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    Deepak Srivastava

    TitleProfessor
    SchoolUCSF School of Medicine
    DepartmentPediatrics
    Address1650 Owens St, Mission Bay
    San Francisco CA 94158
    Phone415-734-2716

       Biography 
       Education and Training
      Institution Degree School or Department Year
      University of California, San FranciscoResidency School of Medicine

       Overview 
       Overview
      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.


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       Bibliographic 
       Publications
      Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
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      1. Ang YS, Srivastava D. Oxygen: double-edged sword in cardiac function and repair. Circ Res. 2014 Oct 24; 115(10):824-5.
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      2. Hua LL, Vedantham V, Barnes RM, Hu J, Robinson AS, Bressan M, Srivastava D, Black BL. Specification of the mouse cardiac conduction system in the absence of Endothelin signaling. Dev Biol. 2014 Sep 15; 393(2):245-54.
        View in: PubMed
      3. Bruneau BG, Srivastava D. Congenital heart disease: entering a new era of human genetics. Circ Res. 2014 Feb 14; 114(4):598-9.
        View in: PubMed
      4. Srivastava D, Berry EC. Cardiac reprogramming: from mouse toward man. Curr Opin Genet Dev. 2013 Oct; 23(5):574-8.
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      5. Fu JD, Stone NR, Liu L, Spencer CI, Qian L, Hayashi Y, Delgado-Olguin P, Ding S, Bruneau BG, Srivastava D. Direct Reprogramming of Human Fibroblasts toward a Cardiomyocyte-like State. Stem Cell Reports. 2013; 1(3):235-47.
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      6. Srivastava D, Heidersbach AJ. Small solutions to big problems: microRNAs for cardiac regeneration. Circ Res. 2013 May 24; 112(11):1412-4.
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      7. Spindler MJ, Burmeister BT, Huang Y, Hsiao EC, Salomonis N, Scott MJ, Srivastava D, Carnegie GK, Conklin BR. AKAP13 Rho-GEF and PKD-binding domain deficient mice develop normally but have an abnormal response to ß-adrenergic-induced cardiac hypertrophy. PLoS One. 2013; 8(4):e62705.
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      8. Srivastava D, Cordes Metzler KR. Fending for a Braveheart. EMBO J. 2013 May 2; 32(9):1211-3.
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      9. Limphong P, Zhang H, Christians E, Liu Q, Riedel M, Ivey K, Cheng P, Mitzelfelt K, Taylor G, Winge D, Srivastava D, Benjamin I. Modeling human protein aggregation cardiomyopathy using murine induced pluripotent stem cells. Stem Cells Transl Med. 2013 Mar; 2(3):161-6.
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      10. Vedantham V, Evangelista M, Huang Y, Srivastava D. Spatiotemporal regulation of an Hcn4 enhancer defines a role for Mef2c and HDACs in cardiac electrical patterning. Dev Biol. 2013 Jan 1; 373(1):149-62.
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      11. Srivastava D, Ieda M, Fu J, Qian L. Cardiac repair with thymosin ß4 and cardiac reprogramming factors. Ann N Y Acad Sci. 2012 Oct; 1270:66-72.
        View in: PubMed
      12. Tomoda K, Takahashi K, Leung K, Okada A, Narita M, Yamada NA, Eilertson KE, Tsang P, Baba S, White MP, Sami S, Srivastava D, Conklin BR, Panning B, Yamanaka S. Derivation conditions impact X-inactivation status in female human induced pluripotent stem cells. Cell Stem Cell. 2012 Jul 6; 11(1):91-9.
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      13. Qian 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 May 31; 485(7400):593-8.
        View in: PubMed
      14. Park CY, Jeker LT, Carver-Moore K, Oh A, Liu HJ, Cameron R, Richards H, Li Z, Adler D, Yoshinaga Y, Martinez M, Nefadov M, Abbas AK, Weiss A, Lanier LL, de Jong PJ, Bluestone JA, Srivastava D, McManus MT. A resource for the conditional ablation of microRNAs in the mouse. Cell Rep. 2012 Apr 19; 1(4):385-91.
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      15. Kathiresan S, Srivastava D. Genetics of human cardiovascular disease. Cell. 2012 Mar 16; 148(6):1242-57.
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      16. Funato N, Nakamura M, Richardson JA, Srivastava D, Yanagisawa H. Tbx1 regulates oral epithelial adhesion and palatal development. Hum Mol Genet. 2012 Jun 1; 21(11):2524-37.
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      17. Bernstein HS, Srivastava D. Stem cell therapy for cardiac disease. Pediatr Res. 2012 Apr; 71(4 Pt 2):491-9.
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      18. Kwon 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.
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      19. AlRais F, Feldstein VA, Srivastava D, Gosnell K, Moon-Grady AJ. Monochorionic twins discordant for congenital heart disease: a referral center's experience and possible pathophysiologic mechanisms. Prenat Diagn. 2011 Oct; 31(10):978-84.
        View in: PubMed
      20. King IN, Qian L, Liang J, Huang Y, Shieh JT, Kwon C, Srivastava D. A genome-wide screen reveals a role for microRNA-1 in modulating cardiac cell polarity. Dev Cell. 2011 Apr 19; 20(4):497-510.
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      21. Qian L, Van Laake LW, Huang Y, Liu S, Wendland MF, Srivastava D. miR-24 inhibits apoptosis and represses Bim in mouse cardiomyocytes. J Exp Med. 2011 Mar 14; 208(3):549-60.
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      22. Srivastava D. Rudplph's Pediatrics (Rudolph C, Rudolph A, Lister G, First L, Gershon A, Eds). Control of embryologic cardiac development. 2011.
      23. Tsuchihashi T, Maeda J, Shin CH, Ivey KN, Black BL, Olson EN, Yamagishi H, Srivastava D. Hand2 function in second heart field progenitors is essential for cardiogenesis. Dev Biol. 2011 Mar 1; 351(1):62-9.
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      24. Park CY, Pierce SA, von Drehle M, Ivey KN, Morgan JA, Blau HM, Srivastava D. skNAC, a Smyd1-interacting transcription factor, is involved in cardiac development and skeletal muscle growth and regeneration. Proc Natl Acad Sci U S A. 2010 Nov 30; 107(48):20750-5.
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      25. Ieda M, Fu JD, Delgado-Olguin P, Vedantham V, Hayashi Y, Bruneau BG, Srivastava D. Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell. 2010 Aug 6; 142(3):375-86.
        View in: PubMed
      26. Ivey KN, Srivastava D. MicroRNAs as regulators of differentiation and cell fate decisions. Cell Stem Cell. 2010 Jul 2; 7(1):36-41.
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      27. Nigam V, Sievers HH, Jensen BC, Sier HA, Simpson PC, Srivastava D, Mohamed SA. Altered microRNAs in bicuspid aortic valve: a comparison between stenotic and insufficient valves. J Heart Valve Dis. 2010 Jul; 19(4):459-65.
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      28. van Laake LW, Qian L, Cheng P, Huang Y, Hsiao EC, Conklin BR, Srivastava D. Reporter-based isolation of induced pluripotent stem cell- and embryonic stem cell-derived cardiac progenitors reveals limited gene expression variance. Circ Res. 2010 Aug 6; 107(3):340-7.
        View in: PubMed
      29. Qian L, Srivastava D. Monkeying around with cardiac progenitors: hope for the future. J Clin Invest. 2010 Apr; 120(4):1034-6.
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      30. Cordes KR, Srivastava D, Ivey KN. MicroRNAs in cardiac development. Pediatr Cardiol. 2010 Apr; 31(3):349-56.
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      31. Cordes KR, Srivastava D. Heart Development and Regeneration (Rosenthal N, Harvey R, Eds). MicroRNA regulation of cardiac development and disease. 2010; 2:729–740.
      32. Bruneau BG, Burn J, Srivastava D. Paediatric Cardiology (Anderson RH, Baker EJ, Penny D, Redington AN, Rigby ML, Wernovsky G, Eds). The Aetiology of Congenital Cardiac Disease. 2010; 161–171.
      33. Nigam V, Srivastava D. Notch1 represses osteogenic pathways in aortic valve cells. J Mol Cell Cardiol. 2009 Dec; 47(6):828-34.
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      34. Kwon C, Qian L, Cheng P, Nigam V, Arnold J, Srivastava D. A regulatory pathway involving Notch1/beta-catenin/Isl1 determines cardiac progenitor cell fate. Nat Cell Biol. 2009 Aug; 11(8):951-7.
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      35. Ieda M, Tsuchihashi T, Ivey KN, Ross RS, Hong TT, Shaw RM, Srivastava D. Cardiac fibroblasts regulate myocardial proliferation through beta1 integrin signaling. Dev Cell. 2009 Feb; 16(2):233-44.
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      36. Srivastava D, Kwon C. Handbook of Cell Signaling (Bradshaw RA, Dennis EA, Eds). Signaling pathways involved in cardiogenesis. 2009; 3:2601–2609.
      37. Kwon C, Cordes KR, Srivastava D. Wnt/beta-catenin signaling acts at multiple developmental stages to promote mammalian cardiogenesis. Cell Cycle. 2008 Dec 15; 7(24):3815-8.
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      38. Morton SU, Scherz PJ, Cordes KR, Ivey KN, Stainier DY, Srivastava D. microRNA-138 modulates cardiac patterning during embryonic development. Proc Natl Acad Sci U S A. 2008 Nov 18; 105(46):17830-5.
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      39. Ransom JF, King IN, Garg V, Srivastava D. A rare human sequence variant reveals myocardin autoinhibition. J Biol Chem. 2008 Dec 19; 283(51):35845-52.
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      40. Penzes P, Cahill ME, Jones KA, Srivastava DP. Convergent CaMK and RacGEF signals control dendritic structure and function. Trends Cell Biol. 2008 Sep; 18(9):405-13.
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      41. Ivey KN, Muth A, Arnold J, King FW, Yeh RF, Fish JE, Hsiao EC, Schwartz RJ, Conklin BR, Bernstein HS, Srivastava D. MicroRNA regulation of cell lineages in mouse and human embryonic stem cells. Cell Stem Cell. 2008 Mar 6; 2(3):219-29.
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      42. Nigam V, Srivastava D. Inborn Errors of Development (Epstein CJ, Ed). Molecular regulation of cardiogenesis. 2008; 124–129.
      43. Srivastava D, Saxena A, Michael Dimaio J, Bock-Marquette I. Thymosin beta4 is cardioprotective after myocardial infarction. Ann N Y Acad Sci. 2007 Sep; 1112:161-70.
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      44. Kwon C, Arnold J, Hsiao EC, Taketo MM, Conklin BR, Srivastava D. Canonical Wnt signaling is a positive regulator of mammalian cardiac progenitors. Proc Natl Acad Sci U S A. 2007 Jun 26; 104(26):10894-9.
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      45. Pierpont ME, Basson CT, Benson DW, Gelb BD, Giglia TM, Goldmuntz E, McGee G, Sable CA, Srivastava D, Webb CL. Genetic basis for congenital heart defects: current knowledge: a scientific statement from the American Heart Association Congenital Cardiac Defects Committee, Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics. Circulation. 2007 Jun 12; 115(23):3015-38.
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      46. Zhao Y, Srivastava D. A developmental view of microRNA function. Trends Biochem Sci. 2007 Apr; 32(4):189-97.
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      47. Samal E, Srivastava D. Advances in Developmental Biology (Bodmer R, Ed). Role of microRNAs in Cardiovascular Biology. 2007; 18:167–178.
      48. Ransom J, Srivastava D. The genetics of cardiac birth defects. Semin Cell Dev Biol. 2007 Feb; 18(1):132-9.
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      49. Ivey KN, Srivastava D. The paradoxical patent ductus arteriosus. J Clin Invest. 2006 Nov; 116(11):2863-5.
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      50. Srivastava D. Making or breaking the heart: from lineage determination to morphogenesis. Cell. 2006 Sep 22; 126(6):1037-48.
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      51. Srivastava D, Yu S. Stretching to meet needs: integrin-linked kinase and the cardiac pump. Genes Dev. 2006 Sep 1; 20(17):2327-31.
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      52. Srivastava D, Ivey KN. Potential of stem-cell-based therapies for heart disease. Nature. 2006 Jun 29; 441(7097):1097-9.
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      53. King IN, Kathiriya IS, Murakami M, Nakagawa M, Gardner KA, Srivastava D, Nakagawa O. Hrt and Hes negatively regulate Notch signaling through interactions with RBP-Jkappa. Biochem Biophys Res Commun. 2006 Jun 23; 345(1):446-52.
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      54. Gong B, Trent MB, Srivastava D, Boor PJ. Chemical-induced, nonlethal, developmental model of dissecting aortic aneurysm. Birth Defects Res A Clin Mol Teratol. 2006 Jan; 76(1):29-38.
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      55. Srivastava D. Genetic regulation of cardiogenesis and congenital heart disease. Annu Rev Pathol. 2006; 1:199-213.
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      56. Kwon C, Han Z, Olson EN, Srivastava D. MicroRNA1 influences cardiac differentiation in Drosophila and regulates Notch signaling. Proc Natl Acad Sci U S A. 2005 Dec 27; 102(52):18986-91.
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      57. Garg V, Srivastava D. Principles of Molecular Cardiology (Runge MS, Patterson C, Eds). Genetic underpinnings of cardiogenesis and congenital heart disease. 2005.
      58. Srivastava D. Heart disease: an ongoing genetic battle? Nature. 2004 Jun 24; 429(6994):819-22.
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      59. Srivastava D, Olson EN. Molecular Basis of Cardiovascular Disease: A Companion to Braunwald's Heart Disease (Chien KR, Ed). Cardiac Development and Congenital Heart Disease. 2004.
      60. Srivastava D. Handbook of Cell Signaling (Bradshaw RA, Dennis EA, Eds). Signaling Pathways Involved in Cardiogenesis. 2003; 3:463–470.
      61. He F, Yang XP, Srivastava DK, Wilson SH. DNA polymerase beta gene expression: the promoter activator CREB-1 is upregulated in Chinese hamster ovary cells by DNA alkylating agent-induced stress. Biol Chem. 2003 Jan; 384(1):19-23.
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      62. Srivastava D, Gottlieb PD, Olson EN. Molecular mechanisms of ventricular hypoplasia. Cold Spring Harb Symp Quant Biol. 2002; 67:121-5.
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      63. Srivastava D. Neonatal Cardiology (Artman M, Mahony L, Teitel DF, Eds). Molecular and morphogenetic cardiac embryology: Implications for congenital heart disease. 2002; 1–15.
      64. Yamagishi H, Yamagishi C, Nakagawa O, Harvey RP, Olson EN, Srivastava D. The combinatorial activities of Nkx2.5 and dHAND are essential for cardiac ventricle formation. Dev Biol. 2001 Nov 15; 239(2):190-203.
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      65. Kunte A, Ivey K, Yamagishi C, Garg V, Yamagishi H, Srivastava D. A common cis-acting sequence in the DiGeorge critical region regulates bi-directional transcription of UFD1L and CDC45L. Mech Dev. 2001 Oct; 108(1-2):81-92.
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      66. Natarajan A, Yamagishi H, Ahmad F, Li D, Roberts R, Matsuoka R, Hill S, Srivastava D. Human eHAND, but not dHAND, is down-regulated in cardiomyopathies. J Mol Cell Cardiol. 2001 Sep; 33(9):1607-14.
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      67. Garg V, Yamagishi C, Hu T, Kathiriya IS, Yamagishi H, Srivastava D. Tbx1, a DiGeorge syndrome candidate gene, is regulated by sonic hedgehog during pharyngeal arch development. Dev Biol. 2001 Jul 1; 235(1):62-73.
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      68. Liu ZP, Nakagawa O, Nakagawa M, Yanagisawa H, Passier R, Richardson JA, Srivastava D, Olson EN. CHAMP, a novel cardiac-specific helicase regulated by MEF2C. Dev Biol. 2001 Jun 15; 234(2):497-509.
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      69. Srivastava D, Baldwin HS. Moss and Adams' Heart Disease in Infants, Children, and Adolescents (Allen HD, Gutsgell HP, Clark EB, Driscoll DJ, Eds). Molecular determinants of cardiac development. 2001.
      70. Srivastava D. Genetic assembly of the heart: implications for congenital heart disease. Annu Rev Physiol. 2001; 63:451-69.
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      71. Olson EN, Srivastava D. Encyclopedia of Molecular Medicine (Creighton TE and Kazazian HH, Eds). HAND transcription factors. 2001.
      72. Nakagawa O, McFadden DG, Nakagawa M, Yanagisawa H, Hu T, Srivastava D, Olson EN. Members of the HRT family of basic helix-loop-helix proteins act as transcriptional repressors downstream of Notch signaling. Proc Natl Acad Sci U S A. 2000 Dec 5; 97(25):13655-60.
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      73. McFadden DG, Charité J, Richardson JA, Srivastava D, Firulli AB, Olson EN. A GATA-dependent right ventricular enhancer controls dHAND transcription in the developing heart. Development. 2000 Dec; 127(24):5331-41.
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      74. Fisher SA, Langille BL, Srivastava D. Apoptosis during cardiovascular development. Circ Res. 2000 Nov 10; 87(10):856-64.
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      75. Srivastava D, Olson EN. A genetic blueprint for cardiac development. Nature. 2000 Sep 14; 407(6801):221-6.
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      76. Angelo S, Lohr J, Lee KH, Ticho BS, Breitbart RE, Hill S, Yost HJ, Srivastava D. Conservation of sequence and expression of Xenopus and zebrafish dHAND during cardiac, branchial arch and lateral mesoderm development. Mech Dev. 2000 Jul; 95(1-2):231-7.
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      77. Srivastava D. Congenital heart defects: trapping the genetic culprits. Circ Res. 2000 May 12; 86(9):917-8.
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      78. Fernandez-Teran M, Piedra ME, Kathiriya IS, Srivastava D, Rodriguez-Rey JC, Ros MA. Role of dHAND in the anterior-posterior polarization of the limb bud: implications for the Sonic hedgehog pathway. Development. 2000 May; 127(10):2133-42.
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      79. Yamagishi H, Olson EN, Srivastava D. The basic helix-loop-helix transcription factor, dHAND, is required for vascular development. J Clin Invest. 2000 Feb; 105(3):261-70.
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      80. Kathiriya IS, Srivastava D. Left-right asymmetry and cardiac looping: implications for cardiac development and congenital heart disease. Am J Med Genet. 2000; 97(4):271-9.
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      81. Yamagishi H, Srivastava D. Etiology and Morphogenesis of Congenital Heart Disease (Clark EB, Nakazawa M, Takao A, Eds). Role of the bHLH transcription factor, dHAND, in cranial/cardiac neural crest development. 2000; 325–328.
      82. Srivastava D. Etiology and Morphogenesis of Congenital Heart Disease (Takao A, Nakazawa M, Clark EB, Eds). Understanding CHD through dissection of segmental cardiac molecular pathways. 2000; 205–210.
      83. Srivastava D. DiGeorge syndrome: an enigma in mice and men. Mol Med Today. 2000 Jan; 6(1):13-4.
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      84. Nakagawa O, Nakagawa M, Richardson JA, Olson EN, Srivastava D. HRT1, HRT2, and HRT3: a new subclass of bHLH transcription factors marking specific cardiac, somitic, and pharyngeal arch segments. Dev Biol. 1999 Dec 1; 216(1):72-84.
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      85. Srivastava D, Yamagishi H. Reply: role of the dHAND-UFD1L pathway Trends Genet. 1999 Jul; 15(7):253-4.
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      86. Srivastava D. Developmental and genetic aspects of congenital heart disease. Curr Opin Cardiol. 1999 May; 14(3):263-8.
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      87. Yamagishi H, Garg V, Matsuoka R, Thomas T, Srivastava D. A molecular pathway revealing a genetic basis for human cardiac and craniofacial defects. Science. 1999 Feb 19; 283(5405):1158-61.
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      88. Srivastava D. Heart Development (Rosenthal N and Harvey R, Eds). Segmental regulation of cardiac development by the basic helix-loop-helix transcription factors dHAND and eHAND. 1999; 143–155.
      89. Srivastava D. HAND proteins: molecular mediators of cardiac development and congenital heart disease. Trends Cardiovasc Med. 1999 Jan-Feb; 9(1-2):11-8.
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      90. Thomas T, Kurihara H, Yamagishi H, Kurihara Y, Yazaki Y, Olson EN, Srivastava D. A signaling cascade involving endothelin-1, dHAND and msx1 regulates development of neural-crest-derived branchial arch mesenchyme. Development. 1998 Aug; 125(16):3005-14.
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      91. Thomas T, Yamagishi H, Overbeek PA, Olson EN, Srivastava D. The bHLH factors, dHAND and eHAND, specify pulmonary and systemic cardiac ventricles independent of left-right sidedness. Dev Biol. 1998 Apr 15; 196(2):228-36.
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      92. Firulli AB, McFadden DG, Lin Q, Srivastava D, Olson EN. Heart and extra-embryonic mesodermal defects in mouse embryos lacking the bHLH transcription factor Hand1. Nat Genet. 1998 Mar; 18(3):266-70.
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      93. Srivastava D. Left, right ... which way to turn? Nat Genet. 1997 Nov; 17(3):252-4.
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      94. Srivastava D, Olson EN. Knowing in your heart what's right. Trends Cell Biol. 1997 Nov; 7(11):447-53.
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      95. Srivastava D, Thomas T, Lin Q, Kirby ML, Brown D, Olson EN. Regulation of cardiac mesodermal and neural crest development by the bHLH transcription factor, dHAND. Nat Genet. 1997 Jun; 16(2):154-60.
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      96. Srivastava D. Genetic Control of Heart Development (Harvey RP, Olson EN, Schulz RA, Altman JS, Eds). The bHLH proteins, dHAND and eHAND in cardiac development. 1997.
      97. Lin Q, Srivastava D, Olson EN. A transcriptional pathway for cardiac development. Cold Spring Harb Symp Quant Biol. 1997; 62:405-11.
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      98. Srivastava D, Olson EN. Neurotrophin-3 knocks heart off Trk. Nat Med. 1996 Oct; 2(10):1069-71.
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      99. Olson EN, Srivastava D. Molecular pathways controlling heart development. Science. 1996 May 3; 272(5262):671-6.
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      100. Srivastava D, Cserjesi P, Olson EN. A subclass of bHLH proteins required for cardiac morphogenesis. Science. 1995 Dec 22; 270(5244):1995-9.
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      101. Srivastava D, Preminger T, Lock JE, Mandell V, Keane JF, Mayer JE, Kozakewich H, Spevak PJ. Hepatic venous blood and the development of pulmonary arteriovenous malformations in congenital heart disease. Circulation. 1995 Sep 1; 92(5):1217-22.
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      102. Srivastava D, Thompson EB. Two glucocorticoid binding sites on the human glucocorticoid receptor. Endocrinology. 1990 Oct; 127(4):1770-8.
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      103. Thompson EB, Srivastava D, Johnson BH. Interactions of the phenylpyrazolo steroid cortivazol with glucocorticoid receptors in steroid-sensitive and -resistant human leukemic cells. Cancer Res. 1989 Apr 15; 49(8 Suppl):2253s-2258s.
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