/-catenina. Mecanismo de acción de nuevos agentes

antitumorales de origen marino.

Coordinador del Área de Biología Molecular y Celular, Agencia Nacional de

Evaluación y Prospectiva (ANEP), Ministerio de Educación y Cultura, marzo

1997-2000.

Miembro de la Ponencia de Bioquímica, Biología Molecular y Celular, Programa

de Promoción General del Conocimiento, Ministerio de Educación y Cultura,

1996 y 1997.

Miembro de la Comisión del Area de Biología y Biomedicina, Consejo Superior

de Investigaciones Científicas, 1996-2001.

Profesor Honorario del Departamento de Bioquímica, Facultad de Medicina de la

Universidad Autónoma de Madrid, 1995-2008.

Presidente de Tribunal de Oposiciones (Biomedicina) del Consejo Superior de

Investigaciones Científicas, 1993, 2001, 2002.

Miembro del Tribunal de plazas Investigador, Instituto Municipal de

Investigación Médica, Barcelona, 1996.

Miembro del Comité Científico Externo del Instituto de Biología Molecular y

Celular del Cáncer, Centro Mixto de la Universidad de Salamanca y el Consejo

Superior de Investigaciones Científicas, 1998-2004.

Miembro del Alto Consejo Científico Consultivo de la Generalitat Valenciana,

desde 1999.

Miembro del Consejo Científico Asesor del Instituto Universitario de

Oncología del Principado de Asturias Obra Social Cajastur, desde 1999.

Miembro del Consejo Asesor del Centro de Biotecnología Animal y Terapia

Génica de la Universidad Autónoma de Barcelona, desde 2003.

Miembro del Consejo Científico Asesor, Centro de Investigación Príncipe

Felipe, Valencia, 2004-08.

Miembro del Comité de selección de Contratos de Investigadores en centros del

Sistema Nacional de Salud, FIS-Instituto de Salud Carlos III, Ministerio de

Sanidad, 1998.

Miembro de Tribunales y Comités de selección de Becas postdoctorales y

Fullbright, del Ministerio de Educación y Ciencia, 2000-2006.

Coordinador de Área y Evaluador de Biología Molecular, Celular y Genética de

las Becas de Formación del Personal Universitario, Ministerio de Educación y

Ciencia, 2000-2006.

Miembro del Comité de selección de Contratos Ramón y Cajal, Min. de Ciencia y

Tecnología, 2001.

Miembro del Comité de selección de becarios de la Fundación Carolina

(Bioquímica), Agencia Española de Cooperación Internacional, Ministerio

Asuntos Exteriores, 2002-2004.

Miembro del Comité evaluador del Certamen Universitario Arquímedes de

Introducción a la generación de conocimiento, Ministerio de Educación y

Ciencia, 2002 y 2005.

Miembro del Jurado del Premio Nacional de Investigación en Biología “Santiago

Ramón y Cajal”, Ministerio de Ciencia y Tecnología, 2002.

Miembro del Jurado del III Premio de la Fundación Francisco Cobos a la

Investigación en Biomedicina, 2002.

Miembro del Jurado de la Convocatoria de Proyectos de Investigación de la

Fundación Científica de la Asociación Española contra el Cáncer, 2002 y 2006.

Miembro de la Comisión de Ciencias de la Salud y Medicina, Fundación Española

para la Ciencia y la Tecnología (Fecyt), Ministerio de Ciencia y Tecnología,

2003-2007.

Miembro de la Comisión del Programa de Biomedicina del Plan Nacional de

I+D+I, Ministerio de Ciencia y Tecnología, 2003 y 2005.

Miembro del Consejo Científico de la Fundación para la Investigación en

Biomedicina del Hospital Universitario Puerta de Hierro de Madrid, 2005-2009.

Evaluador de proyectos de la ANEP, Plan Nacional de I+D, Instituto de Salud

Carlos III-FIS, Junta de Andalucía, Gobierno Vasco, Generalitat de Cataluña

(ICREA), Fundación Areces, Fundación Séneca, UK Biotechnology and Biological

Sciences Research Council (BBSRC).

Miembro del Jurado del Premio Príncipe de Asturias de Investigación

Científica y Técnica, 2006.

Miembro de la Comisión y Coordinador Adjunto de la del Área Biología y

Biomedicina del CSIC, 2006-08.

Miembro del Jurado del Premio de Investigación Biomédica de la Fundación

Banco de Sabadell, 2006-2011. Miembro del Patronato de la Fundación Científica de la Asociación Española

contra el Cáncer, desde 2006.

Miembro de la Comisión Ejecutiva y Coordinador de la Línea de Mecanismos

Moleculares de la Red Temática de Investigación de Centros de Cáncer (RTICC),

Instituto de Salud Carlos III, desde 2007.

Miembro del Jurado del II Premio de Investigación de la Fundación J.

Vilardell, 2008.

Presidente de Tribunal de Oposiciones (Oncología e Inmunología) del Consejo

Superior de Investigaciones Científicas, 2009.

JOSÉ FERNÁNDEZ PIQUERAS

TITULACIÓN

Dr. CC. Biológicas por la Universidad Autónoma de Madrid.

PUESTO DE TRABAJO ACTUAL

Catedrático de Genética de la Universidad Autónoma de Madrid. Departamento

de Biología. Centro de Biología Molecular Severo Ochoa, CSIC/UAM

BREVE CURRICULUM

Profesor de Genética. Universidad Autónoma de Madrid (1978-1986).

Profesor de Genética. Universidad de Granada (1975-1976).

Miembro de las siguientes Sociedades Científicas:

Sociedad Española de Genética (SEG).

Colegio de Biólogos.

OPTIMA.

The American Association for the Advancement of Science.

Asociación Española para el estudio de la Genética Humana (AEGH).

ATANASIO PANDIELLA

TITULACIÓN

Licenciado en Medicina y Cirugía. Universidad de Santiago de Compostela.

PUESTO DE TRABAJO ACTUAL

Vicedirector del Centro de Investigación del Cáncer de Salamanca.

Director del Servicio de Oncofarmacología Traslacional.

Presidente de la Comisión de Cáncer del Instituto de Salud Carlos III.

BREVE CURRICULUM

Secretario científico de la Asociación Española de Investigación en Cáncer

(ASEICA).

XIII Premio de Investigación Fundación Dr. Antonio Esteve.

JOAN GIL SANTANO

TITULACIÓN

Dr. CC. Biológicas por la Universidad de Barcelona.

PUESTO DE TRABAJO ACTUAL

Catedrático de Bioquímica de la Universitat de Barcelona.

BREVE CURRICULUM

Becario postdoctoral Imperial Cancer Research Fund (Londres).

Becario FPI Universitat de Barcelona.

Profesor Ayudante Universitat de Barcelona.

CURRICULUM VITAE

Carlos López Otín es Catedrático de Bioquímica y Biología Molecular en la

Universidad de Oviedo, donde desarrolla su labor docente e investigadora

desde 1987. Su formación académica tuvo lugar en las Universidades de

Zaragoza y Complutense de Madrid, donde se doctoró en el año 1984. Su

labor profesional se ha desarrollado en el Centro Ramón y Cajal de Madrid,

en el Centro de Biología Molecular “Severo Ochoa” de Madrid, y en las

Universidades de Lund-Suecia, Nueva York y Harvard-USA. El trabajo del

grupo que dirige actualmente en la Universidad de Oviedo ha permitido la

identificación de más de 60 nuevos genes humanos y el análisis de sus

funciones en la progresión tumoral y en otros procesos normales y

patológicos, incluyendo los síndromes de envejecimiento prematuro. Entre

sus trabajos más recientes destacan el descubrimiento de un nuevo

mecanismo de supresión tumoral mediado por proteasas y el diseño de un

tratamiento para pacientes con progeria. Además, su grupo de investigación

ha contribuido a la anotación y secuenciación de los genomas humanos, del

chimpancé y de diversos organismos modelo, estudios que han permitido

definir nuevas claves de la evolución humana. Es académico de número de

la Real Academia de Ciencias y de la Academia Europea, y ha recibido

diversos galardones y distinciones, incluyendo el Premio Europeo FEBS de

Bioquímica, el Premio Carmen y Severo Ochoa de Biología Molecular, y el

Premio Jaime I de Investigación.

BENILDE JIMÉNEZ CUENCA

TITULACIÓN

Dra. CC. Químicas por la Universidad Autónoma de Madrid.

PUESTO DE TRABAJO ACTUAL

Profesora de Bioquímica. Facultad de Medicina. Universidad Autónoma de

Madrid.

BREVE CURRICULUM

Profesora asociada. Universidad Autónoma de Madrid (1996-2001).

Becaria postdoctoral. Lurie Cancer Center, Chicago, USA (1995-1997).

Ayudante LRU. Universidad Autónoma de Madrid (1990-1995).

Becaria postdoctoral. U- 248 INSERM, París, Francia (1989-1990).

Becaria postdoctoral. Universidad Autónoma de Madrid (1985-1989).

MARIANO BARBACID

TITULACIÓN

Doctor en CC. Químicas.

PUESTO DE TRABAJO ACTUAL

Jefe del Grupo de Oncología Experimental del Centro Nacional de

Investigaciones Oncológicas.

BREVE CURRICULUM

NCI Campus in Frederick, Meryland.

Vicepresidente del area de Descubrimiento de Drogas Oncológicas en Bristol

Myers-Squibb Pharmaceutical Research Institute in Princeton.

MANUEL PERUCHO

Curriculum Vitae

Birthdate and Place: February 17, 1948 La Roda (Albacete), Spain Marital Status: Married, four children. Nationality: Spanish Academic Degrees:

Master in Biological Sciences University of Madrid, Spain (1971) Ph.D. in Biological Sciences University of Madrid, Spain (1976)

Research Experience:

1972-1976 Ph.D. Department of Molecular Biology, Institute Gregorio Marañon, Madrid. Comparative analysis of DNA-binding proteins in cultured normal versus transformed mammalian cells. Physico-chemical and biological characterization of a single-strand DNA-binding protein purified from transformed hamster fibroblasts.

1977-1978 Postdoctoral work in the Max-Planck-Institut für Molekulare Genetik, Berlin. Isolation and biochemical characterization of the messenger RNA for the tissue-specific histone H5 from immature chicken erythrocytes.

1979-1980 Postdoctoral work in Cold Spring Harbor Laboratory. Studies on the mechanisms of DNA-mediated gene transfer in cultured animal cells, and its application to the isolation of higher eukaryotic genes coding for selectable markers.

1981-1982 Staff Investigator at Cold Spring Harbor Laboratory. Molecular Genetics of Malignancy: detection of human oncogenes by DNA-mediated gene transfer in animal cells.

1982-1987 Assistant Professor, Department of Biochemistry, State University of New York at Stony Brook. Isolation and characterization of ras oncogenes from human tumors. Regulation of ras oncogene expression.

1987-1988 Associate Professor, Department of Biochemistry, State University of New York at Stony Brook. Molecular diagnosis of mutant ras oncogenes in human cancer.

1988-1995 Research Program Director, California Institute of Biological Research, La Jolla, California. Role of oncogene activation in human tumorigenesis. Detection of somatic genetic alterations in gastrointestinal tumors. Etiology of oncogenic mutations

1995-2007 Professor and Program Director, Cancer Genetics and Epigenetics, The Burnham Institute for Medical Research, La Jolla, California. Molecular pathogenesis of cancer of the microsatellite mutator phenotype. Genomic instability in gastrointestinal cancer.

1997-present. Adjunct Professor, University California San Diego (UCSD), Depts. of Medicine and Molecular Pathology.

1999-2001 Visiting Professor, University Pompeu Fabra, Barcelona.

2002-2008 Visiting Professor, University Autonoma, Barcelona.

2004-2008 Associated Investigator, Fundación Investigación Sanitaria Castilla-La Mancha (FISCAM).

2004-2009 Member Advisory Board, Instituto Canario Investigación Cancer (ICIC).

2007-2012 Professor and Program Co-Director, Tumor Development Program. Sanford-Burnham Medical Resaerch Institute (SBMRI) La Jolla, California. Epigenetics of cancer.

2012-present. Adjunct Professor. SBMRI, La Jolla, California.

2008-present Director, Institute of Predictive and Personalized Medicine of Cancer (IMPPC). Badalona, Barcelona, Spain.

HONORS (Awards, Fellowships, Honorary Degrees, etc.) • Predoctoral fellowship from the Juan March Foundation, Madrid. (1975-1976). • Ph.D. degree with honors. University of Madrid. (1976). • Postdoctoral fellowship from the Max-Planck-Institut für Molekulare Genetik. Berlin. (1977-1978). • Postdoctoral fellowship from the Committee for the Scientific and Technological Cooperation between

Spain and USA. Cold Spring Harbor, New York (1979-1980). • Recipient of the William and Florence Catacosinos Award on Cancer Research. State University of

New York at Stony Brook. December 1981. • Co-recipient (with Drs. M. Barbacid and A. Pellicer) of the 1984 Francisco Duran-Reynals Prize for

basic research on cancer. Barcelona, Spain. May 1984. • Medal on Cancer Research awarded by the National Cancer Center. Tokyo, Japan. March 1985. • Special Recognition for Teaching Excellence by the Office of Undergraduate Studies, State University

of New York at Stony Brook. 1986. • Co-recipient (with Drs. M. Barbacid and A. Pellicer) of the Marques de Valdecilla Foundation First

Award for basic research on cancer. Santander, Spain. 1987. • Citation of a research article published in Nature on c-K-ras activation during human colon

tumorigenesis in the 1988 Year Book of Cancer, R.C. Hickey, ed., Times Mirror Books. Year Book Medical Publishers.

• Front cover of Cancer Research, June 1, 1988, vol. 48, no. 11. Review on the research article on ras

oncogenes in colon cancer. • Citation in the Accomplishments for FY 1993 of the Cancer Diagnosis Branch of the National Cancer

Institute, NIH. November 1993. • Citation in the Special Section Challenges for 1994: "A Joycean Mutation. Researchers discover a

new mechanism for cancer". Scientific American, December 1993, pg. 47. • Front cover of the International Journal Oncology, Vol 4, number 1, January 1994. • Hot paper citation in The Scientist. February 20, 1995. Pag. 15. • Merit Award from the National Cancer Institute for NIH grant CA 63585. June 1999. • Hot paper citation in The Scientist. October 25, 1999. Pag. 16. • Gold medal from the Academia de Medicina y Cirujia, Murcia, Spain. May 2001. • Atlantic Prize for Cancer Research (Premio Atlantico de investigacion del Cancer), awarded by the

Canarian Institute for Cancer Research (Instituto Canario de Investigacion del Cancer, ICIC). Las Palmas, Canary Islands, March 2003.

• Recipient of the 2003 American Association for Cancer Research-National Foundation for Cancer

Research (AACR-NFCR) Professorship in Basic Cancer Research. April 2003. • Doctor Honoris Causa by the University Pablo de Olavide de Sevilla. May 2005.

MEETINGS AND COURSES ORGANIZED 1. First Stony Brook Symposium. Masayori Inouye, organizer. M. Perucho, organizer and chairman of

Workshop on Cellular Tumor Genes, Stony Brook, NY 1983. 2. International Workshop on "Molecular Diagnosis of Cancer". Foundation Juan March. M. Perucho

and P. Garcia Barreno, organizers. Madrid, Spain. November 1989. 3. Course on "Gene transfer, oncogenes and molecular genetics of cancer". Foundation Juan March.

M. Perucho and J. Ortin, organizers. Siguenza, Spain. July 1990. 4. AMBO International Training Course on "Detection of DNA Aberrations in Cancer Cells" (Lectures

and Laboratory classes). T. Sekiya, S. Nishimura, S. Takayama, organizers. M. Perucho, member of invited teaching staff. Tokyo, Japan. March 1991.

5. NATO Advanced Research Workshop on "The Super-family of Ras Related Genes" University of Crete. D. Spandidos, A. Balmain, P. Chardin, J.C. Lacal, C. Marshall, F. McCormick and M. Perucho, organizers. Heraklion, Crete, Greece. May 1991.

6. Lecture Course on the "Polymerase Chain Reaction". Foundation Juan March. M. Perucho and E. Martinez-Salas, organizers. Cuenca, Spain. May 1991.

7. International Symposium on "Human Oncogenes: The Second Decade". Foundation Ramon Areces. M. Perucho, A. Pellicer and J.C. Lacal, Organizers. Madrid, Spain. April 1992.

8. Universidad Complutense of Madrid Summer Course "Biological Complexity: from Chaos to Cancer". M. Perucho and E. Cerda, Organizers. El Escorial, July 4-8, 1994.

9. Universidad Menendez Pelayo Santander. Course “Biologia y Genetica del Cancer. Marcadores geneticos y moleculares”. F. Bonilla and M. Perucho, Organizers. Santander, July 27-31, 1998.

10. Universidad Complutense of Madrid Summer Course "From the selfish gene to the human brain". M. Perucho, Organizer. El Escorial, August 3-7, 1998.

11. The Burnham Institute 21st. Annual Symposium: “Genome Dynamics. Somatic Mutation and Hypermutation in Normal and Cancer Cells”. M. Perucho, Conference Chairperson. La Jolla, March 25-26, 1999.

12. Universidad Autónoma de Barcelona (UAB). Postgraduate course “Mecanismos moleculares del cáncer. Cánceres de colon, mama y prostata”. E. Escrich and M. Perucho, directors. Barcelona, March 17-22, 2003.

13. Universidad Internacional de Andalucia Summer Course "Genes, Oncogenes y Memes: Aventuras con la doble hélice". M. Perucho, Director. Baeza, September 8-12, 2003.

14. UAB. Postgrad. course “Mecanismos moleculares del cáncer. Cánceres de colon, mama y prostata”. E. Escrich and M. Perucho, dirs. Barcelona, March 15-20, 2004.

15. Fundación para la Investigación Sanitaria en Castilla-La Mancha (FISCAM), Summer Workshop “Genes, Genoma y Cáncer: de la doble hélice a la medicina predictiva”. M. Perucho, director. Toledo, 28-30 September, 2004.

16. UAB. Postgrad. course “Mecanismos moleculares del cáncer. Cánceres de colon, mama y prostata”. E. Escrich and M. Perucho, dirs. Barcelona, March 14-19, 2005.

17. Universidad de Sevilla. Graduate course “Alteraciones genéticas y epigenéticas en el cancer”. M. Perucho, director. Sevilla, May 20-25, 2005.

18. Fundación Investigación Sanitaria Castilla-La Mancha (FISCAM), Summer Workshop “Genes y Cáncer: desde la doble hélice a la biología postgenómica”. M. Perucho, director. Cuenca, 18-21 Julio, 2005.

19. UAB. Postgrad. course “Mecanismos moleculares del cáncer. Cánceres de colon, mama y prostata”. E. Escrich and M. Perucho, dirs. Barcelona, June, 2006.

20. Universidad de Sevilla. Graduate course “La genética y epigenética del cancer”. M. Perucho, director. Sevilla, March 2008.

21. Institute of Predictive and Personalized Mediciene of Cancer (IMPPC). “Symposium on Genomics, Epigenomics and Predictive Medicine of Cancer”. M. Perucho, Organizer. Barcelona, Hotel Colon, December 11, 2009.

22. Institute of Predictive and Personalized Mediciene of Cancer (IMPPC). “First Annual IMPPC Conference on Genetics, Epigenetics and Cancer Prediction”. M. Perucho, & M. A. Peinado, Organizers. Barcelona, Hotel Colon, March 18-19, 2010.

23. New York Academy of Sciences. “Towards Persnalized Cancer Medicine”. M. Perucho, Co-organizer. Barcelona, May 19-21, 2010.

24. IMPPC Worshop on Biobanking inPredictive Medicine. M. Perucho, & R. de Cid, Organizers. Barcelona, Hotel Colon, April 24, 2012.

SERVICE IN ADVISORY COMMITTEES AND EDITORIAL TASKS:

• Member of special review committee, National Cancer Institute. Site visit to Children's Cancer Research Center. Philadelphia, PA, July 10-12, 1983 (2PO1 CA14489-10).

• Member of special study section, National Cancer Institute. RFA No. NIH-NCI-DCBR-BD-84-21, "Application of Recombinant DNA Technology of Diagnosis of Cancer". Washington, DC, February 19, 1985.

• Member of Advisory Committee on Cell and Developmental Biology, American Cancer Society. New York, NY, June 10-11, 1985.

• Member of special review committee, National Cancer Institute. Site visit to Johns Hopkins University. Baltimore, MD, April 7-9, 1986 (PO1 CA42762).

• Member of special review committee, National Cancer Institute. Site visit to University of Arizona, Tucson, AZ, June 9-11, 1986 (PO1 CA41183).

• Chairman, Selection Committee for research positions of the Spanish Consejo Superior de Investigaciones Científicas (CSIC) in Biotechnology, Cellular Pathology and Virology, for the National Center of Virology, Majadahonda, Madrid, Spain, November 1989.

• Member of special review committee, National Cancer Institute. Site visit to New England Deaconess Hospital - Dana Farber, Boston, MA, March 26-28, l990 (PO1 CA 44704-04).

• Ad-hoc member, Pathology B Study Section, NIH. February and June 1990.

• Editor, Critical Reviews in Oncogenesis, CRC Press, Inc., Boca Raton, FL. 1989-1995.

• Member, Pathology B Study Section, NIH. 1995-1999.

• Member of special review committee, National Cancer Institute. Site visit to Jefferson University-Kimmel Cancer Institute, Philadelphia, PA. 04/13-04/15/98 (PO1 CA 76259-01A1).

• Member of special study section, National Cancer Institute. PAR 98-066 & PAR 98-067. “Innovative technology for the molecular analysis of cancer”. Washington, November 18-20, 1998.

• Member of Specialized Programs of Research Excellence (SPOREs) Review Panel, National Cancer Institute. ZCA1-GRB-V(J1). SPORE applications in GI cancers. San Diego, CA, October 13-14, 2003.

• Member, Cancer and Leukemia Group B (CALGB) GI, Solid Tumor Correlative Sciences. 1999-present.

• Member, National Cancer Institute Committee on Specimen Resources. 1998- present.

• Member of the Editorial Board of the International Journal of Oncology. 1993-present.

• Member of the Editorial Board of the International Journal of Cancer. 1997-present.

• Member of the Editorial Board of BioMed Central Medicine. 2001-present.

• Member of the Editorial Board of Cancer Science. 2003-present.

• Member of Advisory panel for Fundacion Echevarne, National Prizes in Oncology, 1995, 1999 and 2003.

• Reviewer of grants from the following agencies:

National Institutes of Health (NIH) National Science Foundation (NSF); The City University of New York (PSC-CUNY); March of Dimes Foundation; Israel Academy of Sciences and Humanities; Spanish Comision Interministerial de Ciencia y

Tecnologia (CICT); Veterans Administration;

Dutch Cancer Society; Council for Medical & Health Res. Netherlands Medical Research Council of Canada; Associazione Italiana per la Ricerca sul Cancro; The Barts & The London Charitable Foundation; Fundacion Cientifica de la Asociacion Española

Contra el Cancer Spanish Ministry Science & Education, program

CONSOLIDER.

• Reviewer of articles for the Journals:

Science; Nature Genetics; Nature Medicine; Cancer Cell; Molecular and Cellular Biology; Proceedings of the National Academy of Sciences US. PNAS; Cancer Research; Clinical Cancer Research; Molecular Cancer Research; Oncogene; Oncogene Research; Advances in Cancer Research; American Journal Pathology; Biochimica Biophysica Acta; Biological Chemistry; BioMed Central; Biomed Central Cancer; Biotechniques; British Journal of Cancer; Cancer Epidemiol. Biomarkers & Prevention; Cancer Letters; Carcinogenesis; Cell Death & Differentiation; Cell Growth & Differentiation; Cytogenetics & Cell Genetics; European Journal of Cancer;

Gastroenterology; Genes, Chromosomes & Cancer; Gut; Human Molecular Genetics; Human Mutation; International Journal of Cancer; International Journal of Oncology International Journal of Pancreatology; Japanese Journal Cancer Research; Journal of Bacteriology; Journal of Biological Chemistry; Journal of Cell Biology; Journal of Clinical Investigation; Journal of Medical Genetics Journal of Molecular Biology; Journal of the National Cancer Institute; Journal of Virology; Laboratory Investigation; Leukemia Research; Mammalian Genome. Molecular & Cellular Probes; Molecular & General Genetics; Molecular Carcinogenesis; Nucleic Acids Research; Oncology Research; PCR Methods & Applications; Virology;

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PREVIOUS SOURCES OF RESEARCH SUPPORT: 1. New York Health Research council. (6/82 - 1/83). M. Perucho, Principal Investigator.

"Tumor Genes from Human Lung Cancer." Award amount: $7,500. 2. Biomedical Research Support (NIH). (11/81- 3/83).

M. Perucho, Principal Investigator. "Isolation of Tumor Genes from Human Lung Carcinomas." Award amount: $10,000 3. National Institutes of Health (NIH), National Cancer Institute.

(NCI). Grant R01 CA 33021-1to 5 (12/81 - 1/86). M. Perucho, Principal Investigator. "Isolation of Tumor Genes from Human Lung Carcinomas." Award amount: $588,758. 4. American Cancer Society.

Grant NP-402 (1/83 - 12/84). M. Perucho, Principal Investigator. "Isolation of Tumor Genes from Human Lung Carcinomas." Award amount: $164,375. (Declined). 5. Biomedical Research Support (NIH). (4/84 - 3/85). M. Perucho, Principal Investigator (Fellowship for Dr. E. Winter).

"Expression of the c-K-ras Oncogene from Human Lung Carcinomas." Award amount: $8,400. 6. NIH, NCI grant R01 CA 38579-1 to 4 (1/85- 12/87). M. Perucho, Principal Investigator. "Molecular Genetics of mutant ras Oncogenes in Human Tumors." Award amount: $385,206. 7. NIH, NCI grant R01 CA 33021-6 to 11. (2/86 - 1/91). M. Perucho, Principal Investigator. "Expression of the Human c-K-ras Gene. Award amount: $602,148. 8. American Cancer Society. Grant MV-291. (1/86 - 12/87). M. Perucho, Principal Investigator. "Expression of the Human c-K-ras Gene. Award amount: $160,000. (Declined). 9. Toyo Jozo Ltd. (5/83 - 4/87). M. Perucho, and Masayori Inouye, Co-Principal Investigators.

"Cloning and Expression of the Protein Encoded by the Human Lung Carcinoma Tumor Gene." Award amount: $248,000.

10. New York State Science and Technology Foundation. (9/83 - 6/86). M. Perucho and Masayori Inouye, Co-Principal Investigators. "Genetic Engineering, Immundiagnostics and Drug Development." Award amount: $65,210.

11. Center of Biotechnology, SUNY at Stony Brook. (7/85 - 6/87). M. Inouye, Principal Investigator, M. Perucho, Co-Principal Investigator.

"Development and Application of RNA Repressors for Regulating Specific Genes in Eukaryotes

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and Prokaryotes." Award amount; $18,000. 12. NIH, NCI RO1 CA38579-5 to 9 (1/1/88-2/28/93) M. Perucho, Principal Investigator

"Mutant ras Oncogenes in Human Tumors" Award amount: $548,412. 13. NIH, NCI RO1 CA33021-6 to 13 (2/91-2/94)

M. Perucho, Principal Investigator "Expression of the Human c-K-ras Gene"

Award amount: $417,664 14. NIH MAO N01-CN-15340-02 (subcontract) (9/30/92 - 9/29/95) William E. Grizzle, Principal Investigator, "Early Detection Research Network MAO II."

M. Perucho, Co-Principal Investigator. "Oncogene and Tumor Suppressor Gene Mutations in Prostate Cancer". Award amount for subcontract $120,192. 15. NIH, NCI R01 CA63585 (05/01/94-02/28/99) M. Perucho, Principal Investigator. "Molecular Pathogenesis of Cancer of the Mutator Phenotype". Award amount: $1.478,419 direct costs. 16. USAMRMC BCRP 972661 (10/01/98-09/30/2000) M. Perucho, Principal Investigator. “A new approach for the immunodiagnostics of breast cancer by random peptide phage display”. Award amount: $140,240 direct costs. 17. NIH, NCI RO1 CA38579 (08/17/93-02/28/2004) M. Perucho, Principal Investigator "Somatic genetic alterations in gastrointestinal tumors" Award amount: $958,784 direct costs. (last year: $170,085). 18. NIH, NCI R01 CA63585 (03/01/99-04/31/2004) M. Perucho, Principal Investigator. "Molecular Pathogenesis of Cancer of the Mutator Phenotype". Award amount: $1.901,514 direct costs. (last year: $342,000) 19. NIH/NCI R01 CA098818-03 07/01/03 – 06/30/10

M. Perucho, Principal Investigator Microsatellite instability and cancer gene expression.

Award amount: $1.125,000 direct costs.

20. National Institutes of Health (NIH)/National Cancer Institute (NCI) 05/01/2004 – 04/30/11 R37 (Merit Award) CA63585-13 M. Perucho, Principal Investigator Molecular pathogenesis of cancer of the mutator phenotype.

Award amount: $2.125,000 direct costs.

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CURRENT SOURCES OF RESEARCH SUPPORT:

1. Fondo Investigación Sanitaria (FIS)/Instituto de Salud Carlos III (ISCIII) 01/01/2010 – 31/12/2012 M. Perucho, Principal Investigator. “Genetic and Epigenetic Alterations in the ADMTS Gene Family in Human Cancer”. Award amount: 370,865 Euros.

2. Ministry of Health and Science Instituto de Salud Carlos III (ISCIII) (ADE10/00026 2011 -- 2016 M. Perucho, Principal Investigator. Start-up and Potentiation of the Program Genomics & Epigenomics of Cancer Prediction Award amount: 6.000,000 Euros.

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PUBLICATIONS

More than 13,340 citations, averaging 102.7 citations per article (h-index of 46) as of 2010.

1. Perucho, M., Salas, J. and Salas, M.L. (1977) Identification of the mammalian DNA-binding protein P8 as glyceraldehyde-3-phosphate dehydrogenase. Eur. J. Biochem. 81, 557-562.

2. Perucho, M., Molgaard, H.V., Shevack, A., Pataryas, T. and Ruiz-Carrillo, A. (1979) An improved

method for the preparation of undegraded polysomes and active messenger RNA from immature chicken erythrocytes. Anal. Biochem. 98, 464-471.

3. Perucho, M., Salas, J. and Salas, M.L. (1980) Study of the interaction of glyceraldehyde-3-

phosphate dehydrogenase with DNA. Biochem. Biophys. Acta 606, 181-195. 4. Molgaard, H.V., Perucho, M. and Ruiz-Carrillo, A. (1980) Histone H5 messenger RNA is

polyadenylated. Nature 283, 502-504. 5. Wigler, M., Perucho, M., Kurtz, D., Dana, S., Pellicer, A., Axel, R. and Silverstein, S. (1980)

Transformation of mammalian cells with an amplifiable dominant acting gene. Proc. Natl. Acad. Sci. USA 77, 3567-3570.

6. Perucho, M., Hanahan, D., Lipsich, L. and Wigler, M. (1980) Isolation of the chicken thymidine

kinase gene by plasmid rescue. Nature 285, 207-210. 7. Perucho, M., Hanahan, D. and Wigler, M. (1980) Mechanisms of DNA-mediated transformation in

animal cells. 9th Annual ICN-UCLA Symposia. Animal virus genetics. B. Fields and R. Jaenish, eds. Academic Press, Inc. pp. 155-169.

8. Perucho, M., Hanahan, D. and Wigler, M. (1980) Genetic and physical linkage of exogenous

sequences in transformed cells. Cell 22, 309-317. 9. Perucho, M. and Wigler, M. (1981) Linkage and expression of foreign DNA in cultured animal

cells. Cold Spring Harb. Symp. Quant. Biol. 45, 829-838. 10. Wigler, M., Levy, M. and Perucho, M. (1981) The somatic replication of DNA methylation. Cell 24,

33-40. 11. Perucho, M., Goldfarb, M., Shimizu, M., Lama, C., Fogh, J. & Wigler, M. (1981) Human-tumor-

derived cell lines contain common & different transforming genes. Cell 27, 467-476. 12. Perucho, M., Molgaard, H.V. and Ruiz-Carrillo, A. (1982) Enrichment of histone H5-synthesizing

polysomes by indirect immunoadsorption. Purification of H5 mRNA. J. Biol. Chem. 257, 958-963. 13. Goldfarb, M., Shimizu, K., Perucho, M. and Wigler, M. (1982) Isolation and preliminary

characterization of a human transforming gene from T24 bladder carcinoma cells. Nature 296, 404-409.

14. Shimizu, K., Goldfarb, M., Perucho, M. and Wigler, M. (1983) Isolation and preliminary

characterization of the transforming gene of a human neuroblastoma cell line. Proc. Natl. Acad. Sci. USA 80, 383-387.

15. Shimizu, M., Goldfarb, M., Suard, Y., Perucho, M., Li, Y., Kamata, T., Feramisco, J., Stavnezer, E., Fogh, J. and Wigler, M.H. (1983) Three human transforming genes are related to the viral ras oncogenes. Proc. Natl. Acad. Sci. USA 80, 2112-2116.

16. Wigler, M., Goldfarb, M., Shimizu, K., Perucho, M., Suard, Y., Fasano, O., Taparowsky, E. and Fogh, J. (1983) Identification, isolation and characterization of three distinct human transforming genes. In "Genes and Proteins in Oncogenesis," I.B. Weinstein and H.J. Vogel, eds. Academic Press, New York. pp. 285-292.

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17. Wigler, M., Shimizu, K., Perucho, M., Goldfarb, M. and Fogh, J. (1983) Identification, isolation and characterization of human transforming genes. In "Nucleic Acid Research: Future Developments," K. Mizobuchi, I. Watanabe, and T. Watson, eds. Academic Press, New York. pp. 377-392.

18. Nakano, H., Yamamoto, F., Neville, C., Evans, D., Mizuno, T. & Perucho, M. (1984) Isolation of

transforming sequences of two human lung carcinomas: Structural & functional analysis of the activated c-K-ras oncogenes. Proc. Natl. Acad. Sci. USA 81, 71-75.

19. Nakano, H., Neville, C., Yamamoto, F., Garcia. J.L., Fogh, J. and Perucho, M. (1984) Structure

and mechanisms of activation of the c-K-ras oncogene from two human lung tumors. Cold Spring Harbor Conferences on Cell Proliferation and Cancer, Vol. XI: The Cancer Cell, Oncogenes and Viral Genes. pp. 447-454.

20. Yamamoto, F. and Perucho, M. (1984) Activation of a human c-K-ras oncogene. Nucl. Acids Res.

12, 8873-8885. 21. Yamamoto, F., Nakano, H., Neville, C. and Perucho, M. (1985) Structure and mechanisms of

activation of c-K-ras oncogenes in human lung cancer. Progress in Medical Virology 32, 101-114

22. Perucho, M. and Esteban, M. (1985) Inhibitory effect of interferon on the genetic and oncogenic

transformation by viral and cellular genes. J. Virol. 54, 229-232. 23. Tamaoki, T., Mizukami, T., Perucho, M. and Nakano, H. (1985) Expression of intact Ki-ras p21

protein in Escherichia coli. Biochem. Biophys. Res. Comm. 132, 126-133. 24. Winter, E., Yamamoto, F., Almoguera, C. and Perucho, M. (1985) A method to detect and

characterize point mutations in transcribed genes: Amplification and overexpression of the mutant c-K-ras allele in human tumor cells. Proc. Natl. Acad. Sci. USA 82, 7575-7579.

25. Winter, E. & Perucho, M. (1986) Oncogene amplification during tumorigenesis of established rat

fibroblasts reversibly transformed by activated human ras oncogenes. Mol. Cell. Biol. 6, 2562-2570. 26. Perucho, M. and Massague, J. (1986) Reversible induction of transforming growth factor alpha by

human ras oncogenes. J. Tumor Markers Oncology 1, 81-91. 27. Jordano, J. and Perucho, M. (1986) Chromatin structure of the promoter region of the human c-K-

ras gene. Nucl. Acids Res. 14, 7361-7378. 28. Nakano, E.T., Rao, M.M., Perucho, M. and Inouye, M. (1986) Expression of the Kirsten ras viral

and human proteins in Escherichia coli. J. Virol. 61 302-307. 29. Forrester, K., Almoguera, C., Han, J., Grizzle, W.E. & Perucho, M. (1987) Detection of high

incidence of K-ras oncogenes during human colon tumorigenesis. Nature 327, 298-303. 30. Kahn, S., Yamamoto, F., Almoguera, C., Winter, E., Forrester, K., Jordano, J. and Perucho, M.

(1987) The c-K-ras oncogene and human cancer. Anticancer Research 7, 639-652. 31. Forrester, K., Almoguera, C., Jordano, J., Grizzle, W.E. and Perucho, M. (1987) High incidence of

c-K-ras oncogenes in human colon cancer detected by the RNAse a mismatch cleavage method. J. Tumor Markers Oncology 2, 113-123.

32. Almoguera, C., Forrester, K., Winter, E., Lama, C. and Perucho, M. (1987) Activated ras genes in

pulmonary carcinomas. Proceedings of the International Conference on Hormones, Growth Factors and Oncogenes in Pulmonary Carcinoma. In "Lung Cancer".

33. Jordano, J. and Perucho, M. (1988) Initial characterization of a potential transcriptional enhancer for the human c-K-ras gene. Oncogene 2, 359-366.

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34. Yamamoto, F. and Perucho, M. (1988) Characterization of the human c-K-ras gene promoter. Oncogene Res. 3, 125-138.

35. Lopez-Galindez, C., Lopez, J.A., Melero, J.A., Dela Fuente, L., Martinez, C., Ortin, J. and

Perucho, M. (1988) Analysis of genetic variability and mapping of point mutations in influenza virus by the RNAse A mismatch cleavage method. Proc. Natl. Acad. Sci. USA 85, 3522-3526.

36. Almoguera, C., Shibata, D., Forrester, K., Martin, J., Arnheim, N. and Perucho, M. (1988) Most

human carcinomas of the exocrine pancreas contain mutant c-K-ras genes. Cell 53, 549-554. 37. Forrester, K., Almoguera, C., Lama, C., Dunitz, J., Kawanishi, H., Grizzle, W.E. and Perucho, M.

(1990) Expression and mutational activation of the c-K-ras oncogene in human colo-rectal adenomas and carcinomas. In "Familial Adenomatous Polyposis," L. Herrera, ed. Alan R. Liss, Inc., New York. pp. 337-346.

38. Perucho, M., Forrester, K., Almoguera, C., Kahn, S., Lama, C., Shibata, D., Arnheim, N. and

Grizzle, W.E. (1989) Expression and mutational activation of the c-Ki-ras gene in human carcinomas. Cold Spring Harbor Laboratory Cancer Cells, "Molecular Diagnostics of Human Cancer" , 7 pp 137-141.

39. Almoguera, C., Forrester, K. and Perucho, M. (1989) Application of the Polymerase Chain

Reaction for the detection of single-base substitutions by the RNAse A mismatch cleavage method. In "Current Communications in Molecular Biology," Polymerase Chain Reaction (Erlich, H.A., Gibbs, R. and Kazazian, H.H., eds.). Cold Spring Harbor Laboratory. pp 37-41.

40. Perucho, M. (l989) Detection of single-base substitutions with RNAse A mismatch cleavage

method. Strategies in Molecular Biology 2, 37-41. 41. Shibata, D., Almoguera, C., Forrester, K., Dunitz, J., Martin, S.E., Cosgrove, M.M., Perucho, M.

and Arnheim, N. (1990) Detection of c-K-ras mutations in fine needle aspirates from human pancreatic adenocarcinomas. Cancer Res. 50, 1279-1283.

42. Shibata, D., Capella, G. and Perucho, M. (l990) Mutational activation of the c-K-ras gene in

human pancreatic carcinoma. Bailliere's Clinical Gastroenterology 4, 151-169. 43. Perucho, M., Capella, G. and Shibata, D. (1990) Oncogene activation in human pancreatic

carcinoma. Proceedings of the American Association for Cancer Research 31, 19:478-479. 44. Lopez-Galindez, C., Rojas, J.M., Najera, R., Richman, D.D. and Perucho, M. (l991)

Characteriztion of genetic variation and AZT resistance mutations of HIV by the RNAse A mismatch cleavage method. Proc. Natl. Acad. Sci. USA 88, 4280-4284.

45. Viola, M.V., Chen, J., Fromowitz, F., Finkel, G., Compton, C. and Perucho, M. (1991) ras mutation

in precancerous cells in ulcerative colitis. In "Dysplasia & Cancer," Robert Riddle, ed., Elseiver Science Publishing Co., New York, NY. pp. 153-159.

46. Capella, G., Lluis, F., Sancho, J. and Perucho, M. (1991) Activation of the c-K-ras gene in the

colon adenoma-carcinoma sequence. Oncology 41, pp. 459-461. 47. Capella, G., Cronauer-Mitra, S., Peinado, M.A. and Perucho, M. (l991) Frequency and spectrum

of mutations at codons 12 and 13 of the c-K-ras gene in human tumors. Environm. Health Perspectives 93, pp. 125-131.

48. Corominas, M., Perucho, M., Newcomb, E.W. & Pellicer, A. (1991) Differential expression of the

normal and mutated K-ras alleles in chemically induced thymic lymphomas. Cancer Res. 51 5129-5133.

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49. Peinado, M.A., and Perucho, M. (1991) Taq polymerase cycling sequencing of PCR amplified DNA. Fundacion Juan March. Serie Universitaria pp. 78-86.

50. Peinado, M.A., Malkhosyan, S., Velazquez, A., and Perucho, M. (1992) Isolation and characterization of allelic losses and gains in colorectal tumors by arbitrarily primed polymerase chain reaction. Proc. Natl. Acad. Sci. USA. 89, 10065-10069.

51. Peinado, M.A., Fernandez-Renart, M., Capella, G., Wilson, L. and Perucho, M. (1993). Mutations

in the p53 suppressor gene do not correlate with c-K-ras oncogene mutations in colorectal cancer. International J. Oncology, 2, 123-134.

52. Schaeffer, J. Capella, G., Peinado, M.A., Fernandez-Renart, M., and Perucho, M. (1993)

Comparative analysis of genetic alterations in pancreatic and other carcinomas. International J. of Pancreatology 14, 75-77.

53. Ionov, Y., Peinado, M.A., Malkhosyan, S., Shibata, D. and Perucho, M. (1993) Ubiquitous somatic

mutations in simple repeated sequences reveal a new mechanism for colonic carcinogenesis. Nature, 363, 558-561.

54. Shibata, D., Schaeffer, J., Li, Z.-H., Capella, G. and Perucho, M. (1993) Genetic heterogeneity of

the c-K-ras locus in colorectal adenomas but not adenocarcinomas. J. Natl. Cancer Institute 85, 1058-1063.

55. Perucho, M. (1994). PCR and Cancer Diagnostics: Detection and characterization of single point

mutations in oncogenes and antioncogenes. In "The Polymerase Chain Reaction". Mullis, K.B., Ferre, F. and Gibbs, R.A. Eds. Birkhauser, Spinger-Verlag. 369-394.

56. Shibata, D., Peinado, M.A., Ionov, Y., Malkhosyan, S. and Perucho, M. (1994). Genomic instability

in repeated sequences is an early somatic event in colorectal tumorigenesis that persists after transformation. Nature Genetics, 6, 273-281.

57. Berrozpe, G., Schaeffer, J., Peinado, M. A., Real, F. X. and Perucho, M. (1994). Comparative

analysis of mutations in the p53 and K-ras genes in pancreatic cancer. International Journal of Cancer. 58, 185-191.

58. Perucho, M., Schaeffer, J., Velazquez, A., Berrozpe, G., and Capella, G. (1994). Genetic

alterations. In "Facing the Pancreatic Dilemma". Proceedings of the Verona 93 / International Symposium on Pancreatic Disease. Springer-Verlag. 226-238.

59. Perucho, M., Peinado, M. A., Velazquez, A., Mok, S. M. and Berkowitz, R. S. Somatic mutations in

oncogenes and antioncogenes: the molecular basis of gynecological oncology. Proc. 8th Intern. Meeting of Gynecological Oncology, Barcelona, 1993.

60. Umar, A., Boyer, J. C., Thomas, D.C., Nguyen, D.C., Risinger, J.I., Boyd, J., Ionov, Y., Perucho, M. and Kunkel, T. (1994) Defective mismatch Repair in Extracts of Colorectal and Endometrial Cancer Cell Lines Exhibiting Microsatellite Instability. J. Biol. Chem. 269, 14367-14370.

61. Perucho, M., Welsh, J., Peinado, M. A., Ionov, Y. and McClelland, M. (1995). Fingerprinting of DNA and RNA by arbitrarily primed PCR: applications in cancer research. Methods in Enzymology. 254, 275-290.

62. Najera, I., Richman, D.D., Olivares, I., Rojas, J.M., Peinado, M.A., Perucho, M., Najera, R., and Lopez-Galindez, C. (1994). Natural occurrence of drug resistance mutations in the reverse transcriptase of human immunodeficiency virus type 1 isolates. AIDS Res. and Human Retroviruses. 10, 1479-1488.

63. Welsh, J., McClelland, M., Perucho, M and Peinado, M. (1995). Fingerprinting of DNA and RNA

using arbitrarily primed PCR. In PCR 2, a Practical Approach. D. Howes, I.D. Glover, Eds Oxford University Press. McPherson, M.J., Hames, B.D. and Taylor, G.R. Eds. 197-218.

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64. Kahn, S.M., Jiang, W., Weinstein, I.B. and Perucho, M. Diagnostic detection of mutant ras genes

in minor cell populations. (1995). Methods in Enzymology. 255, 452-464. 65. Perucho, M., Peinado, M. A., Ionov, Y., Casares, S., Malkhosyan, S. and Stanbridge, E. (1994).

Defects in replication fidelity of simple repeated sequences reveal a new mutator mechanism for oncogenesis. Cold Spring Harbor Sympos. Quant. Biol. 59, 339-348.

66. Kahn, S.M., Klein, M.G., Jiang, W., Xing, W.Q., Xu, D.B., Perucho, M., and Weinstein, I.B. (1995).

Design of a Selectable Reporter for the Detection of Mutations in Mammalian Simple Repeat Sequences. Carcinogenesis, 16, 1223-1228.

67. Welsh J., Rampino, N., McClelland, M. and Perucho, M. (1995). Nucleic acid fingerprinting by

PCR-based methods: applications to problems in aging and mutagenesis. Mutation Research, 338, 215-219.

68. Casares, S., Ionov, Y., Ge, H-Y., Stanbridge, E. and Perucho, M. (1995) The microsatellite

mutator phenotype of colon cancer cells is often recessive. Oncogene, 11, 2303-2310. 69. Muta, H., Noguchi, M., Perucho, M., Ushio, K., Sugihara, K., Ochiai, A., Nawata, H. and Hirohashi,

S. (1996) Clinical implications of microsatellite instability in colorectal cancers. Cancer, 77, 265-270.

70. Wyborski, D., Malkhosyan, S., Moores, J., Perucho, M. and Short, J.M. (1995). Development of a

rat cell line containing stably integrated copies of a Lambda/LacI shuttle vector. Mutation Research. 334, 161-165.

71. Yasuda, J., Navarro, J.M., Malkhosyan, S., Velazquez, A, Arribas, R., Sekiya, T. and Perucho, M.

(1996). Chromosomal assignment of human DNA fingerprint sequences by simultaneous hybridization to Arbitrarily Primed PCR products from human/rodent monochromosome cell hybrids. Genomics, 34, 1-8.

72. Capella, G., Matias-Guiu, Ampudia, X., De Leiva, A., Perucho, M., Prat, J. (1996). Ras oncogene

mutations in thyroid tumors. A PCR-RFLP analysis from paraffin-enbedded tissues. Diagnostic Molecular Pathol. 5, 45-52.

73. Malkhosyan, S., McCarty, A., Sawai, H. and Perucho, M. (1996). Differences in the spectrum of

spontaneous mutations in the hprt gene between tumor cells of the microsatellite mutator phenotype. Mutation Research, 316, 249-259.

74. Achille, A., Biasi, M.O., Zamboni, G., Bogina, G., Magalini, A.R., Pederzoli, P., Perucho, M., and

Scarpa, A. (1996). Chromosome 7q allelic losses in pancreatic carcinoma. Cancer Res. 56, 3808-3813.

75. Perucho, M. (1996). Microsatellite instability: the mutator that mutates the other mutator. Nature

Medicine, 2, 630-631. 76. Yasuda, J., Kashiwabara, H., Kawakami, K, Uematsu, K., Sugano, K., Perucho. M. and Sekiya, T.

(1996). Detection of microsatellite instability in cancers by arbitrarily primed-PCR fingerprinting using the fluorescently labeled primer (FAP-PCR). Biol. Chem. 377, 563-570.

77. Perucho, M. (1996). Cancer of the microsatellite mutator phenotype. Biol. Chem. 377, 675-684. 78. Malkhosyan, S., Rampino, N., Yamamoto, H. and Perucho, M. (1996). Frameshift mutator

mutations. Nature, 382, 499-500. 79. Rampino, N., Yamamoto, H., Ionov, Y., Li, Y., Sawai, H., Reed, J. C. and Perucho, M. (1997).

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Somatic frameshift mutations in the BAX gene in colon cancers of the microsatellite mutator phenotype. Science, 275, 967-969.

80. Ricote, M., Geller, P., and Perucho, M. (1997) Frequent alterations in gene expression in colon

tumor cells of the microsatellite mutator phenotype. Mutation Res. 374, 153-167.

81. Arribas, R., Capella, G., Tortola, S., Masramon, L., Grizzle, W.E., Perucho, M. and Peinado, M.A. (1997) Assessment of genomic damage in colorectal cancer by DNA fingerprinting: prognostic applications. J. Clinical Oncol. 15, 3230-3240.

82. Yamamoto, H., Sawai, H. and Perucho, M. (1997) Frameshift somatic mutations in gastrointestinal

cancer of the microsatellite mutator phenotype. Cancer Research, 57, 4420-4426. 83. Yan, Z., Chen, M-X., Perucho, M. and Friedman, E. (1997) Oncogenic Ki-ras but not oncogenic

Ha-ras blocks integrin β1-chain maturation in colon epithelial cells. J. Biol. Chem. 272, 30928-30936.

84. Rodriguez-Bigas MA, Boland CR, Hamilton SR, Henson DE, Jass JR, Khan PM, Lynch H,

Perucho M, Smyrk T, Sobin L, Srivastava S. (1997) A National Cancer Institute Workshop on Hereditary Nonpolyposis Colorectal Cancer Syndrome: meeting highlights and Bethesda guidelines. J. Natl. Cancer Inst. 89, 1758-1762.

85. Masramon, L., Arribas, R. Tórtola, S., Perucho, M. and Peinado M.A. (1998) Moderate

amplifications of the c-myc gene correlate with molecular and clinicopathological parameters in colorectal cancer. British J. Cancer. 99, 2349-2356.

86. Yamamoto, H., Sawai, H., Weber, T.K., Rodriguez-Bigas, M.A. and Perucho, M. (1998) Somatic

frameshift mutations in DNA mismatch repair and proapoptosis genes in hereditary non polyposis colorectal cancer. Cancer Res. 58, 997-1003.

87. Malkhosyan, S., Yasuda, J., Soto, J.L., Sekiya, T., Yokota, J. and Perucho, M. (1998) Molecular

karyotype (amplotype) of metastatic colorectal cancer by unbiased arbitrarily primed PCR DNA fingerprinting. Proc. Natl. Acad. Sci. USA 95, 10170-10175.

88. Kawakami, K., Yasuda, J., Shiraishi, M., Kayama, T., Doi, K., Perucho, M. and Sekiya, T. (1998)

Detection of DNA abnormalities by arbitrarily primed PCR fingerprinting: Allelic losses in chromosome 10q in lung cancers. Biochem. Biophys. Res. Comm. 251, 153-157.

89. Perucho, M. (1999) Letter to the Editor. Correspondence re: C.R. Boland et al. A National Cancer

Institute workshop on microsatellite instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 58: 5248-5257, 1998. Cancer Res. 59, 249-253.

90. Yamamoto, H., Perez-Piteira, J., Yoshida, T., Terada, M., Itoh, F., Imai, K. and Perucho, M. (1999) Gastric cancers of the microsatellite mutator phenotype display characteristic genetic and clinical features. Gastroenterology, 116, 1348-1357.

91. Plattner, R., Gupta, S., Khosravi-Far, R., Sato, K., Perucho, M., Der, C., and Stanbridge, E. (1999) Differential contribution of the ERK and JNK mitogen-activated protein kinase cascades to Ras transformation of HT1080 fibrosarcoma and DLD-1 colon carcinoma cells. Oncogene, 18, 1807-1817.

92. Krajewski, S., Krajewska, M., Turner, B.C., Pratt, C., Howard, B., Zapata, J.M., Frenkel V., Robertson, S., Ionov, Y., Yamamoto, H., Perucho, M., Takayama, S. & Reed, J. (1999). Prog-nostic significance of apoptosis regulators in breast cancer. Endocrine-Related Cancer 6, 29-40.

93. Gil, J. Yamamoto, H., Zapata, J. M., Reed, J. C. and Perucho M. (1999) Impairment of the pro-apoptotic activity of bax by missense mutations found in gastrointestinal cancers. Cancer Res. 59, 2034-2037.

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94. Schwartz, S., Yamamoto, H., Navarro, M., Maestro, M., Reventos, J. and Perucho, M. (1999) Frameshift mutations at mononucleotide repeats in caspase-5 and other target genes, in endometrial and gastrointestinal cancer of the microsatellite mutator phenotype. Cancer Res. 59, 2995-3002.

95. Perucho, M., Perez-Piteira, J., Soto, J.L., Schwartz, S., Gascon, A., & Yamamoto, H. (1999) The

discovery of the microsatellite mutator phenotype and the distinction of the mutator and suppressor pathways for colorectal cancer. Rev. Oncología, 1, 6-12.

96. Perucho, M. Nakamura, Y. & Tokino, T. (1999) Cancer Genomics and Molecular Diagnosis--The

Ninteenth International Symposium of Sapporo Cancer Seminar Foundation. Japanese J. of Cancer Research. 90, 1273-1276.

97. Anami, Y., Takeuchi, T., Mase, K., Yasuda, J., Hirohashi, S., Perucho, M. and Noguchi, M. (2000)

Amplotyping of microdissected, methanol-fixed lung carcinoma by Arbitrarily Primed Polymerase Chain Reaction. Int. J. Cancer, 89, 19-25.

98. Yamamoto, H., Gil, J., Schwartz, S and Perucho, M. (2000) Frameshift mutations in Fas, Apaf-1,

and Bcl-10 in gastrointestinal cancer of the microsatellite mutator phenotype. Cell Death & Differentiation. 7, 238-239.

99. Malkhosyan, S., Yamamoto, H., Piao, Z. and Perucho, M. (2000) Colon Cancer of the Methylator-

Mutator Phenotype: Late Onset and High Incidence in Females. Gastroenterology. 119, 598. 100. Yamada T, Kohno T, Navarro JM, Ohwada S, Perucho M, Yokota J. (2000). Frequent

chromosome 8q gains in human small cell lung carcinoma detected by arbitrarily primed-PCR genomic fingerprinting. Cancer Genet Cytogenet. 120, 11-7.

101. Perucho, M. Genetic and epigenetic modification of MLH1. American J. Pathol. 157, 1052. 102. Ionov, Y., Yamamoto, H. Krajewski, S. Reed, J. and Perucho M. (2000) Mutational inactivation of

the pro-apoptotic gene BAX confers selective advantage during tumor clonal evolution. Proc. Natl. Acad. Sci. USA 97, 10872-10877.

103. Piao, Z., Fang, W., Malkhosyan, S., Kim, H., Horii, A., Perucho, M. and Huang, S. (2000) Frequent

frameshift mutations of RIZ in sporadic gastrointestinal and endometrial carcinomas with microsatellite instability. Cancer Res. 60, 4701-4704.

105. Schwartz, S., Perucho, M. (2000). Somatic mutations in mitochondrial DNA do not associate with

nuclear microsatellite instability in gastrointestinal cancer. Gastroenterology, 119, 1806-1807. 106. Piao, Z, Lee, K.S., Kim. H., Perucho, M. and Malkhosyan, S. (2001). Identification of novel

deletion regions on chromosomes 2q and 6p in breast carcinomas by amplotype analysis. Genes Chromosomes and Cancer. 30, 113-122.

107. Fang. W., Piao, Z., Buyse, I., Simon, D., Sheu, J-C., Perucho, M. and Huang, S. (2001).

Preferential loss of a polymorphic RIZ allele in human hepatocellular carcinoma. British J. Cancer, 84, 743-747.

108. Odero, M.D., Soto, J.L., Matutes, E., Martín J.I., Zudaire, I., Rao, P. H, Cigudosa J.C. Ardanaz,

M.T, Chaganti, R.S.K., Perucho, M., and Calasanz M.J. (2001) Comparative Genomic Hybridization and Amplotyping By Arbitrarily Primed PCR in Stage A B-CLL. Cancer Genetics and Cytogenetics. 130, 8-13.

109. Yamamoto, H., Yamashita, K. and Perucho, M. (2001) Somatic Mutation of the β2-microglobulin Gene Associates with Unfavorable Prognosis in Gastrointestinal Cancer of the Microsatellite Mutator Phenotype. Gastroenterology. 120, 1565-1567.

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110. Yamamoto H, Itoh F, Nakamura H, Fukushima H, Sasaki S, Perucho M, and Imai K. (2001) Genetic and clinical features of human pancreatic ductal adenocarcinomas with widespread microsatellite instability. Cancer Res. 61, 3139-3144.

111. Ohmiya, N., Matsumoto, S., Yamamoto, H., Baranovskaya S., Malkhosyan, S. and Perucho, M. (2001) Germline and somatic mutations in hMSH6 and hMSH3 in gastrointestinal cancers of the microsatellite mutator phenotype. Gene. 272, 301-313.

112. Yamamoto, F., Yamamoto, M., Soto, J.L., Kojima, E., Wang. E., Perucho, M., Sekiya, T., and Yamanaka, H. (2001) NotI-MseI methylation sensitive amplified fragment length polymorphism for DNA methylation analysis of human cancers. Electrophoresis. 22, 1946-1956.

113. Baranovskaya, S., Soto, J. L., Perucho. M. and Malkhosyan, S. R. (2001). Functional Significance of Concomitant Inactivation of hMLH1 and hMSH6 in Tumor Cells of the Microsatellite Mutator Phenotype. Proc. Natl. Acad. Sci. USA 98, 15107-15112.

114. Suzuki, K., Dai, T., Suzuki, I., Dai, Y., Yamashita, K., and Perucho, M. (2002) Low Mutation Incidence in Polymorphic Noncoding Short Mononucleotide Repeats in Gastrointestinal Cancer of the Microsatellite Mutator Phenotype Pathway. Cancer Res. 62, 1961-1965.

115. Yamamoto, H., Imai, K. and Perucho, M. (2002). Gastrointestinal cancer of the microsatellite mutator phenotype pathway. J. Gastroenterology. 37, 153-163.

116. Yamamoto H, Imsumran A, Taniguchi H, Min Y, Horiuchi S, Yoshida M, Iku S, Fukushima H, Sasaki S, Itoh F, Perucho M, Imai K. (2002) Microsatellite instability and gastrointestinal cancer. Gastrointest Function, 20: 51-57.

117. Perucho, M. Tumors with microsatellite instability: many mutations, targets and paradoxes Oncogene (2003) 22, 2223-2225.

118. Suzuki, K., Ohnami, S., Tanabe, C., Sasaki, H., Yasuda, J., Katai, H., Yoshimura, K., Terada, M., Perucho, M., and Yoshida, T. (2003) The genomic damage estimated by arbitrarily primed PCR DNA fingerprinting is useful for the prognosis of gastric cancer. Gastroenterology 125, 1330-1340.

119. Yamashita, K., Dai, T., Dai, Y., Yamamoto, F., and Perucho, M. (2003) Genetics supersedes epigenetics in colon cancer phenotype. Cancer Cell 4, 121-131.

120. Ionov Y., Nowak N., Perucho M., Markowitz S., Cowell JK. (2004) Manipulation of nonsense mediated decay identifies gene mutations in colon cancer cells with microsatellite instability. Oncogene. 23, 639-645.

121. Li, H.-R., Shagisultanova, E.I., Yamashita, K, Piao, Z., Perucho, M., and Malkhosyan, S.R. (2004) Hypersensitivity of tumor cell lines with microsatellite instability to DNA double strand break producing chemotherapeutic agent bleomycin. Cancer Research, 64, 4760-4767.

122. Yi ES, Strong CR, Piao Z, Perucho M, Weidner N. (2005) Epithelioid gastrointestinal stromal tumor with PDGFRA activating mutation and immunoreactivity. Appl. Immunohistochem Mol Morphol. 13, 157-61.

123. Krajewska, M., Kim, H., Kim, C., Kang, H., Welsh, K., Matsuzawa, S., Tsukamoto, M., Thomas, R.G., Assa-Munt, N., Piao, Z., Suzuki, K., Perucho, M., Krajewski, S. and Reed, J.C. (2005). Analysis of Apoptosis Protein Expression in Early-Stage Colorectal Cancer Suggests Opportunities for New Prognostic Biomarkers. Clinical Cancer Res. 11, 5451-5461.

124. Rodriguez G, Bilbao C, Ramirez R, Falcon O, Leon L, Chirino R, Falcon Jr R, Diaz BP, Rivero JF, Perucho M, Diaz-Chico BN, and Diaz-Chico JC. Alleles with short CAG and GGN repeats in the androgen receptor gene are associated with benign endometrial cancer. International Journal of Cancer. Int J Cancer 118, 1420-1425. 2006.

125. Suzuki, K., Suzuki I., Leodolter, A., Alonso, S., Horiuchi, S., Yamashita, K., and Perucho, M. (2006) Global DNA demethylation in gastrointestinal cancer is age-dependent and precedes genomic damage. Cancer Cell, 9, 199-207.

126. Bilbao C, Rodriguez G, Ramirez R, Falcon O, Leon L, Chirino R, Rivero JF, Falcon Jr R, Diaz-Chico BN, Diaz-Chico JC, and Perucho M. (2006) The relationship between microsatellite

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instability and PTEN gene mutations in endometrial cancer. International Journal of Cancer. 119, 563-70.

127. Schwartz S., Jr, Menoyo, A, and Perucho, M. (2006) Mutational Dynamics in Human Tumors Confirm the Neutral Intrinsec Instability of the Mitochondrial D-Loop Poly-Cytidine Repeat Genes Chromosomes & Cancer, 45, 770-80..

128. Davalos V, Dopeso H, Velho S, Ferreira AM, Cirnes L, Diaz-Chico N, Bilbao C, Ramirez R, Rodriguez G, Falcon O, Leon L, Niessen R, Keller G, Dallenbach-Hellweg G, Espin E, Armengol M, Perucho M, Imai K, Yamamoto H, Gebert JF, Diaz-Chico JC, Hofstra RM, Woerner SM, Seruca R, Schwartz Jr. S, Arango D. (2007) High EPHB2 mutation rate in gastric but not endometrial tumors with microsatellite instability. Oncogene, 26, 308-311.

129. Perucho M, Suzuki K, (2007) New insights into a controversial topic: The methylation-cancer connection, Gastroenterology, 132, 2070-2071.

130. Zhou, W., Alonso, S., Takai, D., Yamamoto, F., Perucho, M. and Huang, S. Requirement of RIZ1 for Cancer Prevention by Methyl-Balanced Diet (2008). PLos One, 3, 3390-3396.

131. Baranovskaya S, Martin Y, Alonso S, Pisarchuk KL, Falchetti M, Dai Y, Khaldoyanidi S, Krajewski S, Novikova I, Sidorenko YS, Perucho M, and Malkhosyan SR. (2009) Down-regulation of EGFR by selective expansion of a 5’ end regulatory dinucleotide repeat in colon cancer with microsatellite instability, Clin Cancer Res 15, 4531-4537.

132. Bilbao, C. Lara, Ramirez, R. Henriquez-Hernandez, LA., Rodriguez, G., Falcon, O., Leon, L Perucho, M., Diaz-Chico, BN and Diaz-Chico, JC.. (2010). Microsatellite instability predicts clinical outcome in radiation-treated endometrioid endometrial cancer. Int J Radiat Oncol Biol Phys 76, 9-13.

133. Bilbao C, Ramírez R, Rodríguez G, Falcón O, León L, Díaz-Chico N, Perucho M, Díaz-Chico JC. (2010) Double strand break repair components are frequent targets of microsatellite instability in endometrial cancer. Eur J Cancer, 46(15):2821-7.

134. Samuelsson, J., Alonso, S., Yamamoto, F., and Perucho, M. Fingerprinting Techniques for Genetic and Epigenetic Alterations in Colorectal Cancer. Mutation Res, 693, 61-76.

135. Samuelsson J, Alonso S, Ruiz-Larroya T, Cheung TH, Wong YF, Perucho M. (2011) Frequent somatic demethylation of RAPGEF1/C3G intronic sequences in gastrointestinal and gynecological cancer. Int. J. Oncol. 38(6):1575-7.

136. Koizumi, K., Alonso., Miyaki, Y., Okada, S., Ogura, H., Shiiya, N., Konishi, F., Taya, T., Perucho, M. and Suzuki, K. (2012). Array-based identification of common DNA methylation alterations in ulcerative colitis. Int. J. Oncol. Apr;40(4):983-94. Epub 2011 Dec 6 2011.

137. Kamiyama, H., Suzuki, K., Maeda, T., Koizumi, K., Miyaki, Y., Okada, S., Kawamura, Y.J., Samuelsson, J.K., Alonso, S., Konishi, F. and Perucho, M. (2012) DNA demethylation in normal colon tissue predicts predisposition to multiple cancers. Oncogene, 31 (48) 5029-5037.

Curriculum Vitae

Joaquín V. Arribas López (Fecha Nacimiento: 12/12/1964)

DIRECCIÓN

Preclinical Research Program

Vall d’Hebron Institut d'Oncologia (VHIO)

Pssg. Vall d’Hebron 119-129

Barcelona 08035

Tel.: +34 93 274 6026

Fax: +34 93 489 3884

e-mail: jarribas@vhio.net

EDUCACIÓN

1987 Licenciatura en Biología (Bioquímica y Biología Molecular). Universidad Autónoma de Madrid

1992 PhD Docotorado en Ciencias (Biologia). Universidad Autónoma de Madrid

POSICIÓN ACTUAL

2007- actualidad. ICREA Research Professor. Institució Catalana de Recerca i Estudis Avançats (ICREA).

(http://www.icrea.es/).

2011- actualidad Director Programa de Investigación Preclinica, Vall d’Hebron Institut d’Oncologia (VHIO)

2009- actualidad Profesor Asociado , Departmento de Bioquimica y Biologia Molecular, Universitat Autónoma de

Barcelona (UAB).

EXPERIENCIA PROFESIONAL Y ACADEMICA 1988-1992 Predoctoral Fellow, Ministerio de Educación y Ciencia. Facultad de Medicina, UAM

Jun-Oct 1990 Predoctoral Fellow, National Cancer Institute. Frederick Cancer Research Facility

1993-1997 Postdoctoral fellow. Ministerio de Educación y Ciencia. Memorial Sloan-Kettering Cancer Center.

1997-2006 Faculty, Institut Catalá de la Salut (ICS). Hospital Universitario Vall d’Hebron

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Publicaciones

García-Parra, J., Arpí, O., Morancho, B., Dalmases, A., Menendez, S., Zazo, S., Chamizo

, C., Eroles, P.,

Servitja, S., Tusquets, I., Yelamos, J., Lluch, A., Arribas, J., Rojo, F., Rovira, A. and Albanell, J. Poly

(ADP-ribose) polymerase inhibition enhances trastuzumab antitumor activity in HER2 overexpressing

breast cancer (2012) Submitted.

Serra, V., Eichhorn, P. J. A., Celina García-García, C., Ibrahim, Y. I., Prudkin, P., Sánchez, G., Rodríguez,

O., Antón, P., Parra, J. Ll., Marlow, S., Scaltriti, M., Aleix Prat4, Arribas, J., Hahn, W. C., Kim, S. Y. and

Baselga, J. (2013) RSK3/4 mediate resistance to PI3K pathway inhibitors in breast cancer. J Clin Invest, in

press.

Pedersen, K., Canals, F., Tabernero, J. and Arribas, J. (2012) PELO negatively regulates HER-receptor

signalling and metastasis (2013) Oncogene 2012, Feb 25 doi: 10.1038/onc.2013.35. [Epub ahead of print].

(http://www.nature.com/onc/journal/vaop/ncurrent/full/onc201335a.html).

Angelini, P. D., Zacarias-Fluck, M. F., Parra-Palau, J. Ll., Guiu, M., Pedersen, K., Bernadó Morales, C.,

Luque-García, A., Peiró Novalpotro, N., Giralt, J., Canals, F., Villanueva, J., Gomis, R. R., Baselga, J. and

Arribas, J. (2013) Constitutive HER2 signaling promotes breast cancer metastasis through cellular

senescence. Cancer Res, 73, 450-458. (http://cancerres.aacrjournals.org/content/73/1/450.abstract)

Morancho, B., Parra-Palau, J. Ll., Ibrahim, Y. H., Bernadó Morales, C., Bech-Serra, J. J., Pandiella, A.,

Canals, F., Baselga, J. and Arribas, J. (2013) A dominant negative N-terminal fragment of HER2

frequently expressed in breast cancers. Oncogene 32, 1452-1459.

(http://www.nature.com/onc/journal/v32/n11/full/onc2012152a.html) Epub 2012 May 28.

Koziol, A., Gonzalo, P., Mota, A., Pollán, A., Lorenzo, C., Colomé, N., Montaner, D., Dopazo, J., Arribas,

J., Canals, F., Arroyo, A. G. (2012) The protease MT1-MMP drives a combinatorial proteolytic program in

activated endothelial cells. FASEB J 26, 4481-4494. (http://www.fasebj.org/content/26/11/4481.abstract)

Esteve, P., Sandonìs, A., Cardozo, M., Malapeira, J., Ibañez,

C., Crespo, I., Gonzalez-Garcia,

S., Marcos,

S., Torribio, M. L., Arribas, J., Shimono, A., Guerrero, I. and Bovolenta, P. (2011) Secreted Frizzled-

Related Proteins act as negative modulators of ADAM10 metalloproteinase activity during retinal

neurogenesis. Nat Neurosci 14, 562-569. http://www.nature.com/neuro/journal/v14/n5/full/nn.2794.html.

Article recommended by Faculty of 1000 (http://f1000.com/11005956#evaluations)

Arribas, J., Baselga, J., Pedersen, K. and Parra-Palau, J. Ll. (2011) p95HER2 and breast cancer. Cancer

Res 71, 1515-1519. http://cancerres.aacrjournals.org/content/71/5/1515.abstract

Serra, V., Scaltriti, M., Prudkin, L., Eichhorn, P., Ibrahim, Y. H., Chandarlapaty, S., Markman, B.,

Rodriguez, O., Guzman, M., Rodriguez, S., Gili, M., Russillo, M., Parra, J. Ll., Singh, S., Arribas, J.,

Rosen, N., and Baselga, J. (2011) PI3K inhibition results in enhanced HER signaling and acquired ERK

dependency in HER2 overexpressing breast cancer. Oncogene 30, 2547-2557.

3

Malapeira, J., Esselens, C., Bech-Serra, J. J. Canals, F., Arribas J. (2011) ADAM17 (TACE) regulates

TGFbeta signaling through the cleavage of vasorin. Oncogene 30, 1912-1922.

http://www.nature.com/onc/journal/v30/n16/full/onc2010565a.html

Parra-Palau, J. Ll., Pedersen, K., Peg, V., Scaltriti, M., Angelini, P. D., Escorihuela, M., Mancilla, S.,

Sánchez-Pla, A., Ramón y Cajal, S., Baselga, J., Arribas, J. (2010) A major role of p95/611-CTF, a

carboxy-terminal fragment of HER2, in the downmodulation of the ER in HER2-positive breast cancers.

Can Res 70, 8537-8546. http://cancerres.aacrjournals.org/content/70/21/8537.

Arribas, J., Parra-Palau, J. L., Pedersen, K. (2010) HER2 fragmentation and breast cancer stratification.

Clin Can Res 16, 4071-4073. http://clincancerres.aacrjournals.org/content/16/16/4071.

Scaltriti, M., Chandarlapaty, S., Prudkin, L., Aura, C., Jimenez, J., Angelini, P. D., Sánchez, G., Guzman,

M., Parra, J. L., Ellis, C., Gagnon, R., Koehler, M., Gomez, H., Geyer, C., Cameron, D., Arribas, J.,

Rosen, N. and Baselga J. (2010) Clinical Benefit of lapatinib-based therapy in patients with human

epidermal growth factor receptor-2-positive breast tumors coexpressing the truncated p95HER2 receptor.

Clin Cancer Res 16, 2688-2695. http://clincancerres.aacrjournals.org/content/16/9/2688.

Esselens, C., Malapeira, J., Colome, N., Casal, C., Rodriguez-Manzaneque, J. C., Canals, F. and Arribas,

J. (2010) The cleavage of semaphorin 3C induced by ADAMTS1 promotes cell migration. J Biol Chem 285,

2463-2473. http://www.jbc.org/content/285/4/2463.abstract.

Chandarlapaty, S., Scaltriti, M., Angelini, P., Ye, Q., Guzman, M., Hudis, C. A., Norton, L., Solit, D. B.,

Arribas, J., Baselga, J. and Rosen, N. (2010) Inhibitors of HSP90 block p95-HER2 signaling in

Trastuzumab-resistant tumors and suppress their growth. Oncogene 29, 325-334.

http://www.nature.com/onc/journal/v29/n3/abs/onc2009337a.html. “Featured Original Article” of the issue

Pedersen, K., Angelini, P.-D., Laos, L., Bach-Faig, A., Cunningham, M.-P., Ferrer-Ramón, C., Luque-

García, A., García-Castillo, J., Parra-Palau, J.-Ll., Scaltriti, M., Ramón y Cajal, S., Baselga J. and Arribas,

J. (2009) A Naturally Occurring HER2 Carboxy-Terminal Fragment Promotes Mammary Tumor Growth

and Metastasis. Mol Cell Biol 29, 3319-3331. http://mcb.asm.org/cgi/content/full/29/12/3319. Article

Recommended by Faculty of 1000 (http://f1000biology.com/article/id/1163335/evaluation)

García-Castillo, J., Pedersen, K., Angelini, P. D., Bech-Serra, J. J., Colome, N., Cunningham, M. P., Parra

Palau, J. Ll., Canals, F., Baselga, J. and Arribas, J. (2009) HER2 carboxy terminal fragments regulate cell

migration and cortactin phosphorylation. J Biol Chem 284, 25302-25313.

http://www.jbc.org/cgi/reprint/M109.001982

Arribas, J. and Esselens, C. (2009) ADAM17 as a Therapeutic Target in Multiple Diseases. Curr Pharm

Des 15, 2319-2335. http://www.bentham.org/cpd/contabs/cpd15-20

Serra, V., Markman, B., Scaltriti, M., Eichhorn, P. J., Valero, V., Guzman, M., Botero, M. L., Llonch, E.,

Atzori, F., Di Cosimo, S., Maira, M., Garcia-Echeverria, C., Parra, J. Ll., Arribas, J. and Baselga, J. (2008)

NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells

with activating PI3K mutations. Cancer Res. 68:8022-8030.

(http://cancerres.aacrjournals.org/cgi/content/full/68/19/8022)

Vilar, E., Scaltriti, M., Balmana, J., Saura, C., Guzman, M., Arribas, J., Baselga, J. and Tabernero J.

(2008) Microsatellite instability due to hMLH1 deficiency is associated with increased cytotoxicity to

4

irinotecan in human colorectal cancer cell lines. Br J Cancer. 99,1607-1612.

(http://www.nature.com/bjc/journal/v99/n10/abs/6604691a.html)

Scaltriti, M., Verma, C., Guzman, M., Jimenez, J., Parra, J. Ll., Pedersen, K., Smith, D. J., Landolfi, S.,

Ramon y Cajal, S., Arribas, J. and Baselga, J. (2009). Lapatinib, a HER2 tyrosine kinase inhibitor, induces

stabilization and accumulation of HER2 and potentiates trastuzumab-dependent cell cytotoxicity.

Oncogene 86, 803-814. (http://www.nature.com/onc/journal/vaop/ncurrent/abs/onc2008432a.html

Scaltriti, M., Rojo , F., Ocaña, A., Anido

, J., Guzman, M., Cortes, J., Di Cosimo, S., Matias-Guiu, X.,

Ramon y Cajal, S., Arribas, J., & Baselga, J. (2007) p95HER2, a truncated form of the HER2 receptor,

and response to anti-HER2 therapies in breast cancer. J Natl Cancer Inst. 99, 628-638.

(http://jnci.oxfordjournals.org/cgi/content/full/99/8/628)

Esselens, C. W., Malapeira, J., Colome, N., Moss, M., Canals, F. and Arribas, J. (2008) Metastasis-

associated C4.4A, a GPI-anchored protein cleaved by ADAM10 and ADAM17. Biol Chem. 389, 1075-1084.

(http://www.ncbi.nlm.nih.gov/pubmed/18979631?dopt=Citation)

Santiago-Josefat, B., Esselens, C., Bech-Serra, J. J. and Arribas, J. (2007) Post-transcriptional

upregulation of ADAM17 upon EGFR activation and in breast tumors. J Biol Chem 282, 8325-8331.

(http://www.jbc.org/cgi/content/full/282/11/8325) Article Recommended by Faculty of 1000

(http://www.f1000biology.com/article/id/1071114/evaluation)

Arribas, J., Bech Serra, J. J. and Santiago Josefat, B. (2006) ADAMs, cell migration and cancer Cancer

Met Rev. 25, 57-68. (http://www.springerlink.com/content/r4678440p1163673)

Bech Serra, J. J., Santiago Josefat, B., Esselens C., Saftig, P., Baselga, J. Arribas, J.* and Canals, F.

(2006) Proteomic Identification of Desmoglein-2 and ALCAM as substrates of ADAM17 and ADAM10 by

Difference Gel Electrophoresis. Mol Cell Biol 26, 5086-5095 (* Corresponding autor).

(http://mcb.asm.org/cgi/content/full/26/13/5086)

Zatovicova, M., Sedlakova, O., Svastova, E., Ohradanova, A., Ciampor, , F., Arribas, J., Pastorek, J. and

Pastorekova, S. (2005) Ectodomain shedding of the hypoxia-induced carbonic anhydrase IX is a

metalloprotease-dependent process regulated by TACE/ADAM17 B J Cancer 93, 1267-1276.3

Anido, J., Scaltriti, M., Bech Serra, J. J., Federico Rojo, F. Baselga, J. and Arribas, J. (2006) Biosynthesis

of tumorigenic HER2 C-terminal fragments by alternative initiation of translation. EMBO J. 25, 3234-3244.

(http://www.nature.com/emboj/journal/v25/n13/abs/7601191a.html)

Arribas J. and Baselga, J. (2005) Who will benefit from anti-EGFR therapy (2005) Lancet Oncol 6, 257-

258. (http://www.sciencedirect.com)

Arribas J. (2005) Matrix metalloproteases and tumor invasion. New Eng J Med. 352, 2020-2021.

(http://content.nejm.org/cgi/content/extract/352/19/2020)

Martínez-Arca, S., Hurtando-Küttner, M., Borroto, A., and Arribas, J. (2005) Recycling of cell surface

proTGF-alpha regulates EGFR activation. J Biol Chem 280, 36970-3697.

(http://www.jbc.org/cgi/content/full/280/44/36970)

Arribas, J. and Ruiz-Paz, S. (2005) Regulation of ectodomain shedding. The ADAM Family of

Metalloproteases. Edited by Hopper and Lendeckel. Kluwer plenum

5

1997 Baselga, J. and Arribas, J. (2004) Treating cancer’s kinase “addiciton”. Nat Med 10, 786-787.

(http://www.nature.com/cgi-taf/DynaPage.taf?file=/nm/journal/v10/n8/abs/nm0804-

786.html&dynoptions=doi1092047177).

Juanes, P. P., Ferreira, L., Montero, J. C., Arribas, J. and Pandiella. A. (2005) N-terminal cleavage of

proTGF occurs at the cell surface by a TACE-independent activity. Biochem. J 389, 161-172.

(http://www.biochemj.org/bj/389/0161/bj3890161.htm)

Helmke, B. M., Polychronidis, M., Benner, A., Thome, M., Arribas, J. and Deichmann, M. (2004)

“Melanoma metastasis is associated with enhanced expression of the syntenin gene” Oncol Rep 12, 221-

228. (http://147.52.72.117/OR/2004/volume12/number2/221.pdf)

Matar, P., Rojo, F., Cassia, R., Moreno-Bueno, G., Di Cosimo, S., Guzman, M., Rodriguez, S., Arribas, J.,

Palacios, J., Baselga, J. (2004) Combined epidermal growth factor receptor (EGFR) targeting with the

tyrosine kinase inhibitor gefitinib (ZD1839) and the monoclonal antibody cetuximab (IMC-C225):

Superiority over single-agent receptor targeting. Clin Cancer Res 9, 1274-1283

(http://clincancerres.aacrjournals.org/cgi/content/full/9/4/127)

Villanueva de la Torre, T., Bech-Serra, J. J., Ruiz-Paz, S., Baselga, J., Arribas, J. (2004) Inactivating

mutations block the Tumor Necrosis Factor-Alpha Converting Enzyme in the early secretory pathway

Biochem Biophys Res Commun 314, 1028-1035. (http://www.sciencedirect.com)

Velasco-Loyden, G., Arribas, J., López-Casillas, F. (2004) The shedding of Betaglycan is regulated by

pervanadate and inhibited by TIMP-2. J Biol Chem 279, 7721 - 773

(http://www.jbc.org/cgi/content/full/279/9/7721)

Borroto, A., Ruíz-Paz, S., Borrell-Pagès, M., Villanueva de la Torre, T., Merlos-Suárez, A., Blobel, C. P.,

Baselga, J., and Arribas, J. (2003). A specific mechanism mediates the intracellular trafficking and

activation of TACE. J Biol Chem. 278, 25932-25939. (http://www.jbc.org/cgi/reprint/M301673200v1)

Anido, J., Matar, P., Albanell, J., Guzman, M., Rojo, F., Arribas, J., Averbuch, S. & Baselga, J. (2003).

ZD1839 (Gefitnib), a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, induces

the formation of inactive EGFR/HER2 and EGFR/HER3 heterodimers and prevents heregulin signaling in

HER2 overexpressing breast cancer cells. Clin Cancer Res 9, 1274-83.

(http://clincancerres.aacrjournals.org/cgi/content/full/9/4/1274)

Borrell-Pagès, M., Rojo, F., Albanell, J., Baselga, J., and Arribas, J. (2003) TACE is required for the

activation of the EGFR by TGF-alpha in tumors, EMBO J 22, 1114-1124.

(http://emboj.oupjournals.org/cgi/content/full/22/5/1114) Article classified as “Must Read” by Faculty of

1000 (http://www.f1000biology.com/article/id/1012467/evaluation)

Arribas, J. & Merlos-Suarez, A. (2003). Shedding of plasma membrane proteins. Curr Top Dev Biol

54,125-144.

Arribas, J. & Borroto, A. (2002). Protein Ectodomain Shedding. Chem Rev 102, 4627-4638.

(http://pubs3.acs.org/acs/journals/doilookup?in_doi=10.1021/cr010202t)

Mayo, I., Arribas, J., Villoslada, P., Alvarez DoForno, R., Rodriguez-Vilarino, S., Montalban, X., de

Sagarra, M. R., and Castano, J. G. (2002). The proteasome is a major autoantigen in multiple sclerosis.

Brain 125, 2658-2667. (http://brain.oupjournals.org/cgi/content/abstract/125/12/2658)

6

Baselga, J., Albanell, J., Molina, M., and Arribas, J. (2001). Mechanism of action of trastuzumab and

scientific update. Semin Oncol 28, 4-11.

Merlos-Suarez, A., Ruiz-Paz, S., Baselga, J., and Arribas, J. (2001). Metalloprotease-dependent

Protransforming Growth Factor-alpha Ectodomain Shedding in the Absence of Tumor Necrosis Factor-

alpha -converting Enzyme. J Biol Chem. 276, 48510-48517.

(http://www.jbc.org/cgi/content/full/276/51/48510)

Molina, M. A., Codony-Servat, J., Albanell, J., Rojo, F., Arribas, J., and Baselga, J. (2001). Trastuzumab

(Herceptin), a Humanized Anti-HER2 Receptor Monoclonal Antibody, Inhibits Basal and Activated HER2

Ectodomain Cleavage in Breast Cancer Cells. Cancer Res 61, 4744-4749.

(http://cancerres.aacrjournals.org/cgi/content/full/61/12/4744

Velasco, G., Cal, S., Merlos-Suarez, A., Ferrando, A. A., Alvarez, S., Nakano, A., Arribas, J., and Lopez-

Otin, C. (2000). Human MT6-Matrix Metalloproteinase: Identification, Progelatinase A Activation, and

Expression in Brain Tumors. Cancer Res 60, 877-882.

(http://cancerres.aacrjournals.org/cgi/content/full/60/4/877)

Rodriguez-Vilarino, S., Arribas, J., Arizti, P., and Castano, J. G. (2000). Proteolytic Processing and

Assembly of the C5 Subunit into the Proteasome Complex. J Biol Chem 275, 6592-6599.

(http://www.jbc.org/cgi/content/full/275/9/6592)

Jesús M. Ureña, J. M., and Arribas, J. (2000). El transporte intracelular de proteínas. El caso del TGF-

alfa. Ciencia al Dia Internacional 3, 1-14.

(http://www.ciencia.cl/CienciaAlDia/volumen3/numero1/articulos/articulo2.html)

Borrell-Pages, M., Fernandez-Larrea, J., Borroto, A., Rojo, F., Baselga, J., and Arribas, J. (2000). The

Carboxy-terminal Cysteine of the Tetraspanin L6 Antigen Is Required for Its Interaction with SITAC, a

Novel PDZ Protein. Mol Biol Cell 11, 4217-4225. (http://www.molbiolcell.org/cgi/content/full/11/12/4217)

Roghani, M., Becherer, J. D., Moss, M. L., Atherton, R. E., Erdjument-Bromage, H., Arribas, J., Blackburn,

R. K., Weskamp, G., Tempst, P., and Blobel, C. P. (1999). Metalloprotease-Disintegrin MDC9: Intracellular

Maturation and Catalytic Activity. J Biol Chem. 274, 3531-3540.

(http://www.jbc.org/cgi/content/full/274/6/3531)

Urena, J., Merlos-Suarez, A., Baselga, J., and Arribas, J. (1999). The cytoplasmic carboxy-terminal amino

acid determines the subcellular localization of proTGF-(alpha) and membrane type matrix metalloprotease

(MT1-MMP). J Cell Sci 112, 773-784. (http://www.biologist.com/JCS/112/06/jcs98333.html)

Fernández-Larrea, J., Merlos-Suárez, A., Ureña, J. M., Baselga, J., and Arribas, J. (1999). A Role for a

PDZ Protein in the Early Secretory Pathway for the Targeting of proTGF-a to the Cell Surface. Mol Cell 3,

423-433. (http://www.molecule.org/cgi/content/abstract/3/4/423)

Merlos-Suarez, A., and Arribas, J. (1999). Mechanisms controlling the shedding of transmembrane

molecules. Biochem Soc Trans 27, 243-246.

Codony-Servat, J., Albanell, J., Lopez-Talavera, J. C., Arribas, J., and Baselga, J. (1999). Cleavage of the

HER2 Ectodomain Is a Pervanadate-activable Process That Is Inhibited by the Tissue Inhibitor of

Metalloproteases-1 in Breast Cancer Cells. Cancer Res 59, 1196-1201.

(http://cancerres.aacrjournals.org/cgi/content/full/59/6/1196)

7

Merlos-Suarez, A., Fernandez-Larrea, J., Reddy, P., Baselga, J., and Arribas, J. (1998). Pro-Tumor

Necrosis Factor-alpha Processing Activity Is Tightly Controlled by a Component That Does Not Affect

Notch Processing. J Biol Chem. 273, 24955-24962. (http://www.jbc.org/cgi/content/full/273/38/24955)

Arribas, J., Lopez-Casillas, F., and Massague, J. (1997). Role of the Juxtamembrane Domains of the

Transforming Growth Factor-alpha Precursor and the beta -Amyloid Precursor Protein in Regulated

Ectodomain Shedding. J Biol Chem. 272, 17160-17165. (http://www.jbc.org/cgi/content/full/272/27/17160)

Arribas, J., Coodly, L., Vollmer, P., Kishimoto, T. K., Rose-John, S., and Massagué, J. (1996). Diverse

Cell Surface Protein Ectodomains Are Shed by a System Sensitive to Metalloprotease Inhibitors. J Biol

Chem. 271, 11376-11382. (http://www.jbc.org/cgi/content/full/271/19/11376)

Castano, J. G., Mahillo, E., Arizti, P., and Arribas, J. (1996). Phosphorylation of C8 and C9 subunits of the

multicatalytic proteinase by casein kinase II and identification of the C8 phosphorylation sites by direct

mutagenesis. Biochemistry 35, 3782-3789.

Arribas, J., and Massague, J. (1995). Transforming growth factor-alpha and beta-amyloid precursor

protein share a secretory mechanism. J Cell Biol. 128, 433-441. (http://www.jcb.org/cgi/reprint/128/3/433)

Arribas, J., Arizti, P., and Castano, J. (1994). Antibodies against the C2 COOH-terminal region

discriminate the active and latent forms of the multicatalytic proteinase complex. J Biol Chem. 269, 12858-

12864.

Ruiz de Mena, I., Mahillo, E., Arribas, J., and Castano, J. G. (1993). Kinetic mechanism of activation by

cardiolipin (diphosphatidylglycerol) of the rat liver multicatalytic proteinase. Biochem J 296, 93-97.

Arribas, J., and Castano, J. (1993). A comparative study of the chymotrypsin-like activity of the rat liver

multicatalytic proteinase and the ClpP from Escherichia coli. J Biol Chem. 268, 21165-21171.

Arizti, P., Arribas, J., and Castano, J. G. (1993). Modulation of the multicatalytic proteinase complex by

lipids, interconversion and proteolytic processing. Enzyme Protein 47, 285-295.

Arribas, J., Luz Rodriguez, M., Alvarez-Do Forno, R., and Castano, J. (1991). Autoantibodies against the

multicatalytic proteinase in patients with systemic lupus erythematosus. J Exp. Med. 173, 423-427.

Arribas, J., and Castano, J. (1990). Kinetic studies of the differential effect of detergents on the peptidase

activities of the multicatalytic proteinase from rat liver. J Biol Chem. 265, 13969-13973.

Patentes

Patent 1

8

Tittle: METHOD FOR DIAGNOSING CANCERS EXPRESSING THE HER2 RECEPTOR OR ITS TRUNCATED VARIANTS

Inventors (by order of signature): Joaquim Arribas; Kim Pedersen; Davide Angellini; Josep Lluis Parra; Sirle Laos; Josep Baselga

Request Nr: P200801652

Priority Country: Spain

Priority Date: 02/06/2008

Entity: Institut de Recerca Hospital Universitari Vall d’Hebron; Fundació Privada Institut d’Investigació Òncologia de Vall d’Hebron; Institució Catalana de Recerca i Estudis Avançats

Extended Countries: Australia, Brasil, Canada, Suïssa, China, Eurasia, Europa, Hong Kong, Israel, India, Japó, Mèxic, Singapur, Estats Units d’Amèrica, Uruguai, Veneçuela, Sud-àfrica.

Companies exploiting it: GlaxoSmithKline

Patent 2

Tittle: ANTIBODIES AGAINST HER2 TRUNCATED VARIANT CTF-611

Inventors (by order of signature): Joaquim Arribas; Kim Pedersen; Davide Angellini; Josep Lluis Parra; Josep Baselga

Request Nr: EP 09380183,5

Priority Country: Europe

Priority Date: 07/12/2009

Entity: Fundació Privada Institució Catalana de Recerca i Estudis Avançats; Fundació Privada Institut d’Investigació Oncològica de Vall d’Hebron

Extended Countries: Europa, Estats Units d’Amèrica, Japó

Companies exploiting it: GlaxoSmithKline

Patente 3

Tittle: METODO DE DIAGNOSTICO DE LA ENFERMEDAD DE ALZHEIMER QUE EMPLEA SFRP1 COMO BIOMARCADOR

Inventors (by order of signature): Paola Bovolenta, Pilar Esteve, Africa Sandonis, Inmaculada Crespo, Mª Isabel Guerrero, Carmen Ibáñez, Jordi Malapeira, Joaquin Arribas, Shimono Akihiko

Request Nr: P201130560

Priority Country: Spain

Priority Date: 08/04/2011

Entity: Consejo Superior de Investigaciones Científicas; Vall d’Hebron Institut de Recerca; Vall d’Hebron Institute of Oncology; Institució Catalana de Recerca i Estudis Avançats; National University of Singapore

Extended Countries: None

Companies exploiting it: None

Patente 4

Tittle: MT1-MMP SUBSTRATES AS BIOMARKERS OF INFLAMMATORY ANGIOGENESIS

Inventors (by order of signature): Alicia Gárcia, Agniezka Koziol, Francesc Canals, Nuria Colome, Joaquín Arribas

Request Nr: EP 11382255,5

Priority Country: Europe

Priority Date: 26/07/2011

Entity: Fundación Centro Nacional de Investigaciones Cardiovasculares Carlos III; Institució Catalana de Recerca i Estudis Avançats; Institut de Recerca Hospital Universitari Vall d’Hebron; Fundació Privada Institut d’Investigació Oncològica de Vall d’Hebron

Extended Countries: PCT application

Companies exploiting it: None

9

Seleccción de Conferencias (entre más de 100 comunicaciones):

Charla “Immunotherapy against breast cancer” en el Congreso “Cancer Immunotherapy” in Societat

Catalana d’Immunologia (SCI). Noviembre 2012

Participación en la tertulia sobre el cancer de mama del programa “Para todos la 2” de RTVE. Octubre

2012

Seminario “HER2 overexpression cellular senescence and metastasis in Breast Cancer. Centro de

Investigación Cooperativa (CiC) Biogune (Bilbao), Octubre 2012.

IMRA Conference (International Medical Research Association). Kobe (Japan) Junio 2012

Universidad del País Vasco XXXI Cursos del verano en San Sebastián – XXIV Cursos Europeos. Investigación e

Innovación en el ámbito Biosanitario. Participación en Mesa redonda. “Experiencia en el Vall d’Hebrón y en la

RTICC”. Julio 2012

Conferences cicle “Desafiaments del Segle XXI, IV, la veu de la Medicina, I” at Residencia d’Investigadors. May,

2012. Title: “Hacia la personalización en el cancer de mama”

Master de Oncología Molecular: Bases moleculares del cáncer. VIII edición 2012-2014. Clase impartida:

“Oncogenes que codifican factores de crecimiento y receptores tirosina-quinasa” Centro Nacional de

Investgaciones Oncológicas (CNIO) Abril 2012. (TRADUCIR!!)

Seminario en Biotech Research and Innovation Centre (BRIC), Copenhague (Dinamarca). Título charla: “HER-2

induced cellular senescence and breast cancer metastasis. Marzo 2012.

International Symposioum on Intracellular Proteosisys and Cancer (EMBO). Valencia. Title: “Cell Signaling through

protein ectodomain shedding”. November 2011

CNIO . Programa de Patología Molecular. Seminar: Title: “HER2 hyperactivation in breast cancer, from senescente

to metastasis” September 2011

Friederich Miescher Institute for Biomedical Research. Title: Series “Growth control and cancer” seminar: April,

12th 2011

IMRA Conference (International Medical Research Association). Title: “Towards personalizad cancer medicine. Breast Cancer Patients Stratification” February 17th -18th 2011 CNIO Frontiers Meeting: “Breast Cancer”. Title: “Hyperactivation of HER2 and anti-HER2 therapies” February 7th-9th 2011 Towards Personalized Cancer Medicine Conference. Title: “A major Role of 611-CTF, a Carboxy-Terminal

Fragment of HER2, in the Downmodulation of ER in HER2- Positive Breast Cancers” May, 20th 2010.

Kiel University, Medical Faculty. Title: “Specifity and Pathophysiology of Signal Transduction Pathways”

November 26th, 2009.

CNIO Seminar. Title: “The EGFR receptor pathway in breast cancer progression and treatment” Madrid, October,

1st 2009.

5th General Meeting of the International Proteolysis Society. Title: “Proteomic identification and

characterization of ADAM substrates” Patras, Greece, October, 22th 2007.

10

Gordon Research Conference on Matrix Matrix Metalloprotease. Title: “Identification and characterization of novel

ADAM and ADAMTS substrates”. Il Ciocco, Italy, June 5th 2007.

Metzincin Metalloproteases in Health and Diseases. Title: “Proteomic identification and characterization of ADAM

substrates”. Ascona, Switzerland, September 25th, 2006.

3rd

Annual Symposium on Anti-Signaling Strategies in Human Neoplasia. Title: “Characterization of a novel

product of the oncogene ErbB2”, Barcelona, September 16th, 2004 (Chairman of the session).

Gordon Research Conference on Matrix Metalloproteases. Title: "Role of TACE in EGFR-Ligand Activation and

Tumor Development", Big Sky, MT, USA, Agust 20th 2003.

Inaugural Conference, XII National Congress on Bioenergetics and Biomembranes. Title: "Biosynthesis and

shedding of proTGF-a, a prototypical ligand of the Epidermal Growth Factor Receptor", Querétaro, Mexico,

November 18th 2001.

Plenary Lecture, 26th European Peptide Symposium. Títle: "Role of protein ectodomain shedding in biological

functions", Montpellier, France, September 13th 2000.

11th UK Adhesion Meeting. Title: "Protein ectodomain shedding in the absence of TACE", London, UK,

September 5th 2000. (Chairman of the session).

Gordon Research Conference on Matrix Metalloproteases. Title: “PDZ proteins and intracellular trafficking”,

New London, New Hampshire, USA, Agust 9th 1999.

Biochemical Society Meeting, Symposium on Membrane Protein Secretases. Title: "Mechanisms controlling the

shedding of transmembrane molecules", Leicester, U.K., September 27th1998.

Gordon Research Conference on Angiotensin. Title: “A common mechanism governing the shedding of

transmembrane proteins”, Il Ciocco, Italy, April 22nd 1997.

PROYECTOS

Terapias contra tumores de mama positivos para p95HER2 y senescencia celular inducida por p95HER2

Referencia: PI1202536

Instituto de Salud Carlos III

Referencia: PI1202536

Importe: 510.620 euros

Enero 2013-Diciembre 2015

Equipo investigador: Beatriz Morancho Armisen, Cristina Bernadó Morales, Kim Pedersen, Josep Lluis Parra

Palau, Pier Davide Angelini, Mariano Zacarias Fluck, Marta Escorihuela

Red Temática de Investigación Cooperativa

Referencia: RD12/0036/0042

Instituto de Salud Carlos III (Subdirección General de Redes y Centros de Investigación Cooperativa)

Importe: 92.575 euros

11

Enero 2013-Diciembre 2014

Equipo investigador: Beatriz Morancho Armisen, Octavio Cordoba Cardona, Josep Lluis Parra Palau, Pier Davide

Angelini, Roberto Rodriguez Revuelto, Isabel Teresa Rubio Rodriguez, Mariano Zacarias Fluck, Marta Escorihuela

Baez, Antonio Jesus Esgueva Colmenarejo, Tomas Cortadellas Rosell, Martin Espinosa Bravo

Envejecimiento celular prematuro y cáncer de mama. Papel de la metaloproteasa ADAM17

Fundación Sandra Ibarra

Importe: 25.000 €

Marzo 2013 – Febrero 2014

HER2-induced cellular senescence in breast cancer progression and treatment

Breast Cancer Research Foundation

Importe: 240.000 dólares

Octubre 2012-Octubre 2013

Equipo investigador: Kim Pedersen, Josep Lluís Parra Palau, Beatriz Morancho, Aniello Cerrato.

Nuevas estrategias para tratar el cáncer de mama positivo para HER2

Asociación Española Contra el Cáncer

Importe: 1.200.000 euros

Septiembre 2012-Septiembre 2017

Equipo investigador: Kim Pedersen, Josep Lluís Parra Palau, Beatriz Morancho Armisen, Aniello Cerrato, Mariano

Z. Fluck Zacarías, Agueda Martínez Barriocanal, Pier Davide Angelini, Rocio Vicario, Antonio Luque Garcia, Marta

Escorihuela Baez, Cristina Ferrer Ramón, Javier Cortés Castán, Isabel Rubio Rodriguez, Ludmila Prudkin, Ana

Vivancos Prellezo, Vicente Peg.

Tratamiento de la hiperactivación de HER2 en Cáncer de mama

AVON Cosmetics Foundation

Importe: 285.333 euros

Mayo 2012-Mayo 2015

Equipo investigador: Josep Tabernero Caturla, Aleix Prat Aparicio, Isabel Rubio Rodriguez, Francesc Canals,

Josep Lluis Parra Palau, Kim Pedersen, Beatriz Morancho Armisen, Joan Josep Bech Serra, Ludmila Prudkin,

Vicente Peg, Cristina Bernadó Morales, Antonio Luque García, Cristina Ferrer Ramón

Functional characterization of novel factors mediating the oncogenic activity of HER2. Role in the progression of

breast cancer

12

Breast Cancer Research Foundation

Importe: 500.000 dolares

Octubre 2010-Octubre 2012

Equipo investigador: Kim Pedersen, Josep Lluís Parra Palau, Beatriz Morancho Armisen, Aniello Cerrato, Pier

Davide Angelini, Cristina Bernadó Morales, Cristina Ferrer Ramón, Marta Escorihuela, Antonio Luque García.

Research Collaboration Agreement (Glaxo Smith Kline)

Glaxo Smith Kline

Importe: 500.000 dolares

Octubre 2009-Diciembre 2012

Equipo investigador: Kim Pedersen, Josep Lluís Parra Palau, Beatriz Morancho Armisen, Mariano Zacarías Fluck,

Pier Davide Angelini, Marta Escorihuela Baez

Novel factors and mechanisms mediating the oncogenic activity of HER2

Breast Cancer Research Foundation

Importe: 250.000 dólares

Octubre 2009-Octubre 2010

Equipo investigador: Kim Pedersen, Josep Lluís Parra Palau, Beatriz Morancho Armisen, Pier Davide Angelini,

Cristina Bernadó Morales, Cristina Ferrer Ramón, Antonio Luque Garcia.

Desarrollo tecnológico de anticuerpos monoclonales con interés diagnóstico y/o terapéutico contra el receptor

HER2 y/o sus variantes truncadas

Genoma España

Importe: 276.300 euros

Mayo 2009-Diciembre 2011

Equipo investigador: Josep Lluís Parra Palau, Marta Escorihuela

Ajuts de Suport a la Recerca. Grup de Recerca Consolidat

Agencia de Gestió d'Ajuts Universitaris i de Recerca

Referencia: 2009SGR328

Importe: 44.720 euros

Enero 2009-Enero 2014

13

Equipo investigador: Francesc Canals Suris, Kim Pedersen, Cary Esselens, Jordi Malapeira Argilaga, Josep Lluis

Parra Palau, Beatriz Morancho Armisen, Matthew Paul Cuningham, Mariano Zacarias Fluck, Veronica Calvo Vidal,

Pier Davide Angelini, Cristina Bernadó Morales, Cristina Ferrer Ramón, Antonio García Luque, Sandra Paola

Mancilla, Marta Escorihuela Baez, Silvia Corvinos Mezcua, Nuria Colomé Calls, Joan Josep Bech Serra, Marta

Monge Azemar, Sandra Porta Martínes, Susana Muñiz Lopez.

Fragmentos Carboxilo Terminales (CTFs) en la progresión y tratamiento de cáncer de mama

Instituto de Salud Carlos III

Referencia: PI081154

Importe: 794.970 euros

Enero 2009-Enero 2013

Equipo investigador: Kim Pedersen, Cary Esselens, Jesús Garcia Castillo, Sirle Laos, Josep Lluís Parra Palau,

Jordi Malapeira Argilaga, Matthew Paul Cunningham, Pier Davide Angelini, Maria Ines Barreto Das Neves Lopes

Texeira, Sandra Paola Mancilla, Cristina Ferrer Ramón, Antonio Miguel Luque García.

Metastasis in breast tumors expressing 611-CTF of HER2: mechanisms and therapeutic strategies

Breast Cancer Research Foundation

Importe: 250.000 dólares

Octubre 2008-Octubre 2009

Equipo investigador: Kim Pedersen, Josep Lluis Parra Palau, Sirle Laos, Mathew Paul Cunningham, Pier Davide

Angelini.

Referencia: RD06/0020/0022

Red Temática de Investigación Cooperativa

Instituto de Salud Carlos III (Subdirección General de REdes y Centros de Investigación Cooperativa)

Importe: 1.666.587 euros

Enero 2007-Diciembre 2012

Equipo investigador: Francesc Canals, Maria Belen Santiago Josefat, Kim Pedersen, Cary Esselens, Lluis Parra

Palau, Jordi Malapeira, Manel Garcia Medina, Matthew Paul Cuningham, Mariano Zacarias Fluck, Judit Anido

Folgueira, Pier Davide Angelini, Rocio Vicario, Cristina Bernadó, Cristina Ferrer Ramón, Antonio Miguel Luque

Garcia,

Identificación de mecanismos y factores involucrados en la sobreexpresión y tráfico intracelular de ADAM17

(TACE). Relevancia para el desarrollo de tumores de mama

Fundación Mutua Madrileña

Importe: 43.200 euros

14

Mayo 2007-Mayo 2010

Equipo investigador: Josep Baselga Torres, Francesc Canals, Cary Esselens, Jordi Malapeira, Ines Das Neves

Lopez Texeira, Cristina Ferrer Ramón, Joan Josep Bech Serra.

Identification of factors and mechanisms leading to metastasis in breast tumors expressing HER2 Carboxy

Terminal Fragments.

Breast Cancer Research Foundation

Importe: 250.000 dolares

Octubre 2007-Octubre 2008

Equipo investigador: Kim Pedersen, Jesus García Castillo, Josep Lluis Parra Palau, Sirle Laos, Matthew Paul

Cunningham, Pier Davide Angelini.

Ajuts de Suport a la Recerca. Grup de Recerca Consolidat

Agencia de Gestió d'Ajuts Universitaris i de Recerca

Referencia: 2005SGR00612

Importe: 36.600 euros

Enero 2006-Enero 2009

Equipo investigador: Francesc Canals, Javier Cortés Castán, Belen Santiago Josefat, Kim Pedersen, Cary

Esselens, Soraya Ruiz Paz, Joan Josep Bech Serra, Maria Teresa Villanueva de la Torre, Rosaura Esteve Puig,

Nuria Colomé Calls, Meritxell Bellet Ezquerra, Judit Balmaña Gelpi, Cristina Ferrer Ramón, Marta Guzman Torres,

Silvia Corvinos Mezcua

Generación y caracterización de ratones transgénicos expresando Fragmentos C-Terminales del oncogén HER2

en glándulas mamaria

Ministerio de Educación y Ciencia

Referencia: SAF2005-03939

Importe: 232.050 euros

Enero 2006-Enero 2009

Equipo investigador: Belen Santiago Josefat, Sirle Laos, Jesus Garcia Castillo, Cary Esselens, Judit Anido

Folgueira, Pier Davide Angelini, Antonio Garcia Luque.

Identificació i caracterització dels mecanismes de tumorogènesis mediats pels fragments carboxiterminals de

HER2.

Fundació la Marató TV3

Referencia: 05010

15

Importe: 248.750 euros

Enero 2006-Enero 2009

Equipo investigador: Kim Pedersen, Cary Esselens, Judit Anido Folgueira

Red Temática (FIS Puente)

Instituto de Salud Carlos III

Referencia: PI051658

Importe : 196.350 euros

Enero 2006-Diciembre 2006

Equipo investigador: Francesc Canals Suris, Joan Seoane Suarez, Sonia Martínez Arca, Cristina Ferrer

Ramón, Rachel Darken, Maria del Carmen Plaza Calonge, Antoni Xavier Torres Collado, Raquel Batlle

Gomez, Alexandra Arias Piñeiro, Miguel Hurtado Kuttner, Silvia Corvinos Mezcua, Sandra Porta Martínez,

Marta González Martínez, Nuria Colomé Calls

Caracterización funcional y estructural de un nuevo producto del proto-oncogén HER2. Implicaciones terapéuticas

en cáncer de mama

Asociación Española Contra el Cáncer

Importe: 300.000 euros

Febrero 2005- Febrero 2008

Equipo investigador: Belen Santiago Josefat, Kim Pedersen, Judit Anido Folgueira, Antonio Garcia Luque,

Marta Guzman Torres, Maria Goretti Mallorqui Fernandez, Noemí Mallorqui Fernandez

Identificación del degradoma de la metaloproteasa desintegrina TACE: relevancia en el desarrollo de tumores de

mama

La Caixa

Referencia: BM05-208-00

Importe: 137.000 euros

Mayo 2005 – Mayo 2008

Equipo investigador: Jose Baselga Torres, Federico Gustavo Rojo Todo, Francesc Canals Suris, Belens

Santiago Josefat, Cary Esselens, Jordi Malapeira Argilaga,Teresa Villanueva de la Torre, Joan Josep Bech

Serra.

Signalling and Membrane Trafficking in Transformation and Differentiation

STREP

Comisión Europea

16

Referencia: FP6-503228

Importe: 234.000 euros

Enero 2004-Diciembre 2006

Equipo investigador: Sonia Martinez Arca, Cary Esselens, Joan Josep Bech Serra, Pier Davide Angelini,

Rosaura Esteve Puig, Miguel Hurtado Kutner.

Genomica del Cáncer. Genotipado de tumores

Instituto de Salud Carlos III (Subdirección General de REdes y Centros de Investigación Cooperativa)

Referencia: C03/10

Importe : 1.002.319 euros

Enero 2003-Diciembre 2005

Equipo investigador: Nuria Colomé Calls, Cristina Ferrer Ramón, Silvia Corvinos Mezcua, Francesc Canals

Surís, Sandra Porta Martínez, Javier Hernández Losa, Marta González Martínez, Joan Seoane Suárez,

Rachel Darken, Raquel Batlle Gomez, Alexandra Arias Piñeiro,

Juan Carlos Rodriguez-Manzaneque Escribano, Maria del Carmen Plaza Calonge, Antoni Xavier Torres

Collado, Sonia Martínez Arca, Miguel Hurtado Kuttner, Rossana Paciucci Barzanti, Anna Santamaría

Margalef, Sandra Vila Muga, Miguel Abal Posada, Francina Munell Casadesus, Tomás Pinos Figueras,

Antoni Huratdo Rodriguez, Alba Segovia Corrales, Simó Schwartz Navarro, Manel Armengol Carrasco, Eloi

Espín Basany, Hafid Alazzouzi, Laura García Latorre, Jesus Planaguma Valls, Marta Monge Azemar, Javier

Cortés Castán, Joaquín Bellmunt Molins, Juan Carulla Torrent, Josep Tabernero Caturla, Enriqueta Felip

Font, Marta Guzman Torres, Serena Di Cosimo, Santiago Ramon y Cajal Agueras, Matilde Esther Lleonart

Pajarín, Federico Gustavo Rojo Todo, Carmela Iglesias Felip, Miriam Cuatrecasas Freixas, Maria Díaz

Fuertes

Ajuts de Suport a la Recerca. Grup de Recerca Consolidat

Agencia de Gestió d'Ajuts Universitaris i de Recerca

Referencia: 2002SGR00019

Importe: 48.000 euros

Enero 2003-Diciembre 2005

Acción Especial EMBO

Ministerio de Ciencia y Tecnología.

Referencia: 2001-5069-E

45.000 euros

Enero 2003- Diciembre 2003

17

Papel del shedding de los ligandos de receptores HER en el desarrollo y progresión tumoral

Referencia: PI021003

Importe: 51.175 euros

Enero 2003-Diciembre 2005

Caraterización e identificación de componentes de la maquinaria de transporte a la superficie celular de receptores

de glutamato NMDA

Fundación La Marató de TV3

Referencia: 01810

101.198,42 euros

Enero 2002-Diciembre 2004

Shedding of pro-Transforming Growth Factor-alpha role of metalloprotease-disintegrins and pro-protein

convertases

EMBO Young Investigator Programme.

Referencia: 450

Importe: 90.000 euros

Enero 2002-Diciembre 2004

Identificación y caracterización de la maquinaria de transporte de proTGF-alpha a la superficie celular

Comisión Interministerial de Ciencia Y Tecnología (CICYT)

Referencia: SAF2000-0203

Importe: 162.624 euros (27.104.000 pesetas)

Enero 2001-Diciembre 2003

Regulación de las Adamalisinas y la vía ubiquitina-proteasoma en el procesamiento proteolítico de la bAPP

Fundación la Caixa

Referencia: 99/0020-1

Importe: 51.750 euros (8.625.000 pesetas)

1998-2001

Papel de las Adamalisinas en la generación del péptido Ab

18

Fundación La Marató de TV3

Referencia: 036/97

Importe: 94.239 euros

1998-2001

Identificación y caraterización de la maquinaria de corte activado de factores de crecimiento de transmembrana

Comisión Interministerial de Ciencia Y Tecnología (CICYT)

Referencia: SAF97-0229

Importe: 113.022 euros (18.837.000 pesetas)

1997-2000

[Biosketch Marcos Malumbres] March 2013

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Marcos Malumbres, PhD

Head, Cell Division & Cancer Group, Molecular Oncology Program

Spanish National Cancer Research Centre (CNIO); http://www.cnio.es/ing/

http://malumbreslab.org

Work address: Melchor Fernandez Almagro 3 phone 34-91-732 8000

Madrid, E28029, SPAIN fax 34-91-732 8033 e-mail: malumbres@cnio.es

Education

1993 Ph.D., University of León, León, Spain

1987 B.S., University of Navarra, Pamplona

Research and Professional Experience

2005- Head, Cell Division & Cancer Group (CNIO)

2004- Staff Investigator, Spanish National Council of Research (CSIC), Spain

1999-2004 Staff Scientist, CNIO, Madrid. (Mariano Barbacid, Supervisor)

1995-1998 Assistant Research Scientist, New York University Medical Center, New York, USA, ( Angel Pellicer, Supervisor)

1993-1994 Postoctoral Fellow, New York University Medical Center, New York, USA, ( Angel Pellicer, Supervisor)

1988-1988 Visiting Scientist, Zentrum für Molekulare Biologie im Heidelberg ( Hermann Bujard, Supervisor)

1988-1993 Graduate Fellow, Dep. of Microbiology, Univ. of León, León, Spain (Juan F. Martín, Supervisor)

Awards and Honors

2007-2008 Council Member, European Association for Cancer Research 2007- Honorary member, Balkan Union of Oncology 2005 SEBBM Beckman/Coulter Award 2005 2001- Honorary Professor, Univ. Autónoma de Madrid 1994 “Juan Abelló” Prize of the Real Academia de Doctores

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Professional Society Memberships and Committees

2010- American Society of Microbiology 2009- ISCIII Animal Committee 2006-2008 CNIO Animal Committee 2001- European Association for Cancer Research 1998- Spanish Society of Biochemistry and Molecular Biology (SEBBM)

Teaching and Administrative Responsabilities

Post-graduate and doctoral coursers: Universidad Autónoma de Madrid, Universidad Complutense de Madrid, Univ. Del País Vasco (Bilbao), Gulbenkian Institute (Portugal), etc.

Peer-Review Activities

Editorial Boards 2007- J. BUON 2008- Current Medical Chemistry 2010- Molecular Cancer, Associate Editor 2010- Genes & Cancer, Editorial Board founding member, 2010 2011- Frontiers in Molecular and Cellular Oncology, Associate Editor 2011- microRNA, Editorial Board founding member, Journal Peer-Review Science, Nature Reviews series (Nat. Rev. Cancer, Nat. Rev. Mol. Cell Biol., Nat Rev. Drug Discover), Nat. Med., Nat. Cell Biol., Nat. Communications, Nat. Struc. Biol., Mol. Syst. Biol., Trends series, Cancer Cell, PLoS Biol., EMBO J., EMBO Reports, EMBO Mol. Med., J. Clin. Invest., PNAS, J. Nat. Cancer Inst., J. Cell Biol., Mol. Biol. Cell, Mol. Cell. Biol., Cancer Res., Oncogene, Nucleic Acids Res., Carcinogenesis, Cell Cycle, FEBS Letters, Bioessays and others. Grant Review Ad hoc reviewer for EU 7FP, Cancer Research UK, The Wellcome Trust, Association for International Cancer Research. Dutch Cancer Society, Research Grants Council (Hong Kong), INCA (France) and Spanish National (MICINN, FIS, AECC) and Regional (Cataluña, Junta Andalucía, Xunta Galicia, etc.) Institutions. Staff member of the Spanish Agency of Evaluation of Research Projects (ANEP; since 2012). Grant Committees Spanish Ministry of Innovation and Research (MICINN, 2001-2011), Ministry of Health (FIS 2006-2010), EU 7FP (2008), AECC (2007), Staff Spanish National Agency for Project Evaluation (ANEP; 2012-).

International Conferences Organized

CNIO Cancer Conference The Cell Cycle and Cancer, Centro Nacional de Investigaciones Oncológicas, Madrid, 2002 (co-organizers: Jiri Bartek, Charles J. Sherr)

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Workshop on Mouse Models in Cancer, Barcelona, 2004.b(co-organizer)

Cell Cycle and Cancer Meeting, Toulouse, March 2008 (organizing Committee).

Cell Cycle Regulators/Inhibitors & Cancer, Vienna, February 2011 (organizing Committee).

Aneuploidy and Chromosomal Instability and Cancer. CNIO, Madrid, 2013 (co-organizer)

Invited Conferences

(Representative conferences in the last 5 years)

2008 Cell Cycle and Cancer Meeting, Toulouse, France 2008 MRC Research Centre, Cambridge, UK 2008 10th European Congress of Endocrinology, Berlin, Germany 2008 MRC Clinical Sciences Center, London, UK 2009 Institute for Molecular Pathology, Vienna, Austria 2009 Baylor College of Medicine, Houston, USA 2009 AACR Annual Meeting, Denver, USA 2009 The First EMBO Meeting, Amsterdam, The Netherlands 2009 IRBB, ICC, Barcelona, Spain 2009 Gulbenkian Institute, Oeiras, Lisbon 2010 Centre de Recherche en Biochemie Macromoléculaire, Montpellier 2010 Chromosome segregation and Aneuploidy Symposium, IBMC, Porto, Lisbon 2011 Cell Cycle Inhibitors and Cancer Workshop, Vienna 2011 The Institute for Cancer Research, London 2011 Univ. Of Lisboa, Lisbon 2011 Cell Signaling Networks, Merida, México 2011 Inproteolysis 2011, Valencia 2011 Univ. P. Sabatier, Toulouse 2011 Nordisk Mitotic Network, Copenhagen 2012 Cancer Research Center (CIC) Salamanca 2012 Institute for Research in Immunology and Cancer (IRIC), Université de Montréal 2012 Jacques-Monod Conference of the Cell Cycle, Roscoff, 2012 2012 EMBO Workshop on Early Mouse Development, Cambridge, UK 2012 EMBL Monterontondo, Italy 2012 56th Nat. Meeting of the Italian Society of Biochemistry and Molecular Biology, Chieti 2013 EMBO Workshop, Cell Death in Mitosis meeting, Obergurgl, Austria 2013 AACR Annual Meeting, Washington

Patents

Bueno, M.J., Pérez de Castro, I., Fernández-Piqueras, J., Malumbres, M. (2008) Use of microRNA-203 for the manufacture of a medicament for treating cancer in humans and for

[Biosketch Marcos Malumbres] March 2013

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reducing V-abl Abelson murine leukemia viral oncogene homolog 1 (ABL1) and B cell receptor (BCR)-ABL1 expression and tumor cell proliferation. Patent Number(s): WO2009112625-A1; ES2325726-A1; ES2325726-B1 Alvárez, C., Diéguez, C., García-Lavandeira, M., Malumbres, M. (2008) Isolation of multipotent hypophysary cells and in vitro differentiation thereof. Pub. No.: WO/2010/061030. International Application No.: PCT/ES2009/070530

Publications

1. Malumbres, M., Mateos, L.M., Guerrero, C. and Martín, J.F. (1988) Nucleotide sequence of the threonine synthase (thrC) gene of Brevibacterium lactofermentum. Nucleic Acids Res. 16, 9859. [PMID: 3186450]

2. Martín, J.F., Cadenas, R.F., Malumbres, M., Mateos, L.M., Guerrero, C. and Gil, J.A. (1990) Construction and utilization of promoter-probe and expression vectors in corynebacteria. Characterization of corynebacterial promoters. In: Genetics of Industrial Microorganisms '90. Heslot, H., Davies, J., Florent, J., Bobichon, L., Durant, G., Penasse, L., eds. Société Francaise de Microbiologie, Strasbourg, pp. 283-292.

3. Martín, J.F., Mateos, L.M., Cadenas, R.F., Guerrero, C., Malumbres, M., Colina, A. and Gil, J.A. (1990) Molecular genetics of corynebacteria: cloning and characterization of the tryptophan operon and the genes of the threonine biosynthetic pathway. In: Microbiology Applications in Food Biotechnology. Nga, B.H., Lee, Y.K., eds. Elsevier, London, pp. 20-26.

4. Guerrero, C., Mateos, L.M., Malumbres, M. and Martín, J.F. (1992) The bleomycin resistance gene from Tn5 is an excellent marker for transformation of corynebacteria. Appl. Microbiol. Biotechnol. 36, 759-762. [PMID: 1373065]

5. Pisabarro, A., Malumbres, M., Mateos, L.M., Oguiza, J.A. and Martín, J.F. (1993) A cluster of three genes, dapA, orf2, and dapB, of Brevibacterium lactofermentum encodes dihydrodipicolinate synthase, dihydrodipicolinate reductase and a third polypeptide of unknown function. J. Bacteriol. 175, 2743-2749. [PMID: 8478336]

6. Malumbres, L. and Malumbres, M. (1993) Promoter structure recognition in corynebacterial DNA sequences by artificial neural networks. In: Industrial & Cognitive Applications of Neural Networks. EC2 Publishing, Nanterre, pp. 155-164.

7. Coque, J.J.R., Malumbres, M., Martín, J.F. and Liras, P. (1993) Analysis of the codon usage of the cephamycin C producer Nocardia lactamdurans. FEMS Microbiol. Lett. 110, 91-96.

8. Oguiza, J.A., Malumbres, M., Eriani, G., Pisabarro, A., Mateos, L.M., Gangloff, J. and Martín, J.F. (1993) A gene encoding arginyl-tRNA synthetase is located in the upstream region of the lysA gene in Brevibacterium lactofermentum: Regulation of the argS-lysA cluster expression by arginine. J. Bacteriol. 175, 7356-7362. [PMID: 8226683]

9. Malumbres, M., Gil, J.A. and Martín, J.F. (1993) Codon preference in corynebacteria. Gene 134, 15-24. [PMID: 8244028]

10. Guerrero, C., Mateos, L.M., Malumbres, M. and Martín, J.F. (1994) Directed mutagenesis of a regulatory palindromic sequence upstream from the Brevibacterium lactofermentum tryptophan operon. Gene 138, 35-41. [PMID: 7510262]

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11. Malumbres, M., Mateos, L.M., Lumbreras, M.A., Guerrero, C. and Martín, J.F. (1994) Analysis and expression of the thrC gene of Brevibacterium lactofermentum and characterization of the encoded threonine synthase. Appl. Environ. Microbiol. 60, 2209-2219. [PMID: 8074505]

12. Mateos, L.M., Pisabarro, A., Pátek, M., Malumbres, M., Guerrero, C., Eikmanns, B.J., Sahm, H. and Martín, J.F. (1994) Transcriptional analysis and regulatory signals of the hom-thrB cluster of Brevibacterium lactofermentum. J. Bacteriol. 176, 7362-7371. [PMID: 7961509]

13. Malumbres, M., Mateos, L.M. and Martín, J.F. (1995) Microorganisms for amino acid production: Escherichia coli and corynebacteria. In: Food Biotechnology: Microorganisms. Hui, Y.H., Khachatourians, G.G., eds. VCH Publishers, Inc, pp. 423-469.

14. Malumbres, M., Mateos, L.M., Guerrero, C. and Martín, J.F. (1995) Molecular cloning of the hom-thrC-thrB cluster from Bacillus sp. ULM1: Expression of the thrC gene in Escherichia coli and corynebacteria, and evolutionary relationships of the threonine genes. Folia Microbiol. 40, 595-606. [PMID: 8768250]

15. Oguiza, J.A., Marcos, A.T., Malumbres, M. and Martín, J.F. (1996) Multiple sigma factor genes in Brevibacterium lactofermentum: characterization of sigA and sigB. J. Bacteriol. 178, 550-553. [PMID: 8550480]

16. Malumbres, M. and Martín, J.F. (1996) Molecular control mechanisms of lysine and threonine biosynthesis in amino acid-producing corynebacteria: Redirecting carbon flow. FEMS Microbiol. Lett. 143, 103-114. [PMID: 8837462]

17. Oguiza, J.A., Marcos, A.T., Malumbres, M. and Martín, J.F. (1996) Sequence and transcriptional analysis of the galE gene encoding the UDP-galactosidase of Brevibacterium lactofermentum. Gene 177, 103-107. [PMID: 8921853]

18. Malumbres, M., Pérez de Castro, I., Santos, J., Meléndez, B., Mangues, R., Serrano, M., Pellicer, A. and Fernández-Piqueras, J. (1997) Inactivation of the cyclin-dependent kinase inhibitor p15INK4b by deletion and de novo methylation with independence of p16INK4a alterations in murine primary T-cell lymphomas. Oncogene 14, 1361-1370. [PMID: 9178896]

19. Malumbres, M., Mangues, R., Ferrer, N., Lu, S. and Pellicer, A. (1997) Isolation of high molecular weight DNA for reliable genotyping of transgenic mice. BioTechniques 22, 1114-1119. [PMID: 9187761]

20. Malumbres, M., Perez de Castro, I., Santos, J., Perez-Olle, R., Fernandez-Piqueras, J. and Pellicer, A. (1998) An AC-repeat adjacent to mouse Cdkn2B allows the detection of specific allelic losses in the p15INK4b and p16INK4a tumor suppressor genes. Mamm. Genome 9, 183-185. [PMID: 9501299]

21. Mangues, R., Corral, T., Kohl, N.E., Symmans, W.F., Lu, S., Malumbres, M., Gibbs, J.B., Oliff, A. and Pellicer, A. (1998) Antitumor effect of a farnesyl-protein transferase inhibitor in mammary and lymphoid tumors overexpressing N-ras in transgenic mice. Cancer Res. 15, 1253-1259. [PMID: 9515813]

22. Malumbres, M. and Pellicer, A. (1998) Ras pathways to cell cycle control and cell transformation. Front. Biosci. 3, d887-912. [PMID: 9696882]

23. Malumbres, M., Pérez de Castro, I., Santos, J., Fernández-Piqueras, J. and Pellicer, A. (1999) Hypermethylation of the cell cycle inhibitor p15INK4b 3’-untranslated region interferes with its transcriptional regulation in primary lymphomas. Oncogene 18, 385-396. [PMID: 9927195]

24. Malumbres, M. and Pellicer, A. (1999) Ras signaling in cell cycle regulation and its role in tumor development. Rev. Oncologia 1, 66-76.

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25. Pérez de Castro, I., Malumbres, M., Santos, J., Pellicer, A. and Fernández-Piqueras, J. (1999) Cooperative alterations of Rb-pathway regulators in mouse primary T-cell lymphomas. Carcinogenesis 20, 1675-1682. [PMID: 10469610]

26. García-España, A., Biria, S., Malumbres, M., Levin, B., Meruelo, D. and Pellicer, A. (1999) Targeted gene transfer system using a streptavidine-transforming growth factor-a chimeric protein. DNA Cell Biol. 18, 743-749. [PMID: 10541433]

27. Pellicer, A. and Malumbres, M. (2000) Bases moleculars de la transformacio neoplasica. In: Llicons de Patologia Molecular, González-Sastre, F. and Guinovart, J.J., eds. Springer-Verlag, Heidelberg, Barcelona.

28. Meléndez, B.*, Malumbres, M.*, Pérez de Castro, I., Santos, J., Pellicer, A. and Fernández-Piqueras, J. (2000) Characterization of the murine p19ARF promoter CpG island and its methylation pattern in primary lymphomas. Carcinogenesis 21, 817-821. [PMID: 10753221]

29. Malumbres, M., Pérez de Castro, I., Hernández, M.I., Jiménez, M., Corral, M.T. and Pellicer, A. (2000) Cellular response to oncogenic Ras involves induction of the Cdk4 and Cdk6 inhibitor p15INK4b. Mol. Cell. Biol., 20, 2915-2925. [PMID: 10733595]

30. Hernández-Muñoz, M.I., Malumbres, M., Leonardi, P. and Pellicer, A. (2000) The Rgr oncogene (homologous to RalGDS) induces transformation and gene expression by activating Ras, Ral and Rho mediatedpathways. Oncogene, 19, 2745-2757. [PMID: 10851075]

31. Latres, E., Malumbres, M., Sotillo, R., Martín, J., Ortega, S., Martín-Caballero, J., FLores, J.M., Cordon-Cardo, C. and Barbacid. M. (2000) Limited overlapping roles of P15INK4b and P18INK4c cell cycle inhibitors in proliferation and tumorigenesis. EMBO J., 19, 3496-3506.

32. Malumbres, M., Ortega, S. and Barbacid, M. (2000) Genetic analysis of cyclin-dependent kinases and their inhibitors. Biol. Chem., 381, 827-838.

33. Esteban, L.M., Vicario-Abejon, C., Fernandez-Salguero, P., Fernandez-Medarde, A., Swaminathan, N., Yienger, K., Lopez, E., Malumbres, M., McKay, R., Ward, J.M., Pellicer, A., Santos, E. (2001) Targeted genomic disruption of H-ras and N-ras, individually or in combination, reveals the dispensability of both loci for mouse growth and development. Mol. Cell. Biol. 21, 1444-1452.

34. Sotillo, S., Dubus, P., Martín, J., de la Cueva, E., Ortega, S., Malumbres, M. and Barbacid, M. (2001) Wide spectrum of tumors in knock in mice carrying a Cdk4 protein insensitive to INK4 inhibitors. EMBO J. 20, 6637-6647.

35. Sotillo, R., García, J. F., Ortega, S., Martín, J., Dubus, P., Barbacid, M and Malumbres M. (2001) Invasive melanoma in Cdk4 targeted mice. Proc. Natl. Acad. Sci. USA 98, 13312-13317.

36. Malumbres, M. and Barbacid, M. (2001) To cycle or not to cycle: a critical decision in cancer. Nature Reviews Cancer 1, 222-231.

37. Ortega, S., Malumbres, M. and Barbacid, M. (2002) Cdk4 and their INK4 inhibitors in tumor biology. Biochim. Biophys. Acta 87513, 1-15.

38. Diaz, R., Ahn, D., Lopez-Barcons, L., Malumbres, M., Pérez de Castro, I., Lue, J., Ferrer, N., Mangues, R., Tsong, J., García, R., Pérez-Soler, R. and Pellicer, A. (2002) The N-ras protooncogene can suppress the malignant phenotype in the presence or absence of its oncogene. Cancer Res. 62, 4514-4518.

39. Ortega, S., Malumbres, M. and Barbacid, M. (2002) Cell cycle and Cancer: The G1 restriction point and the G1/S transition. Curr. Genomics 3, 245-263.

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40. Malumbres, M. and Carnero, A. (2003) Cell cycle deregulation: a common motif in cancer. Progress Cell Cycle Res. 5, 5-18.

41. Pérez de Castro, I., Diaz, R., Malumbres, M., Hernández, M.I., Jagirdar, J., Jiménez, M., Ahn, D. and Pellicer A. (2003) Mice deficient for N-ras: Impaired antiviral immune response and T-cell function. Cancer Res. 63, 1615-1622.

42. Malumbres, M. and Barbacid, M. (2003) RAS oncogenes: the first 30 years. Nature Rev. Cancer 3, 459-465.

43. Malumbres, M., Hunt, S.L., Sotillo, R., Martín, J., Odajima, J., Martín, A., Dubus, P., Ortega, S., Barbacid, M. (2003) Driving the cell cycle to cancer. Adv. Exp. Med. Biol. 532, 1-11.

44. Martín, J., Hunt, S.L., Dubus, P., Sotillo, R., Néhmé-Pélluard, F., Magnuson, M.A., Parlow, A.F., Malumbres, M., Ortega, S. and Barbacid, M. (2003) Genetic rescue of Cdk4 null mice restores pancreatic -cell proliferation but not homeostatic cell number. Oncogene 22, 5261-5269.

45. Ortega, S., Prieto, I., Odajima, J., Martín, A., Dubus, P., Sotillo, R., Barbero, J.L., Malumbres, M. and Barbacid, M. (2003) Cyclin dependent kinase 2 is essential for meiosis but not for mitotic cell division in mice. Nature Genet. 35, 25-31.

46. Wolff, L., Garin, M.T., Koller, R., Bies, J., Liao, W., Malumbres, M., Tessarollo, L., Powell, D. and Perella, C. (2003) Hypermethylation of the Ink4b Locus in Murine Myeloid Leukemia and Increased Susceptibility to Leukemia in p15Ink4b-deficient Mice. Oncogene 22, 9265-9274.

47. Malumbres, M.*, Sotillo, R., Santamaría, D., Galán, J., Cerezo, A., Ortega, S., Dubus, P. and Barbacid, M.* (2004) Mammalian cells cycle without the D-type cyclin-dependent kinases Cdk4 and Cdk6. Cell 118, 493-504. [*Co-corresponding authors]

News & Views: Murray, A.W. (2004) Recycling the cell cycle: cyclins revisited. Cell 116, 221-234. Cycling without cyclins. The Scientist, August 20, 2004.

48. Auwerx, J., Avner, P., Baldock, R., Ballabio, A., Balling, R., Barbacid, M., Berns, A., Bradley, A., Brown, S., Carmeliet, P., Chambon, P., Cox, R., Davidson, D., Davies, K., Duboule, D., Forejt, J., Granucci, F., Hastie, N., Hrabé de Angelis, M., Jackson, I., Kioussis, D., Kollias, K., Lathrop, M., Lendahl, U., Malumbres, M., Melchner, H. von, Müller, W., Partanen, J., Ricciardi-Castagnoli, P., Rigby, P., Rosen, B., Rosenthal, N., Skarnes, B., Stewart, A.F., Thornton, J., Tocchini-Valentini, G., Wagner, E., Wahli, W. and Wurst, W. (2004) The European dimension for the mouse genome mutagenesis program. Nat. Genet. 36, 925-927.

49. Malumbres, M. (2005) Revisiting the “Cdk-centric” view of the mammalian cell cycle. Cell Cycle 4, 206-210.

50. Pérez de Castro, I., Benet, M., Jiménez, M., Alzabin, S., Malumbres, M. and Pellicer, A. (2005) Mouse p10, an alternative spliced form of p15INK4b, inhibits cell cycle progression and malignant transformation. Cancer Res., 65, 3249-3256.

51. Sotillo, R., Renner, O., Dubus, P., Ruiz-Cabello, J., Martín-Caballero, J., Barbacid, M., Carnero, A. and Malumbres, M. (2005) Cooperation Between Cdk4 and p27Kip1 in Tumor Development: a Preclinical Model to Evaluate Cell Cycle Inhibitors with Therapeutic Activity. Cancer Res., 65, 3846-3852.

52. Martín, A., Odajima, J., Hunt, S.L., Dubus, P., Ortega, S., Malumbres, M.* and Barbacid, M.* (2005) Cell Cycle Inhibition and Tumor Suppression by p21Cip1 and p27Kip1 are Independent of Cdk2. Cancer Cell 7, 591-598. [*Co-corresponding authors]

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53. Abella, A., Dubus, P., Malumbres, M., Rane, S.G., Kiyokawa, H., Sicard, A., Vignon, F., Langin, D., Barbacid, M. and Fajas, L. (2005) Cdk4 promotes adipogenesis through PPARgamma activation. Cell Metabolism 2, 239-249.

54. Malumbres, M. and Barbacid, M. (2005) Mammalian cyclin-dependent kinases. Trends Biochem. Sci., 30, 630-641.

55. Barbacid, M., Ortega, S., Sotillo, R., Odajima, J., Martín, A., Santamaría, D., Dubus, P. and Malumbres, M. (2005) Cell cycle and cancer: genetic analysis of the role of cyclin-dependent kinases. Cold Spring Harb. Symp. Quant. Biol. 70, 233-240.

56. Steitz, J., Büchs, S., Tormo, D., Ferrer, A., Wenzel, J., Huber, C., Wölfel, T., Barbacid, M., Malumbres, M. and Tüting, T. (2006) Evaluation of genetic melanoma vaccines in cdk4-mutant mice provides evidence for immunological tolerance against authochthonous melanomas in the skin. Int. J. Cancer 118, 373-380.

57. Duensing, A., Liu, Y., Tseng, M., Malumbres, M., Barbacid, M. and Duesing, S. (2006) Cyclin-dependent kinase 2 is dispensable for normal centrosome duplication but required for oncogene-induced centrosome overduplication. Oncogene 25, 2943-2949.

58. Malumbres, M., Dubus, P. and Ortega, S. (2006) Mouse models to study the in vivo function of Cyclin-dependent kinases in normal homeostasis and tumor development. In: Inhibitors of cyclin-dependent kinases as anti-tumor agents (Smith, P.J. and Yue, E.W., eds.) CRC Press, Boca Raton. pp. 55-83.

59. Malumbres, M. and Barbacid, M. (2006) Is Cyclin D1/Cdk4 kinase a bona-fide cancer target? Cancer Cell 9, 2-4.

60. Hacker, E., Muller, H.K., Irwin, N., Gabrielli, B., Lincoln, D., Pavey, S., Powell, M.B., Malumbres, M., Barbacid, M., Hayward, N. and Walker, G. (2006) Spontaneous and UV radiation-induced multiple metastatic melanomas in Cdk4R24C/R24C/TPras mice. Cancer Res. 66, 2946-2952.

61. Malumbres, M. (2006) Therapeutic opportunities to control tumor cell cycles. Clin. Transl. Oncol. 8, 399-408.

62. Tormo, D., Ferrer, A., Gaffal, E., Wenzel, J., Basner-Tschakarjan, E., Steitz, J., Heukamp, L.C., Gutgemann, I., Buettner, R., Malumbres, M., Barbacid, M., Merlino, G., Tuting, T. (2006). Rapid Growth of Invasive Metastatic Melanoma in Carcinogen-Treated Hepatocyte Growth Factor/Scatter Factor-Transgenic Mice Carrying an Oncogenic CDK4 Mutation. Am. J. Pathol. 169, 665-672.

63. Blazquez, C., Carracedo, A., Barrado, L., Real, P.J., Fernández-Luna, J.L., Velasco, G., Malumbres, M. and Guzman, M. (2006) Cannabinoid receptors as novel targets for the treatment of melanoma. FASEB J. 20, 2633-2635.

64. Malumbres, M. (2006) Preclinical models for cell cycle-targeted therapies. Adv. Exp. Med. Biol. 587, 139-147.

65. Malumbres, M. and Barbacid, M. (2007) Cell cycle kinases in cancer. Curr. Opin. Genet. Dev. 17, 60-65.

66. Pérez de Castro, I., de Cárcer, G. and Malumbres, M. (2007) A census of mitotic cancer genes. New insights into tumor cell biology and cancer therapy. Carcinogenesis 28, 899-912.

67. de Cárcer, G.; Pérez de Castro, I. and Malumbres, M. (2007) Targeting cell cycle kinases for cancer therapy. Curr. Med. Chem. 14, 969-985.

68. Cascón, A.,* Escobar, B.,* Montero-Conde, C., Rodríguez-Antona, C., Ruiz-Llorente, S., Osorio, A., Mercadillo, F., Letón, R., de Campos, J.M., García-Sagredo, J.M., Benítez, J., Malumbres,

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M. and Robledo, M. (2007) Loss of the actin regulator HSPC300 results in clear cell renal cell carcinoma protection in Von Hippel-Lindau patients. Hum. Mutat. 28, 613-621. [* Co-corresponding authors].

69. Barrière, C., Santamaría, D., Cerqueira, A., Galán, J., Martín, A., Ortega, S., Malumbres, M., Dubus, P. and Barbacid, M. (2007) Mice thrive without Cdk4 and Cdk2. Mol. Oncol. 1, 72-83.

70. Quereda, V., Martinalbo, J., Dubus, P., Carnero, A. and Malumbres, M. (2007) Genetic cooperation between p21Cip1 and INK4 inhibitors in cellular senescence and tumor suppression. Oncogene 26, 7665-7674.

71. Malumbres, M. (2007) Cyclin-dependent kinases and their regulators as potential targets for anticancer therapeutics. In: Principles of Molecular Oncology, Bronchud, ed. Humana Press, pp. 204-235.

72. Santamaría, D., Barrière, C., Cerqueira, A., Hunt, S.L., Tardy, C., Newton, K., Cáceres, J.F., Dubus, P., Malumbres, M. and Barbacid, M. (2007) Cdk1 is sufficient to drive the mammalian cell cycle. Nature 448, 811-815. [PMID: 17700700]

73. Malumbres, M. (2007) Cyclins and related kinases in cancer cells. J. BUON 12, S45-S52. [PMID: 17935277]

74. Malumbres, M., Pevarello, P., Barbacid, M. and Bischoff, J.R. (2008) CDK inhibitors in cancer therapy: What is next? Trends Pharmacol Sci. 29, 16-21. [PMID: 18054800]

Fast Moving Fronts paper in the field of Pharmacology & Toxicology (2010). http://sciencewatch.com/dr/fmf/2010/10julfmf/10julfmfMalu/

75. Bueno, M.J., Pérez de Castro, I., Gómez de Cedrón, M., Santos, J., Calin, G.A., Cigudosa, J.C., Croce, C.M., Fernández-Piqueras, J. and Malumbres, M. (2008) Genetic and Epigenetic Silencing of microRNA-203 Enhances ABL1 and BCR-ABL1 Oncogene Expression. Cancer Cell 13, 496-506. [PMID: 18538733]

News & Views: Faber, J., Gregory, R.I. and Armstrong, A.S. (2008) Linking miRNA regulation to BCR-ABL expression: the next dimension. Cancer Cell 13, 467-469.

76. García-Higuera, I., Manchado, E., Dubus, P., Cañamero, M., Mendez, J., Moreno, S. and Malumbres, M. (2008) Genomic Stability and Tumor Suppression by the APC/C Cofactor Cdh1. Nat. Cell Biol. 10, 802-811. [PMID: 18552834]

News & Views: Skaar, J.R. and Pagano, M. (2008) Cdh1: a master G0/G1 regulator. Nat. Cell Biol. 10, 755-757.

Faculty of 1000 Biology: evaluations for García-Higuera I et al Nat Cell Biol 2008 Jul 10 (7) :802-11 http://www.f1000biology.com/article/id/1120229/evaluation.

77. Pérez de Castro, I., de Cárcer, G., Montoya, G. and Malumbres, M. (2008) Emerging cancer therapeutic opportunities by inhibiting mitotic kinases. Curr. Opin. Pharmacol. 8, 375-383. [PMID: 18644252]

78. Bueno, M.J., Pérez de Castro, I. and Malumbres, M. (2008). Control of cell proliferation pathways by microRNAs. Cell Cycle 7, 3143-3148. [PMID: 18843198]

79. Infante, A., Laresgoiti, U., Fernández-Rueda, J., Fullaondo, A., Galán, J., Díaz-Uriarte, R., Malumbres, M., Field, S.J. and Zubiaga, A.M. (2008) E2F2 Represses Cell Cycle Regulators to Maintain Quiescence. Cell Cycle 7, 3915-3927. [PMID: 19066456]

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80. Quereda, V., and Malumbres, M. (2009) Cell Cycle Control of Pituitary Development and Disease. J. Mol. Endocrinol. 42, 75-86. [PMID: 18987159]

81. Muñoz, P., Blanco, R., de Carcer, R., Schoeftner, S., Benetti, R., Flores, J.M., Malumbres, M. and Blasco, M.A. (2009) TRF1 controls telomere length and mitotic fidelity in epithelial homeostasis. Mol. Cell. Biol. 29, 1608-1625. [PMID: 19124610]

82. Malumbres, M. and Barbacid, M. (2009) Cell cycle, CDKs and cancer: a changing paradigm. Nat. Rev Cancer 9, 153-166. [PMID: 19238148]

83. Garcia-Lavandeira, M., Quereda, V., Flores, I., Saez, C., Diaz-Rodriguez, E., Japon, M.A., Ryan, A.K., Blasco, M.A., Dieguez, C., Malumbres, M.* and Alvarez, C.V.* (2009) A GRFa2/Prop1/Stem (GPS) Cell Niche in the Pituitary. PLoS One 4, e4815. [PMID: 19283075] [* Co-corresponding authors].

84. Malumbres, M.,* Edward Harlow, Tim Hunt, Tony Hunter, Jill M. Lahti, Gerard Manning, David O. Morgan, Li-Huei Tsai, and Debra J. Wolgemuth (2009) Cyclin-dependent kinases: a family portrait. Nat. Cell Biol. 11, 1275-1276. [PMID: 19884882] [*Corresponding author]

85. Gurden, M.D.J., Holland, A.J., van Zon, W., Tighe, A., Vergnolle, M.A., Andres, D.A., Spielmann, H.P., Malumbres, M., Wolthuis, R.M.F., Cleveland, D.W. and Taylor, S.S. (2010) Cdc20 is required for the post-anaphase, KEN-dependent degradation of centromere protein F. J. Cell. Sci. 123, 321-330. [PMID: 20053638]

86. Manchado, E., Eguren, M. and Malumbres, M. (2010) The anaphase promoting complex/cyclosome (APC/C): cell-cycle-dependent and -independent functions. Biochem. Soc. Trans. 38, 65-71. [PMID: 20074037]

87. Bueno, M.J., Gómez de Cedrón, M., Laresgoiti, U., Fernández-Piqueras, J., Zubiaga, A. and Malumbres, M. (2010) Multiple E2F-induced microRNAs prevent replicative stress in response to mitogenic signalling. Mol. Cell. Biol. 30, 2983-2995. [PMID: 20404092]

88. Mourón, S., de Cárcer, G., Seco, E., Fernández-Miranda, G., Malumbres, M. and Nebreda, A.R. (2010) RINGO/Speedy C is required to sustain the spindle assembly checkpoint. J. Cell Sci. 123, 2586-2595. [PMID: 20605920]

89. Fernández-Miranda, G., Pérez de Castro, I., Carmena, M., Aguirre-Portolés, C., Ruchaud, S., Fant, X., Montoya, G., Earnshaw, W.C. and Malumbres, M. (2010) Modulation of Aurora B function by SUMOylation. J. Cell Sci. 123, 2823-2833. [PMID: 20663916]

90. Escobar, B., de Cárcer, G., Fernández-Miranda, G., Cascón, A., Bravo-Cordero, J.J., Montoya, M.C., Robledo, M., Cañamero, M. and Malumbres, M. (2010) Brick1 is an essential regulator of actin cytoskeleton required for embryonic development and cell transformation. Cancer Res. 70, 9349-9359. [PMID: 20861187].

91. Santibanez, J.F., Pérez-Gómez, E., Fernandez-L, A., Garrido-Martín, E., Carnero, A., Malumbres, M., Vary, C.P.H., Quintanilla, M. and Bernabéu, C. (2010) The TGF-β co-receptor endoglin modulates the expression and transforming potential of H-Ras. Carcinogenesis 31, 2145-2154. [PMID: 20884686]

92. Manchado, E., Guillamot, M., de Cárcer, G., Eguren, M., Trickey, M., García-Higuera, I., Moreno, S., Yamano, H., Cañamero, M. and Malumbres, M. (2010) Targeting mitotic exit leads to tumor regression in vivo: modulation by Cdk1, Mastl, and the PP2A/B55, phosphatase. Cancer Cell 18, 641-654. [PMID: 21156286]

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93. Muñoz, I.G., Yébenes, H., Zhou, M., Mesa, P., Serna, M., Park, A.Y., Bragado-Nilsson, E., Beloso, A., de Cárcer, G., Malumbres, M., Robinson, C.V., Valpuesta, J.M. and Montoya, G. (2011) Crystal structure of the open conformation of the mammalian chaperonin CCT in complex with tubulin. Nat. Struct. Mol. Biol. 18, 14-19. [PMID: 21151115]

94. Song, M.S., Carracedo, A., Salmena, L., Song, S.J., Egia, A., Malumbres, M. and Pandolfi, P.P. (2011) Nuclear PTEN regulates the APC-CDH1 tumor-suppressive complex in a phosphatase-independent manner. Cell 144, 187-199. [PMID: 21241890]

95. de Cárcer, G., Escobar, B., Higuero, A., García, L., Ansón, A., Pérez, G., Mollejo, M., Manning, G., Melendez, B., Abad-Rodriguez, J. and Malumbres, M. (2011) Plk5, a Polo-box domain-only protein with specific roles in neuron differentiation and glioblastoma suppression. Mol. Cell. Biol. 31, 1225-1239. [PMID: 21245385]

Selected for Mol. Cell. Biol. Spotlights. Extra-View in Cell Cycle 10 (2011) Seleced by Targe Intelligence Service (https://www.targetintelligenceservice.com/main/public/case.jsp?report_id=44541)

96. Kollmann, K., Heller, G., Ott, R.G., Scheicher, R., Zebedin-Brandl, E., Schneckenleithner, C., Simma, O., Warsch, W., Eckelhart, E., Hoelbl, A., Bilban, M., Zöchbauer-Müller, S., Malumbres, M. and Sexl, V. (2011) C-JUN promotes BCR-ABL induced lymphoid leukemia by inhibiting methylation of the 5’ region of Cdk6. Blood 117, 4065-4075. [PMID: 21300982]

97. Bueno, M.J. and Malumbres, M. (2011) microRNAs and the cell cycle. Biochim. Biophys. Acta 1812, 592-601. [PMID: 21315819]

98. Manchado, E. and Malumbres, M. (2011) Targeting aneuploidy for cancer therapy. Cell 144, 465-466. [PMID: 21335229]

99. Bueno, M.J., Gómez de Cedrón, M., Gómez-López, G., Pérez de Castro, I., di Lisio, L., Montes, S., Martínez, N., Guerrero, M., Sánchez, R., Santos, J., Pisano, D.G., Piris, M.A., Fernández-Piqueras, J. and Malumbres, M. (2011) Combinatorial effects of microRNAs to suppress the Myc oncogenic pathway. Blood 117, 6255-6266. [PMID: 21478429]

100. Eguren, M., Manchado, E. and Malumbres, M. (2011) Non-mitotic functions of the Anaphase-Promoting Complex. Semin. Cell Dev. Biol. 22, 572-578. [PMID: 21439391]

101. Chiesa, M.,* Guillamot, M.,* Bueno, M.J. and Malumbres, M. (2011) The Cdc14B phosphatase displays oncogenic activity mediated by the Ras-Mek signaling pathway. Cell Cycle 10, 1607-1617. [PMID: 21502810]

News and Views: Wei, Z & Zhang, P. A phosphatase turns aggressive: The oncogenicity of Cdc14B. Cell Cycle 10, 2414-2415; Visintin, R. Cdc14B: When a good kid turns bad. Cell Cycle 10, 2416-2417.

102. Fernández-Miranda, G., Trakala, M., Martín, J., Escobar, B., González, A., Ghyselinck, N.B., Ortega, S., Cañamero, M., Pérez de Castro, I. and Malumbres, M. (2011) Genetic disruption of Aurora B uncovers an essential role for Aurora C during early mammalian development. Development 138, 2661-2672. [PMID: 21613325]

103. Malumbres, M. (2011) Oncogene-induced mitotic stress: p53 and pRb get Mad too. Cancer Cell 19, 691-692. [PMID: 21665141]

104. de Cárcer, G., Manning, G. and Malumbres, M. (2011) From Plk1 to Plk5: functional evolution of Polo-like kinases. Cell Cycle 10, 2255-2262. [PMID: 21654194]

105. Malumbres, M. (2011) Physiological relevance of cell cycle kinases. Physiol. Rev. 91, 973-1007. [PMID: 21742793]

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106. Santamaría, D. and Malumbres, M. (2011) Tumor suppression by Spinophilin. Cell Cycle 10, 2831-2832. [PMID: 21869595]

107. Pérez de Castro, I., Aguirre-Portolés, C., Martin, B., Fernández-Miranda, G., Klotzbucher, A., Kubbutat, M.H.G., Megías, D., Arlot-Bonnemains, Y. and Malumbres, M. (2011) A SUMOylation Motif in Aurora-A: Implications in Spindle Dynamics and Oncogenesis. Front. Oncol. 1, 50. [PMID: 22649767]

108. Wan, L., Zou, W., Gao, D., Inuzuka, Fukushima, H., Berg, A.H., Drapp, R., Shaik, S., Hu, D., Lester, C., Eguren, M., Malumbres, M., Glimcher, L.H. and Wei, W. (2011) Cdh1 Regulates osteoblast function through an APC/C-independent modulation of Smurf1. Mol. Cell 44, 721-733. [PMID: 22152476]

109. Guillamot, M., Manchado, E., Chiesa, M., Gómez-López, G., Pisano, D.G., Sacristán, M. and Malumbres, M. (2011) Cdc14b regulates mammalian RNA polymerase II and represses cell cycle transcription. (Nature) Sci. Reports 1, 189. DOI:10.1038/srep00189. [PMID: 22355704]

110. Manchado, E., Guillamot, M. and Malumbres, M. (2012) Killing cells by targeting mitosis. Cell Death Differ. 19, 369-377. doi: 10.1038/cdd.2011.197 [PMID: 22223105]

111. Malumbres, M. (2012) miRNAs versus oncogenes: the power of social networking. Mol. Syst. Biol. 8, 569. doi: 10.1038/msb.2012.2 [PMID: 22333973]

112. Aguirre-Portolés, A., Bird, A.W., Hyman, A., Cañamero, M., Pérez de Castro, I. and Malumbres, M. (2012) Tpx2 controls spindle integrity, genome stability and tumor development. Cancer Res. 72, 1518-1528. [PMID: 22266221]

113. de Cárcer, G., Pérez de Castro, I. and Malumbres, M. (2012) Inhibiting cell cycle kinases in cancer therapy. Front. Med. Chem. 6, in press.

114. Malumbres, M. (2012) Cell cycle-based therapies move forward. Cancer Cell 22, 419-420. [PMID: 23079651]

115. Elorza, A., Soro-Arnáiz, I., Meléndez-Rodríguez, F., Rodríguez-Vaello, V., Marsboom, G., de Cárcer, G., Acosta-Iborra, B., Albacete-Albacete, L., Ordóñez, A., Serrano-Oviedo, L., Giménez-Bachs, J.M., Vara-Vega, A., Salinas, A., Sánchez-Prieto, R., Martín del Río, R., Sánchez-Madrid, F., Malumbres, M., Landázuri, M.O., Aragonés, J. (2012) HIF2 acts as an mTORC1 activator through the amino acid carrier SLC7A5. Mol. Cell 48, 681-691. [PMID: 23103253]

116. Parrillas, V., Martínez-Muñoz, L., Holgado, B.L., Kumar, A., Cascio, G., Lucas, P., Rodríguez-Frade, J.M., Malumbres, M., Carrera, A.C., van Wely, K.H., Mellado, M. (2013) Suppressor of cytokine signaling 1 blocks mitosis in human melanoma cells. Cell. Mol. Life Sci. 70, 545-558. [PMID: 23001011]

117. Pick, J.E., Malumbres, M. & Klann, E. (2013) The E3 ligase APC/C-Cdh1 is required for associative fear memory and long-term potentiation in the amygdala of adult mice. Learning & Memory 20, 11-20. [PMID: 23242419]

118. González-Gugel, E., Villa-Morales, M., Santos, J., Bueno, M.J., Malumbres, M., Rodríguez-Pinilla, S.M., Piris, M.A. and Fernández-Piqueras, J. (2013) Down-regulation of specific miRNAs enhances the expression of the gene Smoothened and contributes to T-cell lymphoblastic lymphoma development. Carcinogenesis, in press. [PMID: 23288923]

119. Pérez de Castro, I. and Malumbres, M. (2013) Mitotic stress and chromosomal instability in cancer: the case for TPX2. Genes & Cancer, in press.

120. Malumbres, M. (2013) miRNAs and cancer: An epigenetics view. Mol. Aspects Med. Jul 4. doi: 10.1016/j.mam.2012.06.005 [PMID: 22771542]

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121. Trakala, M., Fernández-Miranda, G., Pérez de Castro, I., Heeschen, C. and Malumbres, M. (2013) Aurora B prevents delayed DNA replication and premature mitotic exit by repressing p21Cip1. Cell Cycle, in press.

122. Doménech, E. and Malumbres, M. (2013) Mitosis-targeting therapies: a troubleshooting guide. Curr. Opin. Pharmacol., in press.

123. Malumbres, M. (2013) Cyclins and Cyclin-dependent kinases. In: Encyclopedia of Systems Biology, (Dubitzky, W., Wolkenhauer, O., Yokota, H. & Cho, K.H., eds.), Springer, Heidelberg, in press. [ISBN 978-1-4419-9864-4]

124. Malumbres, M. (2013) Mitotic kinases. In: Encyclopedia of Systems Biology (Dubitzky, W., Wolkenhauer, O., Yokota, H. & Cho, K.H., eds), Springer, Heidelberg, in press. [ISBN 978-1-4419-9864-4]

125. Malumbres, M. (2013) Control of the cell cycle. In: Abeloff’s Clinical Oncology, 5th edition. (Niederhuber, J.E., Armitage, J.O., Doroshow, J.H., Kastan, M.B., and Tepper, J., eds.) Elsevier, in press.