Post on 08-Jul-2020
transcript
1 Integrative Biology & Pharmacology Spring 2013
Month Year • Volume II Issue 3 http://ibp.med.uth.tmc.edu/
DEPARTMENTAL
NEWS & EVENTS 2 FACULTY
SPOTLIGHT 4 STUDENT
AWARDS &
ACTIVITIES 8
RESEARCH
CORNER 9 CALENDAR 10 IN THIS ISSUE
We welcome to the department Dr. Xiaodong Cheng and members of his laboratory. Dr. Cheng received his bachelor’s degree at Peking University in Beijing, China and his master’s degree in Shanghai before coming to Texas to obtain his PhD at the University of Texas Medical Branch in Galveston (UTMB). Xiaodong did his postdoctoral work with Dr. Susan Taylor at UC San Diego and then returned to UTMB in 1999 to start his own
laboratory. Xiaodong is accompanied by his wife, Dr. Fang Mei who has been a constant source of support throughout his career. Xiaodong and Fang have known each other since high school, but it wasn’t until they reunited in Beijing that they began dating and eventually married. Fang received her medical degree in Beijing and has worked as a Research Scientist for over 20 years. She began working with Xiaodong soon after he started his own lab in Galveston and is a co-author on many of his manuscripts. Xiaodong and Fang have two children; a daughter Lulu who is working for DropBox and a son Denise who is currently a student at the University of Texas in Austin. Other members of the Cheng group include Drs. Hui Wang (postdoctoral fellow with a PhD from the University of Wyoming) and Yingmin Zhu (Research Associate who obtained his PhD at the Shanghai Institutes for Biological Sciences) and two graduate students Yaohua Hu and Muayad Almahariq. Mr. Almahariq is an MD/PhD student that is currently funded by the Training Program in
Pharmacological Sciences.
The Cheng laboratory is well-known for their work on
the cAMP-dependent Rap exchanger named Epac. His
group showed that although Epac and PKA are
activated by the same second messenger, they often
exert opposing physiological effects. His lab has been
the first to examine the protein dynamics by deuterium
exchange mass spectroscopy and to identify novel
Epac selective inhibitors. Most recently, they have
developed Epac1 knockout mice to show roles for the
enzyme in diabetes and leptin signaling, and have
identified a potential use of Epac inhibitors in the
treatment of fatal rickettsioses. We are thrilled to have
Xiaodong, Fang and the rest of the Cheng laboratory
join the department and look forward to many fruitful
collaborations.
Dr. Cheng and his lab will have an open house on
Thursday, January 16th in MSB 4.410 from 4-5PM. All
are welcome to stop by and say hello!
IBP Welcomes Dr. Xiaodong Cheng & Lab Carmen Dessauer, Ph.D.
Xiaodong Cheng, Ph.D.
Professor
2 Integrative Biology & Pharmacology Spring 2013
Did you know the application used for managing Windows updates and Software deployments from Microsoft SCCM 2007-2012 has been
upgraded? It was a two-step process completed January 9-10. If you have not rebooted your computer, please do so.
Did you know
that the TMC
Library provides
training of all
kinds? Classes
are available for PubMed, RefWorks,
tracking citation rates and HTML. Check
out the website for more information.
Did you know Dr. Ilya and Kandice
Levental had a new baby recently? Emily
Lena Levantal was born in early October.
Did you know the SECC
Bake Sale here in the
department brought in
about $200? The direct
contributions totaled about
$500.
Did you know the Medical
School is switching to Word
Press to edit websites? Lisa
Byrd, who is responsible for
keeping the IBP website
updated, attended a meeting
on the use of Word Press and hopes to
have the website transitioned by the end
of January.
Did you know this newsletter is always in
search of a good story? Please send your
achievements—stories about your new
research award, recent publications,
honors/awards—to Anne Dybala.
The IBP Newsletter is published
quarterly by the department and
distributed to faculty, staff and
students. An electronic copy is
available on the IBP website at
http://ibp.med.uth.tmc.edu/
Chair, IBP
Dr. John Hancock Vice Chair, IBP Dr. Roger O’Neil Director of Management Services Monica Gardner Editor Anne Dybala Please contact any of our dedicated staff for whatever assistance you may require: Catrina Stevens Administrative Coordinator Catrina.M.Stevens@uth.tmc.edu 713.500.7536 Deborah Brougher Sr. Contracts & Grants Specialist Deborah.Brougher@uth.tmc.edu 713.500.6322 Lisa Byrd Senior Administrative Coordinator Lisa.Byrd@uth.tmc.edu 713.500.7508 Sandy Cegielski Senior Administrative Coordinator Sandy.Cegielski@uth.tmc.edu 713.500.7514 Cordelia Conley Administrative Assistant III Cordelia.P.Conley@uth.tmc.edu 713.500.7459 Anne Dybala Administrative Services Officer III Anne.L.Dybala@uth.tmc.edu 713.500.7502 Monica Gardner Director, Management Operations Monica.Gardner@uth.tmc.edu 713.500.7516 Trish McFarland Coordinator I, Educational Programs Patricia.McFarland@uth.tmc.edu 713.500.5470 Naomi Pinkney Sr. Executive Assistant Naomi.Pinkney@uth.tmc.edu 713.500.7547
Departmental News & Events
3 Integrative Biology & Pharmacology Spring 2013
New Members of the Team
Departmental News & Events
Muayad Almahariq
Visiting Student
Trainee
Dr. Cheng
Dr. Xiaodong Cheng
Professor
Sabari Arcot
Pre-Baccalaureate
Trainee
Dr. Denicourt
Yaohua Hu
Visiting Student
Trainee
Dr. Cheng
Susann Elder-
Childress
Visiting Scientist
Dr. Lichtenberger
Michael McCarthy
Graduate Research
Assistant
Dr. Loose
Fang Mei
Assistant Professor
Courtney Olsen
GSBS Graduate
Research Assistant
Dr. Schonbrunn
Yisel Rivera-Molina
Postdoctoral
Research Fellow
Dr. Berdeaux
Huai-Rong Luo
Visiting Scientist
Dr. Zhu
Hui Wang
Postdoctoral
Research Fellow
Dr. Cheng
David Waters
Research Technician
Dr. Lichtenberger
Zhong Wen
Visiting Scientist
Dr. Zhu
Emily Stockenbojer
Research Technician
Dr. Levental
4 Integrative Biology & Pharmacology Spring 2013
In an exemplary illustration of the collaborative spirit of the Department of Integrative Biology and Pharmacology, the laboratories of Dr. Levental, Dr. Hancock, and Drs. Dial and Lichtenberger have combined
forces for a recent publication showing interesting effects of bile acids on plasma membrane lateral organization. The collaboration was kindled by Drs. Lichtenberger’s and Dial’s previous work showing that unconjugated bile acids were both cytotoxic and disruptive of synthetic model membranes. Dr. Levental’s favorite model system – the Giant Plasma Membrane Vesicles – represented the ideal extension of this work, filling the gap between the relatively complex cellular systems and the fully synthetic, but experimental tractable, model membranes. As expected, cytotoxic concentrations of bile acids dissolved isolated plasma membranes, definitively validating Dr Lichtenberger’s long-standing hypothesis that the mechanism of bile acid-induced cell damage is plasmalemmal disruption.
However, a wholly unexpected effect occurred at much smaller bile acid concentrations… both common unconjugated bile acids (cholic and deoxycholic) dramatically increased the stability of lipid raft domains in isolated plasma membranes. With colleagues from Dresden, Germany, Dr. Levental characterized this effect and found it to be dependent on specific intercalation of the bile components into non-raft domains.
A (metaphorical) high-energy hallway collision between Dr Yong Zhou (the primary and co-corresponding author) and Drs Levental and Lichtenberger led to a discussion that illuminated the in vivo relevance of these observations. Independently,
Dr. Zhou (with CRB graduate students Kelsey Maxwell and Mariya Lu) had been characterizing the effects of bile acids on Ras nanoclustering in intact cell membranes and finding specific effects on the organization and signaling of the K-Ras isoform. The missing piece of the puzzle was the demonstration that bile acids had the capability of potentiating growth factor-induced oncogenic signaling through K-Ras, weaving a narrative thread from synthetic lipid membranes through to cancer.
This work was accepted for publication in the Journal of Biological Chemistry and selected for the cover of the Dec. 13
th issue. Congratulations to all
involved and thanks to the wonderful colleagues in IBP for fostering the collegial spirit of that makes such fruitful collaborations possible.
Collaboration Invasion Ilya Levental, Ph.D.
Faculty Spotlight
Welcome Emily
Lena Levental!
5 Integrative Biology & Pharmacology Spring 2013
This course is meant to provide students with a basic foundation in eukaryotic cell biology. It is offered every year in the Fall and typically enrolls about 20 students from the GSBS and the Texas A&M IBT program. For the GSBS it fulfills the “Cellular” breadth requirement. It is a team taught course with approximately 18 instructors who are generally experts in their lecture topics. The course covers four main areas, including cellular organization, structure and nuclear functions, protein/lipid synthesis and vesicle trafficking, cellular interactions with the environment, and cell growth and development. The curriculum progresses in complexity so that by the end of the course a student will have gained a fundamental understanding of how eukaryotic cells function as individual units and in the context of a multicellular organism. The specific lectures change from year to year based on instructors’ availability. In addition to the lectures, students participate in three separate journal club sessions covering 6 papers selected by instructors. The journal clubs allow the students to cover relevant topics in greater depth and to practice their analytical and presentation skills. I have had the pleasure of directing this course for the past 5 years and I find that it offers me a wonderful chance to get to know the students and to interact with a great set of instructors.
Cell Biology ~ GS04 0013 Jeff Frost
6 Integrative Biology & Pharmacology Spring 2013
Brand CS, Hocker HJ, Gorfe AA, Cavasotto CN, Dessauer CW. Isoform selectivity of adenylyl cyclase
inhibitors: characterization of known and novel compounds. J Pharmacol Exp Ther. 2013 Nov; 347(2): 265
-75.
Gong B, Shelite T, Mei F, Ha T, Xu G, Chang Q, Hu Y, Wakamiya M, Ksiazek TG, Boor PJ, Bouyer R,
Popov V, Chen J, Walker DH, Cheng X. Exchange protein directly activated by cAMP plays critical role in
fatal rickettsioses. Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19615-20.
Almahariq M, Mei F, Cheng X. Cyclic AMP Sensor EPAC Proteins and Energy Homeostasis. Trends
Endocrinol Metab. In Press.
Chen H, Wild C, Zhou X, Ye N, Cheng X, Zhou J. Recent Advances in the Discovery of Small Molecules
Targeting Exchange Proteins Directly Activated by cAMP (EPAC). J. Med. Chem. In press.
Zhou Y, Maxwell KN, Sezgin E, Lu M, Liang H, Hancock JF, Dial EJ, Lichtenberger LM, Levental I.
Bile acids modulate signaling by functional perturbation of plasma membrane domains. J Biol Chem. 2013
Dec 13;288(50):35660-70. doi: 10.1074/jbc.M113.519116. Epub 2013 Oct 28.
Yin S, Luo J, Qian A, Yu W, Hu H. LE135, a retinoid acid receptor antagonist, produces pain through
direct activation of TRP channels. Br J Pharmacol. 2013 Dec 6. doi: 10.1111/bph.12543. [Epub ahead of
print].
Luo J, Walters ET, Carlton SM and Hu H. (2013). Targeting Pain-evoking Transient Receptor Potential
Channels for the Treatment of Pain. Curr Neuropharmacol. 2013 Dec; 11 (6): 652 – 663.
Yin S*, Luo J*, Qian A, Du J, Yang Q, Zhou S, Yu W, Du G, Clark RB, Walters ET, Carlton SM, Hu H.
Retinoids activate the irritant receptor TRPV1 and produce sensory hypersensitivity. J Clin Invest. 2013
Sep 3; 123(9):3941-51.
Mamenko M, Zaika O, Pochynyuk O. Direct regulation of ENaC by Bradykinin in the distal nephron.
Implications for renal sodium handling. Curr Opin Nephrol Hypertens. 2013 ec 27 (Epub ahead of print).
Mamenko M, Zaika O, Prieto MC, Jensen VB, Doris PA, Navar LG, Pochynyuk O. Chronic Ang II
infusion drives extensive aldosterone-independent ENaC activation. Hypertension. 2013 Dec; 62(6):1111-
22.
Zaika OL, Mamenko M, Palygin O, Boukelmoune N, Staruschenko A, Pochynyuk O. Direct inhibition of
basolateral Kir4.1/5.1 and Kir4.1 channels in the cortical collecting duct by dopamine. Am J Physiol Renal
Physiol. 2013 Nov 1; 305(9): F1277-87.
Ganguly A, Yang H, Cabral F. Detection and quantification of microtubule detachment from centrosomes
and spindle poles. Methods Cell Biol. 2013;115:49-62.
Yin S, Zheng C, Hari M., Cabral F. Paclitaxel resistance by random mutagenesis of α-tubulin.
Cytoskeleton (Hoboken). 2013 Dec; 70, 849-862.
Ganguly A, Yang H, Zhang H, Cabral F, Patel KD. Microtubule dynamics control tail retraction in migrating
vascular endothelial cells. Mol. Cancer Ther. 2013 Dec; 12(12), 2837-46.
P
ub
lic
ati
on
s
7 Integrative Biology & Pharmacology Spring 2013
Reubi JC, Schonbrunn A. Illuminating somatostatin analog action at neuroendocrine tumor receptors.
Trends Pharmacol Sci. 2013 Dec; 34(12): 676 – 88.
Akhmedov D, Berdeaux R. The effects of obesity on skeletal muscle regeneration. Front Physiol. 2013
Dec 17; 4: 371.
Fu J, Akhmedov D, Berdeaux R. The short isoform of the ubiquitin ligase NEDD4L is a CREB target gene
in hepatocytes. PLoS ONE. 2013 Oct 17;8(10): e78522.
Clark RI, Tan S, Péan CB, Roostalu U, Vivancos V, Bronda K, Pilátová M, Fu J, Walker DW, Berdeaux R,
Geissmann F, Dionne MS. Mef2 is an in vivo immune-metabolic switch. Cell. 2013 Oct 10;155(2): 435-47.
Feng Z, Ziqing W, Lu M, Yonekubo Y, Liang X, Zhang Y, Wu P, Zhou Y, Grinstein S, Hancock JF, Du G;
Temporal Production of the Signaling Lipid Phosphatidic Acid by Phospholipase D2 Determines the
Output of Extracellular Signal-Regulated Kinase Signaling in Cancer Cells, Mol Cell Biol, 2014 Jan;
34(1):84-95.
Tian J, Thakur DP, Lu Y, Zhu Y, Freichel M, Flockerzi V, Zhu MX, Dual depolarization responses
generated within the same lateral septal neurons by TRPC4-containing channels; Pflugers Arch. 2013 Oct
13. [Epub ahead of print].
Feng X, Huang Y, Lu Y, Xiong J, Wong CO, Yang P, Xia J, Chen D, Du G, Venkatachalam K, Xia X,
Zhu MX, Drosophila TRPML forms PI(3,5)P2-activated cation channels in both endolysosomes and
plasma membrane, J Biol Chem. 2013 Dec 27. [Epub ahead of print].
P
ub
lic
ati
on
s
8 Integrative Biology & Pharmacology Spring 2013
Cell & Regulatory
Biology program
students Cameron
Brand from the
Dessauer lab and
Harrison Hocker of the
Gorfe lab were recently
first and second
authors on a publication in the Journal of Pharmacology
and Experimental Therapeutics (JPET) characterizing
known and novel adenylyl cyclase inhibitors. Adenylyl
cyclase signaling, through production of the second
messenger cyclic AMP, has function in cardiac muscle
among its various physiological roles. Adenylyl cyclase
inhibitors had been used extensively to explore these
roles despite previously incomplete characterization.
The more detailed profiling of these inhibitors clarified
genetic and pharmacological model inconsistencies for
adenylyl cyclase isoform 5 and 6 signaling specific to
congestive heart failure. For primarily this reason, the
article was highlighted by the journal JPET and selected
for recommendation in the Faculty of 1000 Prime
service, a directory of highly rated peer-reviewed
articles. Cameron Brand was also second-author on an
additional JPET publication that identified novel adenylyl
cyclase isoform 2 inhibitors in collaboration with Dr. Val
Watt’s laboratory at Purdue. This work was supported
in part by Cameron’s and Harrison’s fellowships from
the Training Program in Pharmacological Sciences.
Students Publish in Journal of Pharmacology and Experimental Therapeutics
Student Awards & Activities
Cameron Brand Harrison Hocker
Cameron Brand was recently awarded
the Harry S. and Isabel C. Cameron
Foundation Fellowship. This fellowship
is awarded yearly through GSBS to a
student doing research related to
cardiovascular (or Alzheimer’s)
disease. This fellowship will support
Cameron’s project to explore isoform
specific adenylyl cyclase signaling in
the context of cardiac function.
Dhananjay Thakur was awarded a
scholarship by the Graduate School of
Biomedical Sciences. Deans Michael
Blackburn and Michelle Barton
awarded Dhananjay the Investing in
Student Futures Scholarship for 2013-
2014. He received the scholarship
from the Priscilla Saunders
Endowment. The scholarship is
intended to help an exceptional GSBS
graduate student who is making
excellent progress towards his degree. Dhananjay was
selected from a highly competitive field of over 80
applicants.
Students Win Fellowship & Scholarship
Cameron Brand Dhananjay Thakur
9 Integrative Biology & Pharmacology Spring 2013
Dr. Carmen Dessauer. National Institute of General Medical Sciences. Regulation of Adenylyl Cyclase
Signaling Pathways. 9/20/2013-5/31/2017.
Dr. Hongzhen Hu. TIRR Foundation. Targeting the TRPV4 Channel to Suppress Cellular Inflammation &
Improve Locomotor & Gastrointestinal Motility Dysfunction in Spinal Cord Injury. 9/1/2013-10/15/2014.
Dr. Agi Schonbrunn. Crinetics Pharmaceuticals Inc. Biased Agonism in GPCR Drug Discovery:
Application to Somatostatin Agonists. 9/1/2013-8/31/2014.
Dr. Terry Walters. Feinstein Institute for Medical Research. Contributions of Inflammatory Mediators in
Chronic SCI. 7/1/2013-6/30/2014.
Dr. Qing Yang. Novel Target for Preventing & Ameliorating Paclitaxel-Induced Neuropathic Pain.
12/1/2013-5/16/2015.
Drs. Grill and Walters had three federal continuations this quarter.
Twenty-five proposals were submitted by the Department of Integrative
Biology & Pharmacology in the first quarter of Fiscal Year 2014 by Drs.
Berdeaux, Breton, Chang, Cheng, Denicourt, Dessauer, Du, Grill,
Hancock, Lichtenberger, Loose, Pochynyuk, Tian, Venkatachalam, and
Yang.
Five proposals were awarded this quarter along with three federal
continuations. Faculty receiving awards include Drs. Dessauer, Grill, Hu,
Schonbrunn, Walters and Yang. The success rate for awards is approximately 32% so far this year.
~Data provided by Deborah Brougher, Sr. Grants and Contracts Specialist
New Awards Awards received during the first quarter of Fiscal Year 2014 include:
R
es
ea
rc
h C
or
ne
r
Proposals & Awards Anne Dybala & Deborah Brougher
Awards Received FY2014 1st QTR
# Rec'd Federal Private State Total
5 1,319,279.00 1,319,279.00
3 130,183.00 130,183.00
8 1,319,279.00 130,183.00 - 1,449,462.00
Proposals Submitted FY2014 1st QTR
#
Submitted Federal Private State Total
20 22,869,546.00 22,869,546.00
5 2,132,108.00 2,132,108.00
25 22,869,546.00 2,132,108.00 - 25,001,654.00
10 Integrative Biology & Pharmacology Spring 2013
IBP Seminar Series
~Directed by Drs. Shane Cunha and Kartik Venkatachalam
January 13, 2014
Penney Gilbert, Ph.D.
Institute of Biomaterials & Biomedical
Engineering
University of Toronto
Bioengineering Strategies to Maintain
Skeletal Muscle Health Throughout Life
Host: Ilya Levental, Ph.D.
January 27, 2014
Rolf Konig, Ph.D.
Department of Microbiology and Immunology
University of Texas Medical Branch
Host: Jeffrey Chang, Ph.D.
February 3, 2014
Stephen Tapscott, M.D., Ph.D.
Fred Hutchinson Cancer Research Center
University of Washington School of Medicine
Regulation of gene expression in normal
muscle development and in
facioscapulohumeral muscular dystrophy
Host: Yi-Ping Li, Ph.D.
February 10, 2014
Christine Beeton, Ph.D.
Department of Physiology
Baylor College of Medicine
Targeting Potassium Channels in Chronic
Inflammatory Diseases
Host: Raymond Grill, Ph.D.
February 24, 2014
Cheryl Stucky, Ph.D.
Department of Cell Biology, Neurobiology &
Anatomy
Medical College of Wisconsin
Channeling Touch and Pain Transduction:
Mechanisms that Detect and Project
Host: Hongzhen Hu, Ph.D.
March 3, 2014
Gilbert Di Paolo, Ph.D.
Department of Pathology and Cell Biology
Columbia University Medical Center
Host: Guangwei Du, Ph.D.
March 10, 2014
Marco Sardiello, Ph.D.
Department of Molecular and Human
Genetics
Baylor College of Medicine
Host: Kartik Venkatachalam, Ph.D.
March 17, 2014
John Hancock, Bchir, Ph.D., Sc.D.
Department of Integrative Biology and
Pharmacology
University of Texas, Medical School, Houston
Host: Kartik Venkatachalam, Ph.D.
March 24, 2014
Yubin Zhou, Ph.D.
Institute of Biosciences & Technology
Texas A&M Health Science Center
Host: Michael Zhu, Ph.D.
March 31, 2014
Edgar T. Walters, Ph.D.
Department of Integrative Biology and
Pharmacology
University of Texas, Medical School, Houston
Host: Kartik Venkatachalam, Ph.D.
Seminars are held on Mondays at 4:00 PM in MSB 2.135, unless otherwise
noted. For information and questions, please contact Catrina Stevens at
catrina.m.stevens@uth.tmc.edu or
11 Integrative Biology & Pharmacology Spring 2013
IBP Seminar Series
~Directed by Drs. Shane Cunha and Kartik Venkatachalam
April 7, 2014
Boyi Gan, Ph.D.
Department of Experimental Radiation
Oncology
MD Anderson
Host: Guangwei Du, Ph.D.
April 14, 2014
Kevin Phillips, Ph.D.
Diabetes & Metabolic Disease Program
The Methodist Hospital Research Institute
Host: Rebecca Berdeaux, Ph.D.
April 21, 2014
Andrew Gladden, Ph.D.
Department of Genetics
MD Anderson
Host: Catherine Denicourt, Ph.D.
April 28, 2014
Matthias Buck, Ph.D.
Department of Pharmacology
Case Western Reserve University
Host: Alemayehu Gorfe, Ph.D.
May 5, 2014
Hoang Nguyen, Ph.D.
Department of Molecular and Cellular Biology
Baylor College of Medicine
Host: Shane Cunha
May 12, 2014
Shawn Burgess, Ph.D.
Developmental Genomics Section
National Human Genome Research Institute
Host: Ghislain Breton
May 19, 2014
Timo Rieg, M.D.
Department of Medicine
University of California San Diego
Host: Oleh Pochynyuk
Seminars are held on Mondays at 4:00 PM in MSB 2.135, unless otherwise noted. For information
and questions, please contact Catrina Stevens at catrina.m.stevens@uth.tmc.edu or
713-500-7536.
12 Integrative Biology & Pharmacology Spring 2013
Administrative Staff Meetings, 2:30-3:30 PM, MSB
4.136
January 14; February 11; March 11;
April 8; May 13
CRB Meetings, 12-1 PM, Room 4.100
February 6; March 6; April 3
Faculty Coffee/Tea, 10-11 AM, MSB 4.100
January 15, 22, 29; February 5, 12, 19,
26; March 5, 12, 19, 26; April 2, 9, 16, 23,
30
Journal Club, 3-5PM, MSB 4.100
January 23; February 6, 20; March 6, 20;
April 3, 17
STG Seminar, 4-5 PM, MSB 4.100
January 15, 22, 29; February 5, 12, 19,
26; March 5, 12, 19, 26;
April 2, 9, 16, 23, 30
Dates to Remember:
January 20: Martin Luther King Day
February 2: Groundhog Day
February 14: Valentine’s Day
February 17: President’s Day-The
University will be closed for Official
Business
March 9: Daylight Savings Time
Begins-Turn your clocks forward one
hour!
March 17: St. Patrick’s Day
April 1: April Fool’s Day
April 17-18: CRB Retreat, Camp Allen,
Navasota, TX
April 22: Earth Day
IBP Calendar of Events
CRB