Areas of Investigation

The Srivastava laboratory is focused on the complex signaling, transcriptional, and translational networks that guide early differentiation of cardiac progenitors and later morphogenetic events during cardiogenesis. By leveraging these networks, they have reprogrammed disease-specific human cells to model human heart disease in patients with mutations in cardiac developmental genes. By applying deep epigenetic and transcriptome analyses to these cells, they have discovered perturbations in pivotal gene networks which contribute to disease, and which can be corrected by altering dosage of nodal points in the network. These studies revealed mechanisms by which NOTCH1 and GATA4 haploinsufficiency drive congenital heart disease and have led to potential therapeutic approaches.

The group is also pursuing the use of a combination of cardiac regulatory factors and small molecules to directly reprogram resident cardiac fibroblasts into cardiomyocyte-like cells in vitro and in vivo to repair damaged hearts. As an alternative approach, Srivastava’s group has also identified a combination of cell-cycle regulators that efficiently induce adult cardiomyocytes to divide in a stable fashion, resulting in sufficient new muscle to regenerate infarcted hearts in vivo.

The Srivastava lab is also extensively using single cell technologies to unravel the mysteries of organ development. The group combines use of CRISPR-based screens in human pluripotent stem cells and in vivo developmental biology with single cell resolution to mechanistically interrogate the patterning and gene networks that drive normal and abnormal organogenesis.

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?


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 the 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.

Professional Society Activities and Affiliations

2017– Section Head for Developmental Biology, Faculty of 1000
2017–2018 Vice President, International Society for Stem Cell Research
2017 Annual Meeting Program Committee, International Society for Stem Cell Research
2015 Advisory Board Member, World Alliance Forum San Francisco
2014–2017 Council Member, North American Section of the International Academy of Cardiovascular Sciences
2014–2016 Program Chair, 2016 Annual Meeting, International Society for Stem Cell Research
2013–2014 Nominating Committee, American Pediatric Society
2013– Baker Institute Scholar for Biomedical Research Policy, Rice University
2013– Secretary, Board of Directors, Western States Affiliate, American Heart Association
2010– Board of Directors Member, International Society for Stem Cell Research
2010, 2012 Annual Meeting Program Committee, International Society for Stem Cell Research
2008–2013 President, Board of Directors, American Heart Association, San Francisco chapter
2007– National Heart, Lung and Blood Institute Board of External Experts
2008–2010 Program Committee, American Heart Association Basic Science Council
2008–2011 Member, International Society for Stem Cell Research Clinical Translation Committee
2006–2013 Board Member, American Heart Association, San Francisco chapter
2004– Member, American Society of Clinical Investigators
2003 Member, Society for Pediatric Research
2002–2004 Leadership Committee, American Heart Association Council on Basic Sciences
2001–2004 Member, American Heart Association, Early Career Development Program Committee
1999–2005 Board Member, March of Dimes North Texas Chapter
1993,1994 Operation Smile, Kenya
1991–93 American Academy of Pediatrics, Resident Representative to the AMA
1989–90 President, Texas Medical Association-Medical Student Section

Professional titles

Director, Roddenberry Stem Cell Center;
Professor, University of California, San Francisco


  • Rice University
  • University of Texas Medical Branch

Honors and Awards

2017 Upstart 50 Inventor Award, San Francisco Business Times
2016 Andras Varro Award for Excellence in Cardiovascular Sciences; International Academy of Cardiovascular Sciences
2015 World Affairs Council Award, San Francisco, CA
2014 Elected to the International Academy of Cardiovascular Sciences
2014 Elected to the National Academy of Medicine
2013 Ashbel Smith Distinguished Alumnus Award, University of Texas Medical Branch
2013 Bay Bio Pantheon Award for Scientific Achievement
2013 Best Manuscript Award, Circulation Research
2013 Outstanding Investigator Award, International Society for Heart Research
2012 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 American Pediatric Society (Elected)
2012 Abraham White Scientific Achievement Award
2011 American Association for the Advancement of Science (Fellow)
2010 American Heart Association (Fellow)
2010 American Academy of Arts and Sciences (Elected)
2008 Mavis P. Kelsey Lecturer, Texas Medical Center
2007 E. Mead Johnson Award, Society for Pediatric Research
2006 Wendy and Leonard Goldberg Lecturer, Cedars-Sinai Medical Center
2005 Wilma and Adeline Pirag Distinguished Professorship in Pediatric Developmental Cardiology
2004 American Society for Clinical Investigators (Elected)
2004 Society for Pediatric Research (Elected)
2004 Outstanding Contributions in Medicine Award, Dallas Asian Chamber of Commerce
2003 Barbara Bowman Memorial Lecturer
2003 American Society of Clinical Investigators
2002 Pogue Distinguished Chair in Research on Cardiac Birth Defects
2000 Denison Young Memorial Lecturer
2000 Joel B. Steinberg Chair in Pediatrics
1998 Richard Rowe Award, Society for Pediatric Research
1998 Young Investigator Award, Perinatal Research Society
1997 Patrick J. Niland Memorial Lecturer, University of Michigan
1996 National Institute of Health Pediatric Scientist Development Award
1996 Louis and Arnold Katz Basic Science Award, American Heart Association (Finalist)
1995 National Institute of Health Pediatric Scientist Development Award
1995 Young Investigator Award, American Heart Association
1995 Basic Science Research Award, Society for Pediatric Research
1994 National Institute of Health Pediatric Scientist Development Award
1993 National Institute of Health Pediatric Scientist Development Award
1990 Medical Student Research Award, University of Texas Medical Branch
1990 Magna Cum Laude, University of Texas Medical Branch
1986 University of Texas Academic Excellence Award