1 Curriculum Vitae Date Prepared: November 11, 2017 Name: Rosalind Anne Segal Office Address: Departments of Cancer Biology and Pediatric Oncology Dana-Farber Cancer Institute 450 Brookline Avenue, SM1058A Boston, MA 02215 Home Address: 14 Allerton Street Brookline, MA 02445 Work Phone: (617) 632-4737 Work Email: [email protected]Work FAX: (617) 632-4663 Place of Birth: New York, New York Education 1979 A.B. (Summa cum laude) Biochemistry Harvard –Radcliffe, Cambridge, MA 1985 Ph.D. (David JL Luck, MD PhD) Cell Biology Rockefeller University, New York, NY 1986 M.D. Medicine Cornell University Medical College, New York, NY Postdoctoral Training 07/86-16/87 Intern Medicine Beth Israel Hospital, Boston, MA 07/86-16/87 Clinical Fellow Medicine Beth Israel-Deaconess Medical Center, Boston, MA 07/87-6/90 Resident Neurology Harvard Longwood Neurology Program, Boston, MA 07/87-6/92 Clinical Fellow Neurology Children’s Hospital Boston, MA 07/90-12/92 Postdoctoral Fellow Brain and Cognitive Sciences (Ron McKay, PhD) Massachusetts Institute of Technology, Cambridge, MA 01/93-06/95 Postdoctoral Fellow Cell and Molecular Biology (Charles D. Stiles, PhD) Dana-Farber Cancer Institute, Boston, MA Faculty Academic Appointments 07/91-06/95 Instructor Neurology Harvard Medical School 06/95-1/99 Assistant Professor Neurology Harvard Medical School 1/99-10/01 Assistant Professor Neurobiology Harvard Medical School
Transcript
1
Curriculum Vitae Date Prepared: November 11, 2017
Name: Rosalind Anne Segal
Office Address: Departments of Cancer Biology and Pediatric Oncology Dana-Farber Cancer Institute 450 Brookline Avenue, SM1058A Boston, MA 02215
Home Address: 14 Allerton Street Brookline, MA 02445
1986 M.D. Medicine Cornell University Medical College, New York, NY
Postdoctoral Training
07/86-16/87 Intern Medicine Beth Israel Hospital, Boston, MA
07/86-16/87 Clinical Fellow Medicine Beth Israel-Deaconess Medical Center, Boston, MA
07/87-6/90 Resident Neurology Harvard Longwood Neurology Program, Boston, MA
07/87-6/92 Clinical Fellow Neurology Children’s Hospital Boston, MA
07/90-12/92 Postdoctoral Fellow Brain and Cognitive Sciences (Ron McKay, PhD)
Massachusetts Institute of Technology, Cambridge, MA
01/93-06/95 Postdoctoral Fellow Cell and Molecular Biology (Charles D. Stiles, PhD)
Dana-Farber Cancer Institute, Boston, MA
Faculty Academic Appointments
07/91-06/95 Instructor Neurology Harvard Medical School
06/95-1/99 Assistant Professor Neurology Harvard Medical School
1/99-10/01 Assistant Professor Neurobiology Harvard Medical School
2
10/01-10/06 Associate Professor Neurobiology Harvard Medical School
10/06- Professor Neurobiology Harvard Medical School
Appointments at Hospitals/Affiliated Institutions
07/91-12/92 Instructor Neurology Children’s Hospital Boston
07/93-12/94 Instructor Neurology Beth Israel Deaconess
Medical Center
12/93-12/95 Attending in Neurology Neurology Beth Israel Deaconess
Medical Center (East)
12/95-12/98 Senior Attending in
Neurology
Neurology Beth Israel Deaconess
Medical Center (East)
01/99-10/01 Assistant Professor Pediatric Oncology Dana-Farber Cancer
Institute
10/01-10/06 Associate Professor Pediatric Oncology Dana-Farber Cancer
Institute
10/06- Professor Pediatric Oncology Dana-Farber Cancer
Institute
02/09- Professor Cancer Biology Dana-Farber Cancer
Institute
Other Professional Positions
1998-2002 Neurology Consultant, Perini Clinic Dana-Farber Cancer Institute 2006-2013 Consultant Novartis Institutes for Biomedical Research,
Cambridge, MA
Major Administrative Leadership Positions
Local
1995-1997 2002-2006 2003-2008
Co-Director, Brain Tumor Group Chair, Admissions Committee Associate Director, PhD Program in Neuroscience
Beth Israel Deaconess Medical Center Harvard Program in Neuroscience Harvard Medical School
2008-2011
Faculty Director, Life Sciences Academic Ventures
Radcliffe Institute of Advanced Studies, Cambridge, MA
3
2012- 2012-2013
Co-Chair, Dana-Farber Committee on Promotions Co-Chair, Strategic Planning for Research
Dana-Farber Cancer Institute Dana-Farber Cancer Institute
2012- 2014 2014- 2015-
Faculty Council Representative Co-Chair, Faculty Model for Research Director, PhD Program in Neuroscience Co-Chair, Dana-Farber Cancer Biology Dept.
Harvard Medical School Dana-Farber Cancer Institute Harvard University Dana-Farber Cancer Institute
National
2011 Vice-Chair Gordon Conference: Neurotrophic Factors 2013
Chair
Gordon Conference: Neurotrophic Factors
2013
Chair
UCSD Neuroscience Program External Review
2014
Committee Member Stanford Cancer Biology Program External Review
Committee Service Local
1993-1996 Beth Israel Cancer Committee Beth Israel Hospital, Member
1997-2000 M.D.-Ph.D. Admissions Committee Harvard Medical School,
Member 1998- Neuroscience Program Steering
Committee Harvard Medical School, Member
1998- Neuroscience Program Admissions
Committee 1998-2002, 2004 2003-2004
Harvard Medical School, Member Chairperson
1999-2003 Peabody Society – Research Advisor
1999-2001, 2002 2001-2002
Harvard Medical School M.D.-Ph.D. Advisor Senior Research Fellow
2000-2001 M.D.-Ph.D. Clinical Curriculum
Committee Harvard Medical School Member
2001 - Student Advisory Committee,
Neuroscience Program Harvard Medical School
4
2002-2004 Facilities Committee Dana-Farber Cancer Institute 2002-2005 Office of Enrichment Programs Research Harvard Medical School 2005- Faculty Advisor, Women in Neuroscience Harvard Medical School 2006- Barr Grant Review Committee Dana-Farber Cancer Institute
Member 2007-2014 Executive Committee for Research Dana-Farber Cancer Institute
Member 2007-2012 Promotions Committee Dana-Farber Cancer Institute 2008-2009 Freshman Advisor Harvard Medical School 2008-2014
M.D.-Ph.D Advisory Committee (Member)
Harvard Medical School
2009-2012 Promotions and Reappointments
Committee (Member) Harvard Medical School
2010-
Chair Oversight committee, Postdoctoral and Graduate Student Advisory Office
Dana-Farber Cancer Institute
2012-2015 2014- 2014-
Faculty Council Subcommittee of Professors Director, PhD Program in Neuroscience
Harvard Medical School Harvard Medical School Harvard Medical School
Scientific Annual Program Committee NST2 Study Section
American Association for Cancer Research Member
2017- SFN- NTC Chair
Professional Societies
1992- Society for Neuroscience Member 1995- American Academy of Neurology Member 1999
American Association for the Advancement
Member
5
of Science 2007 Society for Glycobiology Member 2011- 2011- 2014-
Association of American Physicians American Association for Cancer Research Society for Developmental Biology
Elected Member Member Member
Grant Review Activities
1995-1998 MDCN6 Study Section NIH Ad hoc reviewer 1995-1997
Christopher Reeve Foundation Review Committee, Ad-Hoc
Christopher Reeve Foundation
1995-1999 National Science Foundation Review
Committee National Science Foundation
1997-1998 Beth Israel – Deaconess Grants Review Beth Israel Deaconess Medical Center 2000- 2004-2007 2010-2012
Barr Grant Review Committee NDBG, Ad hoc reviewer SEPs, Ad hoc reviewer
Dana-Farber Cancer Institute NIH NIH
2012-2014
NIH Director’s Pioneer Grant Reviewer
NIH
2013 2014-
HSCI Seed Grant Review Committee
Member, NST2 Study Section
Harvard Stem Cell Institute NIH
2015- 2017-
Science Advisory Forum Meeting AACR Fellowship Review
Canadian Review Board AACR
Editorial Activities Reviews for: Cell Developmental Cell Nature Medicine Science Nature Molecular and Cellular Biology
6
Journal of Neurobiology Journal of Neuroscience Journal of Cell Biology The Journal of Comparative Neurology Neuron Nature Neuroscience Nature Cell Biology Nature Genetics Endocrinology Genes and Development Proc. Nat. Acad Sci. USA Cancer Research Cancer Cell
Other Editorial Roles
2002-2007
Associate Editor
Journal of Neuroscience
2007-2009 2014-
Reviewing Editor Editorial Board
Journal of Neuroscience Cell Death and Disease
Honors and Prizes
1975 National Merit Scholarship National Merit Scholarship Corporation 1979
Phi Beta Kappa
Harvard College
1979 1979
Summa cum laude, Biochemistry Pre-doctoral Fellowship
Harvard-Radcliffe College National Science Foundation
1980
Pre-doctoral Fellowship
Medical Science Training Program
1990
Post-doctoral Fellowship
Dana Foundation
1990
NINDS Physician Scientist Award (K08)
NINDS
1996
Robert Ebert Clinical Scholar Award
Klingenstein Foundation
1998
Claudia Adams Barr Investigator
Barr Foundation
2001
Pediatric Brain Tumor Foundation Award
Pediatric Brain Tumor Foundation of the United States
2001
McDonnell Foundation Award
McDonnell Foundation
2006
NIH Director’s Pioneer Award
NIH
7
2009
Ted Williams Senior Investigator
Dana-Farber Cancer Institute
2010 2011 2015 2016
Eureka Grant Award American Association of Physicians Casty Family Mentoring Award Edward J. Benz, Jr. Chair
NIH Elected to membership Dana-Farber Cancer Institute Dana-Farber Cancer Institute
Report of Funded and Unfunded Projects Funding Information Past 1991-1995 Neural Stem Cell Lines PI NIH/NINDS K08 The major goal was to generate and characterize retinal cell lines. 1996-2004 Retrograde Signal Transduction by Neurotrophins NIH/R01 NS035148 PI The major goals of this project were to learn how Trks function as retrograde signal
carriers; how P-Trk signal arriving at the nerve cell body is converted to a nuclear signal; and to test the hypothesis that PI3 kinases are required for retrograde signaling through long axons.
2001-2003 Genetics Modifiers of Medulloblastoma James S. McDonnell Foundation, Research Award PI The goal of this project was to find out how proteoglycan molecules work with sonic
hedgehog to make cells divide. 2002-2003 Loss of Coordinate Regulation of Migration and Proliferation in Medulloblastoma Pediatric Brain Tumor Foundation of the United States PI The major goal of this project was to define the relationship between the initiation of
migration and cessation of proliferation during neuronal development.
2004-2005 Therapeutic Use of CXCR4 Antagonists in Glioblastoma Accelerate Brain Cancer Cure (ABC2), Research Grant PI The major goals of this project were to evaluate combinations of CXCR4 inhibition with
conventional therapies and to elucidate the role of PTEN on CXCR4 expression and
8
function.
2004-2006 Trafficking of Neurotrophic Receptors in ALS NIH/R21 NS049381 PI The major goals of this R21 were: 1) to test the hypothesis that there is a loss of long range
neurotrophin signaling in human ALS specimens and in SODI transgenic animals; 2) to determine whether Alsin, the product of ALS2 gene at 2q33-35, is required for vesicular trafficking of Trk receptors and for retrograde signaling by neurotrophins; 3) to identify the nature of the dynein motors that transport long range survival signals, and whether these are assembled in response to neurotrophin stimulation.
2006-2007 The Role of Alsin in Motor Neuron Survival Muscular Dystrophy Association, Research Grant PI The major goals of this project were to determine whether Aslin is required for vesicular
trafficking and for retrograde signaling by target-derived neurotrophic factors; to determine which of the GEF domains of Alsin are important for function in motor neurons.
2006-2008 Symmetric and Asymmetric Proliferation of Glioma Stem Cells Harvard Stem Cell Institute, Pilot Research Grant PI The major goals of this project were identify the critical targets of cyclopamine and
Gleevec in glioma treatment, and to test this combination of therapies in animal models of intracranial glioma; and to determine the mechanism of the synergy of these two compounds.
2006-2011
NIH Director’s Pioneer Award
NIH/DP1 OD000839 PI ($2,500,000) The broad goals for this award are to determine whether proteoglycan structure can specify
a mitogenic niche, and to compare the nature of oncogenic and developmental stem cell niches.
2007-2012 Sonic Hedgehog Pathway in Brain Tumors Dana-Farber/Novartis Drug Discovery Program/060018 PI PI ($525,000 in period of 2011-2012) The broad goal is to determine whether combination therapy is a viable approach for
treating high grade gliomas, and to identify subclass(es) of these tumors that are most likely to respond. Subsequently to 1) Identify genes that, when mutated, can cause therapeutic resistance to Smo inhibitors; and 2) Test the hypothesis that kinases and phosphatases that impinge on the Shh pathway provide effective targets to prevent therapeutic resistance to Smo inhibitors.
1998-2012 Cell-Cell Interactions in Cerebellar Development NIH/NINDS /R01 NS037757 PI ($500,000)
The specific aims of this research are to: 1) Determine the mechanism by which BDNF promotes granule cell migration; 2) Test the hypothesis that a gradient of BDNF causes redistribution of TrkB receptors to amplify the gradient and provide a direction for
9
chemotaxis; 3) Test the hypothesis that SDF-1alpha functions as a spatially restricted competence factor that limits Shh-induced proliferation to the EGL.
2010-2015
New approaches to local translation: spaceSTAMP of proteins synthesized in axons NIH R01 MH091662 PI The goal of this proposal is to develop the spaceSTAMP approach and use it to ask: Is there regulated local translation in axons? Are such locally translated proteins functionally important? Are locally translated proteins restricted to the axonal compartment, or do they facilitate communication between axonal terminals and remote portions of the neuronal cell body?
2011-2013 Changes in hedgehog signaling and cell division in aging and diseases Emerald Foundation PI ($150,000/year) The proposed research will identify changes in the hedgehog (Hh) signaling network and resultant changes in neural stem cells during aging to discover how these can be reversed.
2011-2014
Tumor Cell Biology Training Program NIH/NCI T32 CA009361 PI: ($500,000/year) Our broad goal is to teach young scientists at the pre- and post-doctoral levels how to apply emerging technology in genomics and proteomics to fundamental problems in cell division, cell differentiation or cell death that underlie human neoplastic disease. *This award is still active, under Dr. Nathanael Gray, PI
2011-2017 Therapeutic Opportunities for Pediatric Astrocytoma NIH/NCI /1P01 CA142536-01A1 Program Director, Project PI (NCE) The long-term goal of this program is to improve the standard of care for pediatric
astrocytomas - the most common brain cancers in children. Towards this end, we will improve our understanding of astrocytoma biology and develop new diagnostic, prognostic and therapeutic tools for these tumors. Three major projects, each co-directed by a basic scientist and a physician-scientist, will provide new insights from these studies so that they can be rapidly translated into novel clinical treatments.
2011-2016 Spatial Considerations in Neuronal Survival Signals NIH/NINDS R01 NS050674
PI (NCE) The specific aims of this project are to: 1) To determine the mechanisms responsible for
induction of retrograde response genes by target-derived neurotrophins, using both motor and sensory neurons grown in compartmented cultures; 2) To determine the functions of retrograde response genes in developing and mature neurons; 3) To test the hypothesis that mutations in dynein that cause ALS do so by interfering with induction of bclw and other retrograde response genes, and that expression of these genes may protect motor neurons from progressive degeneration.
2013-2015 Rescuing axons from chemo-induced peripheral neuropathy Claudia Adams Barr Award
10
PI ($150,000/year) The specific aims are: 1) To develop models for studying the mechanism of CIPN; 2) To
determine whether chemotherapeutic agents impinge on Bclw regulation or function, and; 3) To determine whether Bclw expression can prevent CIPN.
2013-2016
Pediatric Low Grade Astrocytoma Foundation
Co-Investigator ($140,000/year) The major goal of my project is to generate mouse models of Pilocytic Astrocytoma 2014-2016 Therapies for SHH-subtype medulloblastoma
Alex’s Lemonade Stand Innovator Award Principal Investigator ($125,000/year) This proposal aims to identify mechanisms of resistnance to Smo inhibitors, and to foster
novel therapies for SHHsubtype MBs that do no respond to Smo inhibitors. 2014-2016
Neurotrophin regulation of axonal translation Harvard/MIT Joint Research PI The specific aims of this proposal are to: 1) Test the hypothesis that neurotrophin stimulation of developing sensory neurons regulates ribosome biogenesis and/or axonal localization; 2) Identify the axonal translatome of dorsal root ganglion neurons in vivo.
Current 2014-2018 2016-2021 2016-2018
PhD Training in Neuroscience NIH/NIHMS T32 MH020017 PI ($607,964) The goals of this program are to: 1) Organize within a single training facility the neuroscientists at Harvard Medical School, its affililiated hospitals, and Harvard College; 2) Traini research scientists and teachers who are interested in mental health diseases of the nervous system and fundamental mechanisms of the brain. (PQ9) The role of Bclw (bcl212) in preventing chemotherapy induced neuropathy NIH R01 CA205255 PI ($343,170/year) The proposed studies will elucidate the mechanisms whereby paclitaxel and other chemotherapies affect Bclw expression, and how Bclw prevents chemotherapy induced axonal degeneration. Bridge Project Funds-MIT-DFCI PI (200,00/year)
Report of Local Teaching and Training Teaching of Students in Courses 1992-1994 Cell and Developmental Biology Harvard Medical School 15 Graduate Students 2-hr sessions per wk for 2 wks
11
1997-2006
Neurobiology 207 Developmental Neurobiology 20 Graduate Students
Harvard Medical School 4-hr sessions per wk for 4-6 wks
1998
Introductory Neuroscience
Harvard Medical School
100 Medical Students 6-hr sessions per wk for 1 wk 2007-2016
HST 130 Neuroscience; Block Head
Harvard Medical School
40 Medical Students, 15 Graduate Students 9-hr sessions per wk for 4 wks 2011
CB 399: Hedgehog Signaling in Cancer
Harvard Medical School
15 Graduate Students 6-hr sessions per wk for 1 wk 2012
Experimental Design
Harvard Medical School
2013-2015
6 Graduate Students CB211 Cancer Biology 31 Graduate Students
5 3-hr sessions per wk for 1 wk Harvard Medical School 2, 2-hour sessions
2014 2015-2017
Stem Cell & Regenerative Biology Harvard University One 3-hour session
Formally Supervised Trainees
Graduate Students
1994-1998 Phillip Schwartz, PhD/ CEO Entera Bio, Israel 1995-2001
Fiona Watson, PhD/ Assistant Professor of Biology, Washington and Lee
1996-1997
Richard Levy, MD/ Professor of Ophthalmology, Weill Cornell Medical College
1996-2000
Paul Borghesani, MD, PhD/ Assistant Professor, University of Washington, Seattle
1998-2002
Alexandre Carter, MD, PhD/ Assistant Professor of Neurology, WUSTL
1998-2003
Joshua Rubin, MD, PhD/ Associate Professor of Pediatrics, WUSTL
1998-2004
Heather Heerssen, PhD/ Senior Medical Writer, Complete Healthcare Communications
1999-2000
Yvonne Yannoni, PhD/ Staff Scientist, Genetics Institute
2000-2007 2000-
Yoojin Choi, BS/ Associate Professor at North Park University, Chicago, IL Maria Pazyra-Murphy, PhD/Lab Manager
12
2001-2003 Marimelia Porcionatto, PhD/ Professor of Molecular Biology, Federal University of Sao
Paulo 2001-2005
Christoph Karch, MD/ Resident, Neurology, Tufts University
2001-2005
Jennifer Chan, MD/ Assistant Professor, Departments of Pathology & Laboratory Medicine, Clinical Neurosciences, and Oncology, University of Calgary
2003-2006
Aymeric Hans, PhD/ Head of Virology Team, AFSSA-LERPE-Dozule Pathology and Disease Research Lab, France
Adriana Eisner, PhD/ Associate Consultant, McKinsey & Company
2007-2016
Katharina Cosker, PhD/ University College London
2007-2012
Tatyana Ponomaryov, PhD/ Research Scientist, University of Birmingham, Birmingham, UK
2007-2017
Xuesong Zhao, PhD/ Research Fellow
2008-2010
Kristina Rehm, PhD/ Senior Medical Writer, Vertex Pharmaceuticals
2008-2012
Mariella Gruber-Filbin, MD, PhD/ Clinical Fellow, Department of Pediatrics, Children’s Hospital Boston
2009-2015
Sara Fenstermacher, PhD/ Post-doctoral Fellow, Jessel laboratory, Columbia University
2011-2016
Sarah Pease, PhD/ Post-doctoral Fellow, Chan Laboratory, UCSF
2011-2012
Marie-Lyn Hecht, PhD/ Associate, Management Consulting, Booz & Company GmbH
2011-2016
Ekaterina Pak, PhD/ Graduate Student
2012 -
Emily Chadwick, BS/Research Technician
13
2014-2015
Oded Behar, Ph.D./Visiting Scientist
2014 - 2015
Meijia Gu, Ph.D./Research Fellow
2014 -
Ethan Mackenzie, MD Research Fellow
2014 -
Ozge Tasdemir-Yilmaz, Research Fellow
2015 -2016
Kenley Preval, BA/MD-PhD student, University of Massachusetts.
Supervised Undergraduate Theses
Maricel Pilapil
Yicheng Cheng Meghan Galligan Lauren Schumacher Samuel Cohen Laura Persson Eugene Vaios Summer Undergraduates Samuel Cohen Jarom Chung Eshaan Rao Gifty Adae Phillip Stephens Gabrielle Price
Preliminary Exam Committees (last two years only are listed) Ryoji Amamoto Fongching Chau Michael Coulter Costadin Petrov Cem Sengel Xiaoji Wu Hugo Ramirez Sonia Kim
Dissertation Advisory Committees (last two years only are listed) Lauren Barclay Xuyu Cai Kevin Chau Michael Coulter Gustavo German
14
Erica Gornstein Divya Jayaraman Mark McClintock Allison Nishitani Cole Peters Heather Rice Illana Stanley Mary Wertz Jennifer Yeh
Dissertation Defense Committees Victoria Abraira Chester Chamberlain Masha Gelfand Corey Harwell (MIT) Misao Higashi Nina Hunter Lyle Lopez Heather Mason Claire McKellar Lauren Marotta Maurice Perrinjacquet (Karolinska Institute, Sweden) Heather Rieff Geoffrey Tanner Mary Wertz Report of Regional, National and International Invited Teaching and Presentations
Invited Presentations and Courses
Regional 1999 Neurotrophins in Cerebellar Development and Disease/ Lecture Brandeis University, Waltham, MA 2000 Retrograde Signaling by Neurotrophins/ Lecture Woods Hole Marine Biology Laboratory, MA 2000 Retrograde Signaling by Neurotrophins/ Lecture University of Massachusetts Medical Center, MA 2001 Retrograde Signaling by Neurotrophins/ Lecture Boston University Medical School, Department of Pathology, MA 2001 Retrograde Signaling by Neurotrophins/ Lecture Massachusetts Institute of Technology, Brain and Cognitive Sciences, Cambridge, MA 2003 A Developmental Approach to Brain Tumor Biology/ Lecture Shriver Institute, University of Massachusetts Medical School, Waltham, MA 2008 Neuro-Oncology Conference/ Lecture
15
Brigham and Women’s Hospital, Boston, MA 2009 Invited Talk Dana-Farber/Novartis Annual Joint Scientific Retreat, Lake Tahoe, Incline Village, NV 2010 M.R. Bauer Colloquium Series, “The Neurobiology of Disease”/ Talk Volen Center for Complex Systems, Brandeis University, Waltham, MA Keynote Talk 2010 Science Presentation/ Talk Wellesley College, Wellesley, MA 2010 Resistance to Smoothened Inhibitors/ Invited Talk Dana-Farber/Novartis Annual Joint Scientific Retreat, Chateau Elan, Braselton, GA 2011 Targeting Renewal and Expansion in Glioblastoma: A one-Two Punch/ Invited Talk Children’s Hospital Boston Seminar Series, Boston, MA 2011 Preparing Faculty to Teach the Neurobiology of Brain Dysfunction/ Invited Presentation Marine Biological Laboratory, Woods Hole, MA 2011 Harvard MD-PhD Retreat, Eva Neer Memorial Lecture
Cape Cod, MA National 1995 Neurotrophic Factors/ Lecture American Academy of Neurology 1996 Neuronal Plasticity and Repair/ Lecture Asilomar Conference, Monterey, CA 1997 Neurodevelopment – Bench to Bedside/ Lecture American Academy of Neurology 1997 Retrograde signaling by NGF in vivo/ Lecture Gordon Research Conference on Neurotrophins (Neurotrophic Factors), Newport, RI 1997 Neurotrophins in Cerebellar Development and Disease/ Lecture University of Cincinnati, OH 1998 Neurotrophins in Cerebellar Development and Disease/ Lecture Uniformed Services University of the Health Sciences, Bethesda, MD 1998 Neurodevelopment – Bench to Bedside/ Lecture American Academy of Neurology 1998 Neurotrophins in Cerebellar Development and Disease/ Lecture Case Western Reserve University, Cleveland, OH 1999 Neurodevelopment – Bench to Bedside/ Lecture American Academy of Neurology 1999 Neurotrophins in Cerebellar Development and Disease/ Lecture Johns Hopkins University Medical School, Baltimore, MD 2000 Retrograde Signaling of Neurotrophins/ Lecture Mount Sinai Medical Center, New York, NY 2000 Signal transduction through axons- the challenge of distance/ Talk Gordon Research Conference on Cell Biology of the Neuron, Plymouth, NH 2000 Neurotrophic Factors/ Talk American Society for Neurochemistry Annual Meeting 2001 Protein Kinases and Phosphatases/ Lecture FASEB Meeting 2001 Retrograde Signaling by Neurotrophins/ Lecture
16
Columbia University Medical School, Department of Pathology, Ithaca, NY 2001 Retrograde Signaling by Neurotrophins: The challenge of distance/ Talk Gordon Research Conference on Neurotrophins (Neurotrophic Factors), Newport, RI 2002 Erk5 Mediates Retrograde Survival Signaling/ Lecture University of Rochester Medical School, Rochester, NY 2002 Erk5 Mediates Retrograde Survival Signaling/ Lecture University of North Carolina at Chapel Hill 2002 Erk5 Mediates Retrograde Survival Signaling/ Lecture Duke University, Department of Pharmacology, Durham, NC 2002 Erk5 Mediates Retrograde Survival Signaling/ Talk NIH Director’s Seminar 2002 Erk5 Mediates Retrograde Survival Signaling/ Talk Society For Neuroscience Annual Meeting, Orlando, FL 2002 Erk5 Mediates Retrograde Survival Signaling/ Lecture University of Iowa, Iowa City, IA 2002 SDF-1α in cerebellar development and disease/ Talk Gordon Research Conference on Chemotactic Cytokines, South Hadley, MA 2002 Erk5 Mediates Retrograde Survival Signaling/ Lecture University of Colorado, Denver, Department of Pharmacology, Denver, CO 2002 Retrograde Signaling by Neurotrophins/ Lecture University of Washington, Department of Pharmacology 2003 Limiting Proliferation in Time and Space: Sonic hedgehog modifiers/ Lecture McDonnell Foundation 21st Century Science Initiative Meeting, St. Louis, MO 2003 Retrograde Neurotrophin Signaling/ Lecture UCLA Brain Research Seminars, Los Angeles, CA 2003 Retrograde Neurotrophin Signaling/ Lecture Georgetown University, Department of Neuroscience, Washington, DC 2004 Retrograde Neurotrophin Signaling/ Lecture St. Jude’s Hospital, Memphis, TN 2005 TrkB provides direction for migrating precursor cells/ Talk Gordon Research Conference on Neurotrophic Factors, Newport, RI 2005 Invited Lecture Department of Neuroscience, University of Pennsylvania 2005 Invited Lecture Department of Cell Biology, University of Virginia 2005 Invited Lecture Department of Cell Biology, Emory University 2006 Development from Stem Cell to Synapse/ Lecture Society For Neuroscience – Symposium 2007 Invited Lecture Department of Pharmacology, Duke University, Durham, NC 2007 Proteoglycan Interactions with Sonic Hedgehog Are Selectively Required for Mitogenic
Responses/ Lecture Third Annual NIH Director’s Pioneer Award Symposium, Bethesda, MD 2008 Invited Lecture Vollum Institute, Oregon Health & Science University, Portland, OR 2009
Sonic Hedgehog-Proteoglycan Interactions Promote Proliferation of Neural Precursors/ Lecture
Stem Cell Seminar, Columbia University Medical Center, New York, NY
17
2009 BDNF, Numb and Polarized Migration of Neural Precursors/ Lecture Mahoney Institute of Neurological Sciences, University of Pennsylvania 2009 Neurotrophin actions in developing cerebellum/ Talk Gordon Research Conference on Neurotrophic Factors, Newport, RI 2009 Proteoglycans Specify a Mitogenic Response to Sonic Hedgehog/ Lecture Neuro-oncology Research Group Seminar Series, WUSTL, St. Louis, MO 2010 Mitogenic Niches in the Brain: Sonic Hedgehog and Proteoglycans/ Lecture Rutgers University Colloquium Seminar Series, New Jersey 2010 Activation of axonal Trk receptors induces retrograde response genes critical for axonal
survival/ Lecture FASEB Summer Research Conferences – Receptor Tyrosine Kinases: Biology and Cancer,
Carefree, AZ 2010 Sonic Hedgehog Development and Disease/ Invited Talk Mount Sinai School of Medicine, Endocrinology Grand Rounds, New York, NY 2010 There and back again: Neurotrophic-induced retrograde response genes promote axonal
viability/ Invited Keynote Lecture Eight Annual Meeting of the Front Range Neuroscience Group, Fort Collins, CO 2011 Sonic Hedgehog and Proteoglycans in neural stem cell proliferation/ Invited Talk Seminar: Division of Neurobiology & H. Wills Neuroscience Institute, UC Berkeley, CA 2011 There and back again: Neurotrophic-induced retrograde response genes promote axonal
viability/ Invited Talk Department of Neurosciences Seminar, Case Western Reserve University, Cleveland, OH 2011 Retrograde response genes and neuronal survival/ Invited Lecture ASBMB Annual Meeting, Washington, DC 2011 Mitogenic Niches in the Brain: Sonic Hedgehog and Proteoglycans/ Invited Talk
Leon Levy and Shelby White Center for Mind, Brain and Behavior Neuroscience Seminar Series, The Rockefeller University, New York, NY
2011 Modulators of Shh Signaling: Novel Approaches/ Invited Presentation Seventh Annual NIH Director’s Pioneer Award Symposium, Bethesda, MD 2011 Common Themes in Normal and Neoplastic Brain Development/ Invited Lecture American Neurological Association 136th Annual Meeting – Symposium: The
Neurobiology of Neuro-Oncology, San Diego, CA 2011 There and Back Again: Neurotrophin Regulation of the Retrograde Response Gene bcl-w/
Invited Presentation Society for Neuroscience Annual Meeting – Symposium: From Synapse to Nucleus and
Back Again – Communicating Over Distance Within Neurons, Washington, DC Modulators of Shh Signaling: Novel Approaches/ Invited Talk 2012 Combinatorial targeting of PI3 kinase and Shh signaling in brain tumor / Invited Talk
Annual Meeting of the American Association for Cancer Research, Chicago, IL 2012 From Here to There: Mechanisms of BDNF-induced Cell Migration / Invited Talk
Fred Hutchinson Cancer Research Center, Seattle, WA 2012 Coordinate Activation of the Shh and PI3K Signaling Pathways in Glial Progenitor Cells:
An Opportunity for Brain Penetrant Targeted Therapeutics / Invited Talk BTC Retreat, Memorial Sloan-Kettering Cancer Center, New York City, NY
2012 There and Back Again: Neurotrophin Regulation of Axonal Viability / Invited Talk Burke Medical Research Institute, White Plains, NY
2013 Neurotrophin Regulation of Bclw Transcription and Translation/Invited Talk University of Pennsylvania/Childrens Hospital of Philadelphia
2014 Axon Survival: City University of New York 2014 Keynote Lecture, Tri-Institutional MD-PhD Program Retreat
18
2014 Keynote Lecture, GRC on Developmental Neurobiology 2014 Tufts University, MD-PhD program dinner speaker 2014 Memorial Sloan Kettering Brain Tumor Seminar Program 2014 NIH:NINDS Seminar series International 2003 Retrograde Neurotrophin Signaling/ Talk Killam Seminar, Montreal Neurological Institute, Canada 2004 Spatial view of growth factor signaling/ Talk Gordon Research Conference on Molecular & Cellular Neurobiology, Hong Kong, China 2004 Molecular & Cellular Neurobiology, Riken Neuroscience Institute, Tokyo, Japan 2009 BDNF and Chemotaxis of Neural Precursors/ Lecture EMBO Spatial 2009 – Overcoming Distance in Signaling Networks, Israel 2010 Molecular Neuroscience Forum/ Lecture Weizmann Institute of Science, Rehovot, Israel 2010 Glycomics of the Mitogenic Niches in the Brain/ Talk Armenise Meeting; Frascati, Italy 2010 Invited Talk Department of Neuroscience, Karolinska Institute, Stockholm, Sweden 2012 There and Back Again: Neutrophin Regulation of Retrograde Response Genes / Invited Talk
NGF 2012 Meeting, Wuerzburg, Germany 2014 Invited Lecture, EMBO Conference on Neuronal Remodeling, Ein Gedi, Israel 2014 Invited Lecture, Japanese Society for Neuroscience, Yokohama, Japan Report of Clinical Activities and Innovations
1995-1997 Founding co-Director of the Brain Tumor Program BIDMC
may mediate the Ca2+-dependent photophobic response. J Cell Biol. 1985;101(5 Pt 1):1702-12. PMCID: PMC2113956
6. Segal RA, Chapman C, Barlow J. Monozygotic twins with seizures. Shared characteristics. Arch Neurol. 1991;48(10):1041-5.
7. Segal RA, Takahashi H, McKay RD. Changes in neurotrophin responsiveness during the development of cerebellar granule neurons. Neuron. 1992;9(6):1041-52.
8. Segal RA, Goumnerova LC, Kwon YK, Stiles CD, Pomeroy SL. Expression of the neurotrophin receptor TrkC is linked to a favorable outcome in medulloblastoma. Proc Natl Acad Sci U S A. 1994;91(26):12867-71. PMCID: PMC45541
9. Segal RA, Pomeroy SL, Stiles CD. Axonal growth and fasciculation linked to differential expression of BDNF and NT3 receptors in developing cerebellar granule cells. J Neurosci.
20
1995;15(7 Pt 1):4970-81. 10. Segal RA, Bhattacharyya A, Rua LA, Alberta JA, Stephens RM, Kaplan DR, Stiles CD.
Differential utilization of Trk autophosphorylation sites. J Biol Chem. 1996;271(33):20175-81. 11. Nachmanoff DB, Segal RA, Dawson DM, Brown RB, De Girolami U. Hereditary ataxia with
Greenberg ME. Regulation of neuronal survival by the serine-threonine protein kinase Akt. Science. 1997;275(5300):661-5.
13. Cabelli RJ, Shelton DL, Segal RA, Shatz CJ. Blockade of endogenous ligands of trkB inhibits formation of ocular dominance columns. Neuron. 1997;19(1):63-76.
14. Schwartz PM, Borghesani PR, Levy RL, Pomeroy SL, Segal RA. Abnormal cerebellar development and foliation in BDNF-/- mice reveals a role for neurotrophins in CNS patterning. Neuron. 1997;19(2):269-81.
15. Bhattacharyya A, Watson FL, Bradlee TA, Pomeroy SL, Stiles CD, Segal RA. Trk receptors function as rapid retrograde signal carriers in the adult nervous system. J Neurosci. 1997;17(18):7007-16.
16. Schwartz PM, Levy RL, Borghesani PR, Segal RA. Cerebellar pathology in BDNF -/- mice: the classic view of neurotrophins is changing. Mol Psychiatry. 1998;3(2):116-20.
17. Ma Q, Jones D, Borghesani PR, Segal RA, Nagasawa T, Kishimoto T, Bronson RT, Springer TA. Impaired B-lymphopoiesis, myelopoiesis, and derailed cerebellar neuron migration in CXCR4- and SDF-1-deficient mice. Proc Natl Acad Sci U S A. 1998;95:9448-53. PMCID: PMC21358
18. Kim JY, Sutton ME, Lu DJ, Cho TA, Goumnerova LC, Goritchenko L, Kaufman JR, Lam KK, Billet AL, Tarbell NJ, Wu J, Allen JC, Stiles CD, Segal RA, Pomeroy SL. Activation of neurotrophin-3 receptor TrkC induces apoptosis in medulloblastomas. Cancer Res. 1999;59(3):711-9.
20. Watson FL, Heerssen HM, Moheban DB, Lin MZ, Sauvageot CM, Bhattacharyya A, Pomeroy SL, Segal RA. Rapid nuclear responses to target-derived neurotrophins require retrograde transport of ligand-receptor complex. J Neurosci. 1999;19(18):7889-900.
21. Borghesani PR, Alt FW, Bottaro A, Davidson L, Aksoy S, Rathbun GA, Roberts TM, Swat W, Segal RA, Gu Y. Abnormal development of Purkinje cells and lymphocytes in Atm mutant mice. Proc Natl Acad Sci U S A. 2000;97(7):3336-41. PMCID: PMC16240
22. O’Brien SP, Seipel K, Medley QG, Bronson R, Segal R, Streuli M. Skeletal muscle deformity and neuronal disorder in Trio exchange factor-deficient mouse embryos. Proc Natl Acad Sci U S A. 2000;97(22):12074-8. PMCID: PMC17296
23. Zhang Y, Moheban DB, Conway BR, Bhattacharyya A, Segal RA. Cell surface Trk receptors mediate NGF-induced survival while internalized receptors regulate NGF-induced differentiation. J Neurosci. 2000;20(15):5671-8.
imaging demonstrates dynein-based vesicular transport of activated Trk receptors. J Neurobiol. 2002;51(4):302-12.
31. Kim JY, Koralnik IJ, LeFave M, Segal RA, Pfister LA, Pomeroy SL. Medulloblastomas and primitive neuroectodermal tumors rarely contain polyomavirus DNA sequences. Neuro Oncol. 2002;4(3):165-70. PMCID: PMC1920639
32. Wang KC, Kim JA, Sivasankaran R, Segal R, He Z. P75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG, and OMgp. Nature. 2002;420(6911):74-78.
33. Carter AR, Berry EM, Segal RA. Regional expression of p75NTR contributes to neurotrophin regulation of cerebellar patterning. Mol Cell Neurosci. 2003;22(1):1-13.
34. Kim JY, Nelson AL, Algon SA, Graves O, Sturla LM, Goumnerova LC, Rowitch DH, Segal RA, Pomeroy SL. Medulloblastoma tumorigenesis diverges from cerebellar granule cell differentiation in patched heterozygous mice. Dev Biol. 2003;263(1):50-66.
35. Rubin JB, Kung AL, Klein RS, Chan JA, Sun Y, Schmidt K, Kieran MW, Luster AD, Segal RA. A small-molecule antagonist of CXCR4 inhibits intracranial growth of primary brain tumors. Proc Natl Acad Sci U S A. 2003;100(23):13513-8. PMCID: PMC263845
36. Heerssen HM, Pazyra MF, Segal RA. Dynein motors transport activated Trks to promote survival of target-dependent neurons. Nat Neurosci. 2004;7(6):596-604.
37. Choi Y, Borghesani PR, Chan JA, Segal RA. Migration from a mitogenic niche promotes cell-cycle exit. J Neurosci. 2005;25(45):10437-45.
38. Redjal N, Chan JA, Segal RA, Kung AL. CXCR4 inhibition synergizes with cytotoxic chemotherapy in gliomas. Clin Cancer Res. 2006;12(22):6765-71.
39. Zhou P, Porcionatto M, Pilapil M, Chen Y, Choi Y, Tolias KF, Bikoff JB, Hong EJ, Greenberg ME, Segal RA. Polarized signaling endosomes coordinate BDNF-induced chemotaxis of cerebellar precursors. Neuron. 2007;55(1):53-68. PMCID: PMC2661852
40. Ha J, Lo KW, Myers KR, Carr TM, Humsi MK, Rasoul BA, Segal RA, Pfister KK. A neuron-specific cytoplasmic dynein isoform preferentially transports TrkB signaling endosomes. J Cell Biol. 2008;181(6):1027-39. PMCID: PMC2426944
41. Chan JA, Balasubramanian S, Witt RM, Nazemi KJ, Choi Y, Pazyra-Murphy MF, Walsh CO, Thompson M, Segal RA. Proteoglycan interactions with Sonic Hedgehog specify mitogenic responses. Nat Neurosci. 2009;12(4):409-17. PMCID: PMC2676236
42. Arimura N, Kimura T, Nakamuta S, Taya S, Funahashi Y, Hattori A, Shimada A, Ménager C, Kawabata S, Fujii K, Iwamatsu A, Segal RA, Fukuda M, Kaibuchi K. Anterograde transport of TrkB in axons is mediated by direct interaction with Slp1 and Rab27. Dev Cell. 2009;16(5):675-86.
43. Pazyra-Murphy MF, Hans A, Courchesne SL, Karch C, Cosker KE, Heerssen HM, Watson FL, Kim T, Greenberg ME, Segal RA. A retrograde neuronal survival response: target-derived neurotrophins regulate MEF2D and bcl-w. J Neurosci. 2009;29:6700-9. PMCID: PMC2709981
Loss of Bcl-w. 2011. J Neurosci. 2011;31(5):1624-34. PMCID: PMC3074348 45. Courchesne SL, Pazyra-Murphy MF, Segal RA. Neuromuscular junction defects in mice with
mutation of dynein heavy chain 1. PLoS One. 2011;6(2):e16753. PMCID: PMC3035627 46. Zhou PC, Alfaro J, Chang EH, Zhao X, Porcionatto M, Segal RA. Numb links extracellular cues
to intracellular polarity machinery to promote chemotaxis. Dev Cell. 2011;20(5):610-22. PMCID: PMC3103748
47. Fainzilber M, Budnik V, Segal RA, Kreutz MR. From synapse to nucleus and back again- communication over distance within neurons. J Neurosci. 2011 Nov 9;31(45):16045-8.
48. Cosker KE, Pazyra-Murphy MF, Fenstermacher SJ, Segal RA. Target-derived neurotrophins coordinate transcription and transport of bclw to prevent axonal degeneration. J Neurosci. 2013 33(12):5195-207.
49. Witt RM, Hecht ML, Pazyra-Murphy MF, Cohen SM, Noti C, van Kuppevelt TH, Fuller, M, Chan JA, Hopwood JJ, Seeberger PH, Segal, RA. Heparan Sulfate Proteoglycans Containing a Glypican 5 Core and 2-O-Sulfo-iduronic Acid Function as Sonic Hedgehog Co-receptors to Promote Proliferation. J. Biol Chem. 2013 Sep 6;288(36):26275-88. Doi: 10.1074/jbc.M112.438937. Epub 2013 July 18. PMID: 2387465
50. Gruber-Filbin M, Dabral SK, Ramkissoon S, Kung AL, Pak E, Chung J, Theisen MA, Sun Y, Franchetti Y, Sun Y, Shulman DS, Redjal N, Tabak B, Beroukhim R, Wang Q, Zhao J, Buonamici MDS, Ligon KL, Kelleher JF, Segal RA. Coordinate activation of Shh and PI3 kinase signaling pathways in PTEN-deficient glioblastoma presents new opportunities for targeted therapy. Nat. Med. 2013 Nov; 19(11):1518-23. Doi:10.1038/nm.3328. Epub 2013 Sep 29. PubMed PMID: 24076665.
52. Eisner A, Pazyra-Murphy MF, Durresi E, Zhou P, Zhao X, Chadwick EC, Xu PX, Hillman RT, Scott MP, Greenberg ME, Segal RA. The Eya1 Phosphatase Promotes Shh Signaling during Hindbrain Development and Oncogenesis. Dev Cell. 2015 Apr 6;33(1):22-35. doi: 10.1016/j.devcel.2015.01.033. Epub 2015 Mar 26.
53. Zhao X, Ponomaryov T, Ornell KJ, Zhou P, Dabral SK, Pak E, Li W, Atwood SX, Whitson RJ, Chang AL, Li J, Oro AE, Chan JA, Kelleher JF, Segal RA. RAS/MAPK activation drives resistance to Smo inhibition, metastasis and tumor evolution in Shh pathway-dependent tumors. Cancer Res. 2015 Jun 30. pii: Cancer Research . PMID: 2613065
54. Zhou P, Erfani S, Liu Z, Jia C, Chen Y, Xu B, Deng X, Alfáro JE, Chen L, Napier D, Lu M, Huang JA, Liu C, Thibault O, Segal R, Zhou BP, Kyprianou N, Horbinski C, Yang XH. Oncotarget. 2015 Oct 6;6(30):29675-93. doi: 10.18632/oncotarget.4896 PMID:26377974
55. Balastik M, Zhou XZ, Alberich-Jorda M, Weissova R, Žiak J, Pazyra-Murphy MF, Cosker KE, Machonova O, Kozmikova I, Chen CH, Pastorino L, Asara JM, Cole A, Sutherland C, Segal RA, Lu KP. Prolyl Isomerase Pin1 regulates Axon Guidance by Stabilizing Crmp2A selectively in distal axons. Cell Rep. 2015 Oct 27;13(4):812-28. doi: 10.1016/j.celrep.2015.09.026. Epub 2015 Oct 17.PMID: 26489457
56. Chadwick EJ, Yang DP, Filbin MG, Mazzola E, Sun Y, Behar O, Pazyra-Murphy MF, Goumnerova L, Ligon KL, Stiles CD, Segal RA. J Vis Exp. 2015 Nov 7;(105). doi: 10.3791/53304. PMID: 26575352
57. Bergthold G, Bandopadhayay P, Hoshida Y, Ramkissoon S, Ramkissoon L, Rich B, Maire CL, Paolella BR, Schumacher SE, Tabak B, Ferrer-Luna R, Ozek M, Sav A, Santagata S, Wen PY, Goumnerova LC, Ligon AH, Stiles C, Segal R, Golub T, Grill J, Ligon KL, Chan JA, Kieran MW, Beroukhim R. Neuro Oncol. 2015 Nov;17(11):1486-96. doi: 10.1093/neuonc/nov045. Epub
23
2015 Mar 29. PMID: 25825052 58. Cosker KE, Fenstermacher SJ, Pazyra-Murphy MF, Elliot HL, Segal RA. The RNA-binding
protein SFPQ orchestrates an RNA regulon to promote axon viability. Nature Neuroscience 2016. 59. Jing Ni, Shaozhen Xie, Shakti H Ramkissoon, Victor Luu, Yu Sun, Pratiti Bandopadhayay,
Rameen Beroukhim, Thomas M Roberts, Charles D Stiles, Rosalind A Segal, Keith L Ligon, William C Hahn, Jean J Zhao. Neuro-Oncology 2016. Tyrosine receptor kinase B is a drug target in astrocytoma.
60. Ting, Segal, Carandini, Voices: Opportunities for Technology and Tool Development. Neuron 2016 92, 564.
61. Yu Sun, John A Alberta, Catherine Pilarz, David Calligaris, Emily J Chadwick, Shakti H Ramkissoon, Lori A Ramkissoon, Veronica Matia Garcia, Emanuele Mazzola, Liliana Goumnerova, Michael Kane, Zhan Yao, Mark W Kieran, Keith L Ligon, William C Hahn, Levi A Garraway, Neal Rosen, Nathanael S Gray, Nathalie Y Agar, Sara J Buhrlage, Rosalind A Segal, Charles D Stiles. A brain-penentrant RAF dimer antagonist for the non-canonical BRAF oncoprotein of pediatric low grade astrocytoma. Neuro-Oncology 2017. Jun 1;19(6):774-785. doi: 10.1093/neuonc/now261 PMID:28082416
62. Pease-Raissi SE, Pazyra-Murphy MF, Li Y, Wachter F, Fukuda Y, Fenstermacher SJ, Barclay LA, Bird GH, Walensky LD, Segal RA. Paclitaxel Reduces Axonal Bclw to Initiate IP3R1-Dependent Axon Degeneration. Neuron. 2017 Oct 11;96(2):373-386.e6. doi: 10.1016/j.neuron.2017.09.034. PMID:29024661
63. Zhao X, Pak E, Ornell KJ, Pazyra-Murphy MF, MacKenzie EL, Chadwick EJ, Ponomaryov T, Kelleher JF, Segal RA. A Transposon Screen Identifies Loss of Primary Cilia as a Mechanism of Resistance to SMO Inhibitors. Cancer Discov. 2017 Sep 18. doi: 10.1158/2159-8290.CD-17-0281. PMID: 28923910
64. Fukuda Y, Li Y, Segal RA. A Mechanistic Understanding of Axon Degeneration in Chemotherapy-Induced Peripheral Neuropathy. Front Neurosci. 2017 Aug 31;11:481. doi: 10.3389/fnins.2017.00481. eCollection 2017. Review.PMID:28912674.
65. Ni J, Xie S, Ramkissoon SH, Luu V, Sun Y, Bandopadhayay P, Beroukhim R, Roberts TM, Stiles CD, Segal RA, Ligon KL, Hahn WC, Zhao JJ Tyrosine receptor kinase B is a drug target in astrocytomas. Neuro Oncol. 2017 Jan;19(1):22-30. doi: 10.1093/neuonc/now139. Epub 2016 Jul 10.PMID:27402815
Non-peer reviewed scientific or medical publications/materials in print or other media
1. Segal RA, Greenberg ME. Intracellular signaling pathways activated by neurotrophic factors. Annu Rev Neurosci. 1996;19:463-89.
2. Pomeroy SL, Segal RA. Development of the Nervous System. In: Neonatal and Fetal Medicine, Poland RA and Fox WW, eds. Philadelphia: Saunders;1997.
3. Segal RA, Rua L, Schwartz P. Neurotrophins and programmed cell death during cerebellar development. Adv Neurol. 1997;72:79-86.
4. Pomeroy SL, Sutton ME, Goumnerova LC, Segal RA. Neurotrophins in cerebellar granule cell development and medulloblastoma. J Neurooncol. 1997;35(3):347-52.
5. Alberta JA, Segal RA. Generation and utilization of phosphorylation state-specific antibodies to investigate signaling pathways. Curr Protoc Neurosci. 2001;Chapter 3:Unit 3.14.
24
6. Carter AR, Segal RA. Rett syndrome model suggests MECP2 gives neurons the quiet they need to think. Nat Neurosci. 2001;4(4):342-3.
7. Segal R. Neurotrophins: which way did they go? Sci STKE. 2001; 2001(84):pe1. 8. Heerssen HM, Segal RA. Location, location, location: a spatial view of neurotrophin signal
transduction. Trends Neurosci. 2002;25(3):160-5. 9. Ginty DD, Segal RA. Retrograde neurotrophin signaling: Trk-ing along the axon. Curr Opin
Neurobiol. 2002;12(3):268-74. 10. Rubin JB, Segal RA. Growth, survival and migration: the Trk to cancer. Cancer Treat Res.
2003;115:1-18. 11. Segal RA. Selectivity in neurotrophin signaling: theme and variations. Annu Rev Neurosci.
2003;26:299-330. 12. Kenney AM, Segal RA. Subtracting the Math: prominin-positive cerebellar stem cells in white matter.
Nat Neurosci. 2005;8(6):699-701. 13. Cosker KE, Courchesne SL, Segal RA. Action in the axon: generation and transport of signaling
endosomes. Curr Opin Neurobiol. 2008;18:270-5. PMCID: PMC2693191 14. Pazyra-Murphy MF, Segal RA. Preparation and maintenance of dorsal root ganglia neurons in
compartmented cultures. J Vis Exp. 2008;(20). pii: 951. doi: 10.3791/951. PMCID: PMC2731707 15. Witt RM, Galligan MM, Despinoy JR, Segal R. Olfactory behavioral testing in adult mouse. J Vis
Exp. 2009;(23). pii: 949. doi: 10.3791/949. PMCID: PMC2782999 16. Gruber-Filbin M, Segal RA. Live or let die: CCM2 provides the link. Neuron. 2009;63(5):559-60. 17. Kieran MW, Chi SN, Samuel D, Lechpammer M, Blackman S, Prabhu SP, Herrington B, Turner C,
Marcus KJ, Segal R. Tumors of the Brain and Spinal Cord. In: Oncology of Infancy and Childhood (1st ed), Orkin SH, Fisher DE, Look AT, Lux SE, Ginsburg D, & Nathan DG, eds. Philadelphia, PA: Saunders: 2009.
18. Cosker KE, Segal RA. The longer U(T)R, the further you go. Nat Neurosci. 2010;13(3):273-5. 19. Pake E, Segal RA, Stiles CD. New Progenitors: NESTIN(G) in the EGL Nat Neurosci. 2013;
16(12):1710-2. 20. Cosker KE and Segal RA. Neuronal Signaling through endocytosis. Cold Spring Harbor Perspect
Biol. 2014 in press, doi10.1101 . Eds. S. Schmid, A. Sorkin, M. Zerial. 21. Guillaume Bergthold, Pratiti Bandopadhayay, Wenya Linda Bi, Lori Ramkissoon, Charles Stiles ,
Rosalind A. Segal, Rameen Beroukhim, Keith L. Ligon, Jacques Grill, Mark W. Kieran, Pediatric low-grade gliomas: How modern biology reshapes the clinical field. BBA, 1845 (2014) 294–307
23. Pease, SE, Segal RA. Preserve and protect: maintaining axons within functional circuits. Trends Neuroscience. 2014 Aug 25. pii: S0166-2236(14)00123-4. doi: 10.1016/j.tins.2014.07.007. [Epub ahead of print] Review. PMID: 25167775..
24. X Zhao, RA Segal A Polyamine twist on Hedgehog signaling. Developmental cell 35 (1), 1-2 25. Pak EK, Segal RA. 2016. Hedgehog Signal Transduction: Key Player, Oncogenic Drivers and Cancer
Therapy.. Developmental Cell 38 (4), 333-344. 26. RA Segal The Bridge Generation. Science 2016 27. OE Tasdemir-Yilmaz, RA Segal. There and back again: coordinated transcription, translation and
transport in axonal survival and regeneration. Current Opintion in Neurobiology 2016, 39: 62-68.
25
Thesis
1. Segal RA. Genetic and Biochemical Dissection of the Calcium-Mediated Photophobic Response in
Chlamydomonas Reinhardtii [dissertation]. New York, New York: The Rockefeller University; February 1985.
Narrative Report
• My area of Excellence is Investigation. My research lies at the intersection of developmental neurobiology and cancer biology, and is focused on understanding growth factor pathways critical for brain development, and determining how these pathways are hijacked in brain cancers and associated neurologic disorders. My work addresses therapeutics, as growth factor signaling pathways are eminently druggable and so the disease mechanisms we identify have direct clinical implications.
A major focus over many years has been to understand the mechanisms by which neurotrophic factors, NGF and BDNF, enable neuronal differentiation and survival. We demonstrated that transport of signaling endosomes and the subsequent activation of specialized signaling pathways and transcriptional changes enable survival and function of mature sensory neurons, and so are critical for tactile sensations. Our studies identified a critical role for local translation in sensory circuit formation and function and defined a bcl2 family member (Bclw or bcl2l2) that is locally translated in sensory axons and prevents axonal degeneration and sensory neuropathy. We have addressed molecular pathways essential for axonal survival, degeneration, and regeneration and considered the implications for neurologic disorders.
A second major focus of investigation has been the function and the molecular basis for activity of the Sonic Hedgehog (Shh) signaling pathway. This pathway is critical for development of the nervous system and plays a major role in many cancers. We defined the motif within Hedgehog proteins critical for binding proteoglycans, defined the nature of the proteoglycan that serves as a selective Shh receptor and we demonstrated that proteoglycan interactions are needed for a proliferative response to Shh. We identified the chemokine SDF/CXCL12 as a major modulator of Shh signal transduction during development and oncogenesis, and we found that the retinal degeneration gene network (Eya1 and Six1) function to promote Shh-responses. Importantly, we have applied our new understanding of Shh signaling to develop novel therapeutic approaches for brain tumors.
Significant Supporting Areas are Teaching and Administration. I have consistently taught both PhD students and MD students in the classroom. I have served as a thesis advisor for eleven PhD students, one MA student, two MD honors students and eight BA students and as a member of numerous Dissertation Advisory, Preliminary Exam and Thesis Defense Committees. I have served as an advisor for Neuroscience PhD students, for MD-PhD students, for MD students in Peabody Society and for Harvard freshmen. I have had multiple administrative responsibilities, including serving as a Faculty Advisor in Science at Radcliffe, serving as the co-chair of the Dana Farber Promotions Committee, co-chair of the Strategic Planning Committee for Research, and as a member of the Executive Committee for Research. I am now the Director of the Harvard PhD program in Neuroscience, and I am a Chair of Cancer Biology at Dana-Farber Cancer Institute. My administrative roles thus encompass aspects of Student and Faculty Affairs, and new Program Development.
In the future I plan to focus my career on higher education and scientific administration. This is
an exciting and challenging time for universities. Major challenges facing higher education include 1)
26
Developing skills for rapidly changing research fields 2) Developing quantitative skills needed for future careers and the communication skills suitable for diverse media, and varied audiences 2) finding a balance between teaching and new research discoveries. 3) Ensuring that a quality education remains affordable and provides the training for rapidly evolving careers. I look forward to addressing these challenges.
