Deepak Srivastava, MD

Director and Senior Investigator

The Younger Family Director

Phone: (415) 734-2716
Fax: (415) 355-0141
Fewer scientific details, please
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Other Professional Titles

Director, Roddenberry Center for Stem Cell Biology and Medicine

Professor, Departments of Pediatrics and Biochemistry & Biophysics, University of California, San Francisco

Wilma and Adeline Pirag Distinguished Professor in Pediatric Developmental Cardiology, University of California, San Francisco

Executive and Administrative Assistants

Bethany Taylor, Executive Assistant
(415) 734-2716
btaylor@gladstone.ucsf.edu

Karena Essex, Administrative Assistant
(415) 734-2547
kessex@gladstone.ucsf.edu

More about Dr. Srivastava

Dr. Deepak Srivastava is the Younger Family Director and a Senior Investigator at the Gladstone Institute of Cardiovascular Disease and Director of the Roddenberry Stem Cell Center at Gladstone. At the University of California, San Francisco (UCSF), Dr. Srivastava is also a Professor in the Departments of Pediatrics, and Biochemistry & Biophysics, and is the Wilma and Adeline Pirag Distinguished Professor in Pediatric Developmental Cardiology.

Dr. Srivastava’s laboratory revealed how cardiac chamber-specific gene networks are established at the transcriptional level and are integrated with signaling pathways. His laboratory used human genetics to demonstrate that a decrease in dosage of some of these cardiac developmental regulators can cause human cardiac septal defects and valve disease, and is now using induced pluripotent stem cells to discover the mechanisms of disease in these patients. In studying the regulation of gene dosage, his lab described the first known biological role of a microRNA in the mammalian system, ultimately revealing a network of microRNAs that titrate the dose of key cardiac gene networks that dictate cell fate and differentiation. Dr. Srivastava’s lab has leveraged the body of knowledge from cardiac developmental biology to reprogram non-muscle cells in the mouse heart directly into cells that function like heart muscle cells, effectively regenerating heart muscle after damage. This new paradigm of harnessing endogenous cells to regenerate organs may be broadly applicable to other organs.

Such approaches to understand human disease promise to yield new therapies. Dr. Srivastava has co-founded a biotechnology company to help find new cures for many human diseases and one of the developmental genes whose role he discovered, Thymosin b4, is currently in clinical trials for patients suffering ischemic damage to the heart.

Before joining Gladstone in 2005, Dr. Srivastava was a Professor in the Department of Pediatrics and Molecular Biology at the University of Texas Southwestern (UTSW) Medical Center in Dallas. He has received numerous honors and awards, including endowed chairs at both UTSW and UCSF, as well as election to the American Society for Clinical Investigation, the American Academy of Arts and Sciences, and the American Association for the Advancement of Science. Dr. Srivastava’s laboratory has trained more than 45 postdoctoral fellows and graduate students.

Dr. Srivastava completed his undergraduate degree at Rice University, medical training at the University of Texas Medical Branch in Galveston and his residency in the Department of Pediatrics at UCSF. He also did a fellowship in pediatric cardiology at the Children’s Hospital of Harvard Medical School and a postdoctoral fellowship at the M.D. Anderson Cancer Center, before joining the faculty at UTSW in 1996.

More scientific details, please

Other Professional Titles

Director, Roddenberry Center for Stem Cell Biology and Medicine

Professor, Departments of Pediatrics and Biochemistry & Biophysics, University of California, San Francisco

Wilma and Adeline Pirag Distinguished Professor in Pediatric Developmental Cardiology, University of California, San Francisco

Executive and Administrative Assistants

Bethany Taylor, Executive Assistant
(415) 734-2716
btaylor@gladstone.ucsf.edu

Karena Essex, Administrative Assistant
(415) 734-2547
kessex@gladstone.ucsf.edu

Areas of Investigation

My laboratory focuses on understanding the causes of heart disease and on using knowledge of cardiac developmental pathways to devise novel therapeutics for human cardiac disorders. Specifically, we study the molecular events regulating early and late developmental decisions that instruct progenitor cells to adopt a cardiac cell fate and subsequently fashion a functioning heart. We seek ways to use these pathways to prevent congenital defects and treat acquired heart disease. We also seek to identify the causes of human cardiovascular disease by applying modern genetic technologies for the study of complex traits.

Current Lab Focus

  • What are the direct targets of key transcription factors that regulate cardiogenesis and cardiomyocyte differentiation and how do they function in networks?
  • How do microRNAs regulate cardiogenesis and cardiac progenitors, and how do they integrate with transcriptional networks?
  • How do Wnt and Notch signaling intersect to regulate cardiac differentiation?
  • How can signaling, transcriptional and translational networks be manipulated to achieve direct reprogramming of non-myocytes into new cardiomyocytes for cardiac regeneration?
  • How do mutations in human disease genes, such as GATA4 and NOTCH1, and Elastin actually cause disease and how could anomalies be prevented even in the setting of mutations?
  • Do combinatorial human mutations/polymorphisms in cardiac developmental genes cause predisposition to disease?
  • How can we model human cardiovascular diseases using induced pluripotent stem cells from patients with genetically defined disease?
  • How does thymosin β4, or related pathway members, promote cardiac regeneration?

Joined Gladstone

2005

Why Gladstone?

I moved to Gladstone because of the unique combination of high quality science, focus on disease and the ability to accumulate diverse approaches on a common problem to achieve major breakthroughs. Combined with an unparalleled environment for training the next generation of scientists and a rich scientific community, Gladstone clearly stood out among its peers.

Key Achievements

  • Elucidated a cascade of transcriptional and signaling events that control the early steps of cardiomyocyte differentiation in a chamber-specific manner.
  • Found that muscle-specific histone methyltransferases and microRNAs regulate the activity of Hand2, a transcription factor essential for ventricle formation and more recently showed that microRNAs can efficiently guide stem cell fate decisions.
  • Generated the first mouse “knockout” of a microRNA and showed that even decreasing dosage of a microRNA can have dramatic consequences on multiple aspects of cardiovascular function.
  • Discovered microRNAs that direct cardiac muscle, smooth muscle, and endothelial cells from pluripotent stem cells.
  • Discovered a series of signaling events beginning with the morphogen Sonic hedgehog (Shh) that are essential for guiding a population of late cardiac progenitor cells in the outflow tract of the heart. These same cells form niches of cardiac progenitor cells postnatally. This pathway involves the transcription factor Tbx1, heterozygosity of which causes cardiac defects associated with DiGeorge syndrome.
  • Used human genetics to discover the cause of some human cardiac septal defects (GATA4) and valve diseases (NOTCH1) and revealed the mechanisms through which mutations in these genes result in anomalies.
  • Discovered that a combination of transcription factors (GATA4, TBX5, MEF2C) could reprogram cardiac fibroblasts into new induced cardiomyocytes in vivo, resulting in improved cardiac function after cardiac injury in mice.
  • Found that a developmental gene, thymosin β4, has potent properties for cardioprotection in the setting of heart attacks in mice. We are now moving this discovery into Phase II clinical trials (FDA approved) in patients suffering ischemic damage to the heart.

Education

Rice University (BA), Biochemistry (1986)
University of Texas Medical Branch (MD), Research Honors (1990)

Affiliations

Fellow, American Association for the Advancement of Science
International Society for Stem Cell Research
President, Board of Directors, American Heart Association, San Francisco chapter
National Heart, Lung and Blood Institute
American Heart Association Basic Science Council
International Society for Stem Cell Research Clinical Translation Committee
American Society of Clinical Investigators
Society for Pediatric Research

Editorial Board, Current Opinion in Genetics and Development
Editorial Board, EMBO Molecular Medicine, member of Advisory Editorial Board
Editorial Board, Circulation Research, member of Board of Consulting Editors
Editorial Board, Circulation: Cardiovascular Genetics
Editorial Board, Journal of Molecular and Cellular Cardiology
Editorial Board, Developmental Dynamics

Awards

  • University of Texas Academic Excellence Award (1986)
  • UTMB Medical Student Research Award (1990)
  • Magna Cum Laude, UTMB (1990)
  • National Institute of Health Pediatric Scientist Development Award (1993)
  • National Institute of Health Pediatric Scientist Development Award (1994)
  • National Institute of Health Pediatric Scientist Development Award (1995)
  • National Institute of Health Pediatric Scientist Development Award (1996)
  • Young Investigator Award, American Heart Association (1995)
  • Basic Science Research Award, Society for Pediatric Research (1995)
  • Louis and Arnold Katz Basic Science Award, American Heart Association, Finalist (1996)
  • Patrick J. Niland Memorial Lecturer, University of Michigan (1997)
  • Richard Rowe Award, Society for Pediatric Research (1998)
  • Young Investigator Award, Perinatal Research Society (1998)
  • Denison Young Memorial Lecturer (2000)
  • Joel B. Steinberg Chair in Pediatrics (2000)
  • Pogue Distinguished Chair in Research on Cardiac Birth Defects (2002)
  • Barbara Bowman Memorial Lecturer (2003)
  • Elected, Society for Pediatric Research (2004)
  • Award for Contributions in Medicine, Dallas Asian Chamber of Commerce (2004)
  • Elected, American Society of Clinical Investigators (2004)
  • Wilma and Adeline Pirag Distinguished Professorship in Pediatric Developmental Cardiology (2005)
  • Wendy and Leonard Goldberg Lecturer, Cedars-Sinai Medical Center (2006)
  • E. Mead Johnson Award, Society for Pediatric Research (2007)
  • Mavis P. Kelsey Lecturer, Texas Medical Center (2008)
  • Elected to the American Academy of Arts and Sciences (2010)
  • Fellow of the American Heart Association (2010)
  • Fellow of the American Association for the Advancement of Science (2011)
  • Lovett C. Peters Lecturer, Pioneer Institute (2012)
  • George E. Brown Memorial Lecturer, American Heart Association (2012)
  • Daniel McNamara Memorial Lecturer, Texas Children’s Hospital (2012)
  • Elected to the American Pediatric Society (2012)
  • Abraham White Scientific Achievement Award (2012)
  • Bay Bio Pantheon Award for Scientific Achievement (2013)
  • Best Manuscript Award, Circulation Research (2013)
  • Outstanding Investigator Award, International Society for Heart Research (2013)
  • Ashbel Smith Distinguished Alumnus Award, University of Texas Medical Branch, Galveston, TX (2013)
  • Elected to the International Academy of Cardiovascular Sciences (2014)
  • Elected to the Institute of Institute of Medicine of the National Academy of Sciences (2014)
Syndicate publications

Featured Publications

Deepak SrivastavaQian L, Huang Y, Spencer CI, Foley A, Vedantham V, Liu L, Conway SJ, Fu JD, Srivastava D. In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature. 2012 Apr 18. View in: PubMed
Deepak SrivastavaKwon C, Cheng P, King IN, Andersen P, Shenje L, Nigam V, Srivastava D. Notch post-translationally regulates ß-catenin protein in stem and progenitor cells. Nat Cell Biol. 2011 Oct; 13(10):1244-51. View in: PubMed