Deepak Srivastava, MD

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. Srivastava’s research interests include understanding the causes of heart disease and using knowledge of cardiac developmental pathways to devise novel therapeutics for human cardiac disorders. His laboratory studies 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. These pathways may be useful in preventing congenital defects and treating acquired heart disease, particularly with cardiac-specific differentiation of embryonic stem cells. Dr. Srivastava’s lab has leveraged knowledge from developmental biology to reprogram non-muscle connective tissue in the heart directly into cells that function like heart muscle cells for regenerative purposes. Dr. Srivastava is also interested in identifying the causes of human cardiovascular disease by applying modern genetic and stem cell technologies. Such approaches to model disease in human cells promise to yield new therapies, and Dr. Srivastava has co-founded a biotechnology company to help find new cures for many human diseases.

Researchers in Dr. Srivastava’s laboratory have revealed a network of transcriptional, translational and signaling events that control the early steps of cardiomyocyte differentiation and expansion, including those involving microRNAs. His laboratory has used human genetics to discover the cause of some human cardiac septal defects and valve diseases, revealing that mutations in genes that control key networks result in cardiac anomalies. One of the developmental genes has potent properties for cardioprotection and is currently in clinical trials for patients suffering ischemic damage to the heart. Dr. Srivastava’s laboratory has trained more than 35 postdoctoral fellows and graduate students.

Before joining Gladstone, 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 Society for Pediatric Research and most recently to the American Academy of Arts and Sciences. In 2012, Dr. Srivastava presented the prestigious George E. Brown Memorial lecture to the American Heart Association. 

Dr. Srivastava completed his 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 in Houston as a Pediatric Scientist Development Program fellow, before joining the faculty at UTSW in 1996.

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)