Deepak Srivastava, MD

Professor
M_PEDS-CARDIOLOGY
+1 415 734-2716

Our laboratory focuses on understanding the causes of heart disease and on using knowledge of cardiac developmental pathways to devise novel therapeutic approaches 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 focus on transcriptional and post-transcriptional steps, including those involving microRNAs. We have leveraged this knowledge to reprogram fibroblasts directly into cardiomyocyte-like cells for regenerative purposes. We also seek to identify the causes of human cardiovascular disease by applying modern genetic technologies for the study of complex traits such as congenital heart disease. By using a spectrum of approaches including mouse and human genetics, molecular and developmental biology, and biochemistry we hope to develop a broad understanding of the biology underlying cardiogenesis and cardiovascular disorders.

Publications

Genomic analysis of 11,555 probands identifies 60 dominant congenital heart disease genes.

Proceedings of the National Academy of Sciences of the United States of America

Sierant MC, Jin SC, Bilguvar K, Morton SU, Dong W, Jiang W, Lu Z, Li B, López-Giráldez F, Tikhonova I, Zeng X, Lu Q, Choi J, Zhang J, Nelson-Williams C, Knight JR, Zhao H, Cao J, Mane S, Sedore SC, Gruber PJ, Lek M, Goldmuntz E, Deanfield J, Giardini A, Mital S, Russell M, Gaynor JW, King E, Wagner M, Srivastava D, Shen Y, Bernstein D, Porter GA, Newburger JW, Seidman JG, Roberts AE, Yandell M, Yost HJ, Tristani-Firouzi M, Kim R, Chung WK, Gelb BD, Seidman CE, Brueckner M, Lifton RP

Recessive genetic contribution to congenital heart disease in 5,424 probands.

Proceedings of the National Academy of Sciences of the United States of America

Dong W, Jin SC, Sierant MC, Lu Z, Li B, Lu Q, Morton SU, Zhang J, López-Giráldez F, Nelson-Williams C, Knight JR, Zhao H, Cao J, Mane S, Gruber PJ, Lek M, Goldmuntz E, Deanfield J, Giardini A, Mital S, Russell M, Gaynor JW, Cnota JF, Wagner M, Srivastava D, Bernstein D, Porter GA, Newburger J, Roberts AE, Yandell M, Yost HJ, Tristani-Firouzi M, Kim R, Seidman J, Chung WK, Gelb BD, Seidman CE, Lifton RP, Brueckner M

Chromatin remodelling drives immune cell-fibroblast communication in heart failure.

Nature

Alexanian M, Padmanabhan A, Nishino T, Travers JG, Ye L, Pelonero A, Lee CY, Sadagopan N, Huang Y, Auclair K, Zhu A, An Y, Ekstrand CA, Martinez C, Teran BG, Flanigan WR, Kim CK, Lumbao-Conradson K, Gardner Z, Li L, Costa MW, Jain R, Charo I, Combes AJ, Haldar SM, Pollard KS, Vagnozzi RJ, McKinsey TA, Przytycki PF, Srivastava D

A genome-wide CRISPR screen identifies BRD4 as a regulator of cardiomyocyte differentiation.

Nature cardiovascular research

Arun Padmanabhan, T. Yvanka de Soysa, Angelo Pelonero, Valerie Sapp, Parisha P. Shah, Qiaohong Wang, Li Li, Clara Youngna Lee, Nandhini Sadagopan, Tomohiro Nishino, Lin Ye, Rachel Yang, Ashley Karnay, Andrey Poleshko, Nikhita Bolar, Ricardo Linares-Saldana, Sanjeev S. Ranade, Michael Alexanian, Sarah U. Morton, Mohit Jain, Saptarsi M. Haldar, Deepak Srivastava, Rajan Jain

A transcriptional switch governs fibroblast activation in heart disease.

Nature

Alexanian M, Przytycki PF, Micheletti R, Padmanabhan A, Ye L, Travers JG, Gonzalez-Teran B, Silva AC, Duan Q, Ranade SS, Felix F, Linares-Saldana R, Li L, Lee CY, Sadagopan N, Pelonero A, Huang Y, Andreoletti G, Jain R, McKinsey TA, Rosenfeld MG, Gifford CA, Pollard KS, Haldar SM, Srivastava D

De Novo Damaging Variants, Clinical Phenotypes, and Post-Operative Outcomes in Congenital Heart Disease.

Circulation. Genomic and precision medicine

Boskovski MT, Homsy J, Nathan M, Sleeper LA, Morton S, Manheimer KB, Tai A, Gorham J, Lewis M, Swartz M, Alfieris GM, Bacha EA, Karimi M, Meyer D, Nguyen K, Bernstein D, Romano-Adesman A, Porter GA, Goldmuntz E, Chung WK, Srivastava D, Kaltman JR, Tristani-Firouzi M, Lifton R, Roberts AE, Gaynor JW, Gelb BD, Kim R, Seidman JG, Brueckner M, Mayer JE, Newburger JW, Seidman CE

Genomic analyses implicate noncoding de novo variants in congenital heart disease.

Nature genetics

Richter F, Morton SU, Kim SW, Kitaygorodsky A, Wasson LK, Chen KM, Zhou J, Qi H, Patel N, DePalma SR, Parfenov M, Homsy J, Gorham JM, Manheimer KB, Velinder M, Farrell A, Marth G, Schadt EE, Kaltman JR, Newburger JW, Giardini A, Goldmuntz E, Brueckner M, Kim R, Porter GA, Bernstein D, Chung WK, Srivastava D, Tristani-Firouzi M, Troyanskaya OG, Dickel DE, Shen Y, Seidman JG, Seidman CE, Gelb BD

The Psychiatric Cell Map Initiative: A Convergent Systems Biological Approach to Illuminating Key Molecular Pathways in Neuropsychiatric Disorders.

Cell

Willsey AJ, Morris MT, Wang S, Willsey HR, Sun N, Teerikorpi N, Baum TB, Cagney G, Bender KJ, Desai TA, Srivastava D, Davis GW, Doudna J, Chang E, Sohal V, Lowenstein DH, Li H, Agard D, Keiser MJ, Shoichet B, von Zastrow M, Mucke L, Finkbeiner S, Gan L, Sestan N, Ward ME, Huttenhain R, Nowakowski TJ, Bellen HJ, Frank LM, Khokha MK, Lifton RP, Kampmann M, Ideker T, State MW, Krogan NJ

Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands.

Nature genetics

Jin SC, Homsy J, Zaidi S, Lu Q, Morton S, DePalma SR, Zeng X, Qi H, Chang W, Sierant MC, Hung WC, Haider S, Zhang J, Knight J, Bjornson RD, Castaldi C, Tikhonoa IR, Bilguvar K, Mane SM, Sanders SJ, Mital S, Russell MW, Gaynor JW, Deanfield J, Giardini A, Porter GA, Srivastava D, Lo CW, Shen Y, Watkins WS, Yandell M, Yost HJ, Tristani-Firouzi M, Newburger JW, Roberts AE, Kim R, Zhao H, Kaltman JR, Goldmuntz E, Chung WK, Seidman JG, Gelb BD, Seidman CE, Lifton RP, Brueckner M

Affiliation