Paul Simpson, MD

Professor Emeritus

I am a clinical cardiologist at the San Francisco VA Medical Center treating inpatients and outpatients with heart disease since 1978. I also direct a lab at the VA, with a main goal to discover new drugs to treat heart failure, a major problem in cardiology. The lab has pursued initial findings from the early 1980s to the present, identifying a subclass of receptors for adrenaline as potential targets for a heart failure drug. Efforts in the lab are directed to this new drug, as well as discovering novel aspects of the class of adrenaline receptors. The lab has been funded continuously by the NIH and the VA, with additional important contribution from the AHA.

Education
Clinical Fellow, 1977 - Cardiology, Mass General Hospital
Resident, 1975 - Medicine, University of California
Research Fellow, 1974 - Neurobiology, NIH, NHLBI
Resident, 1972 - Medicine, Mass General Hospital
MD, 1970 - Medicine, Washington Univ School of Medicine
BS, 1966 - Biology & Psychology, Davidson College
Publications
  1. Myagmar BE, Ismaili T, Swigart P, Raghunathan A, Baker AJ, Sahdeo S, Blevitt JM, Milla ME, Simpson PC. Coupling to Gq Signaling Is Required for Cardioprotection by an Alpha-1A-Adrenergic Receptor Agonist. 2019. PMID: 31426700


  2. Cowley PM, Wang G, Swigart PM, Raghunathan A, Reddy NP, Dulam P, Lovett DH, Simpson PC, Baker AJ. Reversal of Right Ventricular failure by Chronic α1A-Subtype Adrenergic Agonist Therapy. 2018. PMID: 30412439


  3. Cowley PM, Wang G, Joshi S, Swigart PM, Lovett DH, Simpson PC, Baker AJ. a1A-Subtype adrenergic agonist therapy for the failing right ventricle. 2017. PMID: 28822963


  4. López JE, Sharma J, Avila J, Wood TS, VanDyke JE, McLaughlin B, Abbey CK, Wong A, Myagmar BE, Swigart PM, Simpson PC, Chiamvimonvat N. Novel large-particle FACS purification of adult ventricular myocytes reveals accumulation of myosin and actin disproportionate to cell size and proteome in normal post-weaning development. 2017. PMID: 28780067


  5. Myagmar BE, Flynn JM, Cowley PM, Swigart PM, Montgomery MD, Thai K, Nair D, Gupta R, Deng DX, Hosoda C, Melov S, Baker AJ, Simpson PC. Adrenergic Receptors in Individual Ventricular Myocytes: The Beta-1 and Alpha-1B Are in All Cells, the Alpha-1A Is in a Subpopulation, and the Beta-2 and Beta-3 Are Mostly Absent. 2017. PMID: 28219977


  6. Beak J, Huang W, Parker JS, Hicks ST, Patterson C, Simpson PC, Ma A, Jin J, Jensen BC. An Oral Selective Alpha-1A Adrenergic Receptor Agonist Prevents Doxorubicin Cardiotoxicity. 2017. PMID: 28286875


  7. Montgomery MD, Chan T, Swigart PM, Myagmar BE, Dash R, Simpson PC. An Alpha-1A Adrenergic Receptor Agonist Prevents Acute Doxorubicin Cardiomyopathy in Male Mice. 2017. PMID: 28081170


  8. Thomas RC, Cowley PM, Singh A, Myagmar BE, Swigart PM, Baker AJ, Simpson PC. The Alpha-1A Adrenergic Receptor in the Rabbit Heart. 2016. PMID: 27258143


  9. Thomas RC, Singh A, Cowley P, Myagmar BE, Montgomery MD, Swigart PM, De Marco T, Baker AJ, Simpson PC. A Myocardial Slice Culture Model Reveals Alpha-1A-Adrenergic Receptor Signaling in the Human Heart. 2016. PMID: 27453955


  10. Cowley PM, Wang G, Chang AN, Makwana O, Swigart PM, Lovett DH, Stull JT, Simpson PC, Baker AJ. The a1A-adrenergic receptor subtype mediates increased contraction of failing right ventricular myocardium. 2015. PMID: 26116709


  11. Shimkunas R, Makwana O, Spaulding K, Bazargan M, Khazalpour M, Takaba K, Soleimani M, Myagmar BE, Lovett DH, Simpson PC, Ratcliffe MB, Baker AJ. Myofilament dysfunction contributes to impaired myocardial contraction in the infarct border zone. 2014. PMID: 25128171


  12. Chu C, Thai K, Park KW, Wang P, Makwana O, Lovett DH, Simpson PC, Baker AJ. Intraventricular and interventricular cellular heterogeneity of inotropic responses to a(1)-adrenergic stimulation. 2013. PMID: 23355341


  13. Lam J, Simpson PC, Yang PC, Dash R. Synthesis of an in vivo MRI-detectable apoptosis probe. 2012. PMID: 22871963


  14. May D, Blow MJ, Kaplan T, McCulley DJ, Jensen BC, Akiyama JA, Holt A, Plajzer-Frick I, Shoukry M, Wright C, Afzal V, Simpson PC, Rubin EM, Black BL, Bristow J, Pennacchio LA, Visel A. Large-scale discovery of enhancers from human heart tissue. 2011. PMID: 22138689


  15. Doze VA, Papay RS, Goldenstein BL, Gupta MK, Collette KM, Nelson BW, Lyons MJ, Davis BA, Luger EJ, Wood SG, Haselton JR, Simpson PC, Perez DM. Long-term a1A-adrenergic receptor stimulation improves synaptic plasticity, cognitive function, mood, and longevity. 2011. PMID: 21791575


  16. López JE, Myagmar BE, Swigart PM, Montgomery MD, Haynam S, Bigos M, Rodrigo MC, Simpson PC. ß-myosin heavy chain is induced by pressure overload in a minor subpopulation of smaller mouse cardiac myocytes. 2011. PMID: 21778428


  17. Dash R, Chung J, Chan T, Yamada M, Barral J, Nishimura D, Yang PC, Simpson PC. A molecular MRI probe to detect treatment of cardiac apoptosis in vivo. 2011. PMID: 21360750


  18. Jensen BC, O'Connell TD, Simpson PC. Alpha-1-adrenergic receptors: targets for agonist drugs to treat heart failure. 2010. PMID: 21118696


  19. Jensen BC, Swigart PM, Montgomery MD, Simpson PC. Functional alpha-1B adrenergic receptors on human epicardial coronary artery endothelial cells. 2010. PMID: 20857090


  20. 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. 2010. PMID: 20845893


  21. Yeh CC, Li H, Malhotra D, Turcato S, Nicholas S, Tu R, Zhu BQ, Cha J, Swigart PM, Myagmar BE, Baker AJ, Simpson PC, Mann MJ. Distinctive ERK and p38 signaling in remote and infarcted myocardium during post-MI remodeling in the mouse. 2010. PMID: 20186881


  22. Smyth JW, Hong TT, Gao D, Vogan JM, Jensen BC, Fong TS, Simpson PC, Stainier DY, Chi NC, Shaw RM. Limited forward trafficking of connexin 43 reduces cell-cell coupling in stressed human and mouse myocardium. 2009. PMID: 20038810


  23. Wang GY, Yeh CC, Jensen BC, Mann MJ, Simpson PC, Baker AJ. Heart failure switches the RV alpha1-adrenergic inotropic response from negative to positive. 2009. PMID: 20035030


  24. Jensen BC, Swigart PM, Laden ME, DeMarco T, Hoopes C, Simpson PC. The alpha-1D Is the predominant alpha-1-adrenergic receptor subtype in human epicardial coronary arteries. 2009. PMID: 19761933


  25. Jensen BC, Swigart PM, De Marco T, Hoopes C, Simpson PC. {alpha}1-Adrenergic receptor subtypes in nonfailing and failing human myocardium. 2009. PMID: 19919991


  26. Jensen BC, Swigart PM, Simpson PC. Ten commercial antibodies for alpha-1-adrenergic receptor subtypes are nonspecific. 2008. PMID: 18989658


  27. Muramatsu I, Morishima S, Suzuki F, Yoshiki H, Anisuzzaman AS, Tanaka T, Rodrigo MC, Myagmar BE, Simpson PC. Identification of alpha 1L-adrenoceptor in mice and its abolition by alpha 1A-adrenoceptor gene knockout. 2008. PMID: 18806813


  28. Bao X, Lu CM, Liu F, Gu Y, Dalton ND, Zhu BQ, Foster E, Chen J, Karliner JS, Ross J, Simpson PC, Ziegler MG. Epinephrine is required for normal cardiovascular responses to stress in the phenylethanolamine N-methyltransferase knockout mouse. 2007. PMID: 17698731


  29. Hosoda C, Hiroyama M, Sanbe A, Birumachi J, Kitamura T, Cotecchia S, Simpson PC, Tsujimoto G, Tanoue A. Blockade of both alpha1A- and alpha1B-adrenergic receptor subtype signaling is required to inhibit neointimal formation in the mouse femoral artery. 2007. PMID: 17384126


  30. Huang Y, Wright CD, Merkwan CL, Baye NL, Liang Q, Simpson PC, O'Connell TD. An alpha1A-adrenergic-extracellular signal-regulated kinase survival signaling pathway in cardiac myocytes. 2007. PMID: 17283256


  31. O'Connell TD, Rodrigo MC, Simpson PC. Isolation and culture of adult mouse cardiac myocytes. 2007. PMID: 17172694


  32. Joho S, Ishizaka S, Sievers R, Foster E, Simpson PC, Grossman W. Left ventricular pressure-volume relationship in conscious mice. 2006. PMID: 16905597


  33. Papay R, Gaivin R, Jha A, McCune DF, McGrath JC, Rodrigo MC, Simpson PC, Doze VA, Perez DM. Localization of the mouse alpha1A-adrenergic receptor (AR) in the brain: alpha1AAR is expressed in neurons, GABAergic interneurons, and NG2 oligodendrocyte progenitors. 2006. PMID: 16705673


  34. Wang GY, McCloskey DT, Turcato S, Swigart PM, Simpson PC, Baker AJ. Contrasting inotropic responses to alpha1-adrenergic receptor stimulation in left versus right ventricular myocardium. 2006. PMID: 16731650


  35. O'Connell TD, Swigart PM, Rodrigo MC, Ishizaka S, Joho S, Turnbull L, Tecott LH, Baker AJ, Foster E, Grossman W, Simpson PC. Alpha1-adrenergic receptors prevent a maladaptive cardiac response to pressure overload. 2006. PMID: 16585965


  36. Turcato S, Turnbull L, Wang GY, Honbo N, Simpson PC, Karliner JS, Baker AJ. Ischemic preconditioning depends on age and gender. 2006. PMID: 16450074


  37. Turnbull L, Zhou HZ, Swigart PM, Turcato S, Karliner JS, Conklin BR, Simpson PC, Baker AJ. Sustained preconditioning induced by cardiac transgenesis with the tetracycline transactivator. 2005. PMID: 16243914


  38. Wang GY, Bergman MR, Nguyen AP, Turcato S, Swigart PM, Rodrigo MC, Simpson PC, Karliner JS, Lovett DH, Baker AJ. Cardiac transgenic matrix metalloproteinase-2 expression directly induces impaired contractility. 2005. PMID: 16183043


  39. McCloskey DT, Turnbull L, Swigart PM, Zambon AC, Turcato S, Joho S, Grossman W, Conklin BR, Simpson PC, Baker AJ. Cardiac transgenesis with the tetracycline transactivator changes myocardial function and gene expression. 2005. PMID: 15797971


  40. Rorabaugh BR, Ross SA, Gaivin RJ, Papay RS, McCune DF, Simpson PC, Perez DM. alpha1A- but not alpha1B-adrenergic receptors precondition the ischemic heart by a staurosporine-sensitive, chelerythrine-insensitive mechanism. 2005. PMID: 15639483


  41. Okoshi MP, Yan X, Okoshi K, Nakayama M, Schuldt AJ, O'Connell TD, Simpson PC, Lorell BH. Aldosterone directly stimulates cardiac myocyte hypertrophy. 2004. PMID: 15599842


  42. Ishizaka S, Sievers RE, Zhu BQ, Rodrigo MC, Joho S, Foster E, Simpson PC, Grossman W. New technique for measurement of left ventricular pressure in conscious mice. 2003. PMID: 14563661


  43. McCloskey DT, Turnbull L, Swigart P, O'Connell TD, Simpson PC, Baker AJ. Abnormal myocardial contraction in alpha(1A)- and alpha(1B)-adrenoceptor double-knockout mice. 2003. PMID: 14519431


  44. Rapp JH, Pan XM, Yu B, Swanson RA, Higashida RT, Simpson P, Saloner D. Cerebral ischemia and infarction from atheroemboli <100 microm in Size. 2003. PMID: 12855822


  45. O'Connell TD, Ishizaka S, Nakamura A, Swigart PM, Rodrigo MC, Simpson GL, Cotecchia S, Rokosh DG, Grossman W, Foster E, Simpson PC. The alpha(1A/C)- and alpha(1B)-adrenergic receptors are required for physiological cardiac hypertrophy in the double-knockout mouse. 2003. PMID: 12782680


  46. Gilman AG, Simon MI, Bourne HR, Harris BA, Long R, Ross EM, Stull JT, Taussig R, Bourne HR, Arkin AP, Cobb MH, Cyster JG, Devreotes PN, Ferrell JE, Fruman D, Gold M, Weiss A, Stull JT, Berridge MJ, Cantley LC, Catterall WA, Coughlin SR, Olson EN, Smith TF, Brugge JS, Botstein D, Dixon JE, Hunter T, Lefkowitz RJ, Pawson AJ, Sternberg PW, Varmus H, Subramaniam S, Sinkovits RS, Li J, Mock D, Ning Y, Saunders B, Sternweis PC, Hilgemann D, Scheuermann RH, DeCamp D, Hsueh R, Lin KM, Ni Y, Seaman WE, Simpson PC, O'Connell TD, Roach T, Simon MI, Choi S, Eversole-Cire P, Fraser I, Mumby MC, Zhao Y, Brekken D, Shu H, Meyer T, Chandy G, Heo WD, Liou J, O'Rourke N, Verghese M, Mumby SM, Han H, Brown HA, Forrester JS, Ivanova P, Milne SB, Casey PJ, Harden TK, Arkin AP, Doyle J, Gray ML, Meyer T, Michnick S, Schmidt MA, Toner M, Tsien RY, Natarajan M, Ranganathan R, Sambrano GR. Overview of the Alliance for Cellular Signaling. 2002. PMID: 12478301


  47. Turnbull L, McCloskey DT, O'Connell TD, Simpson PC, Baker AJ. Alpha 1-adrenergic receptor responses in alpha 1AB-AR knockout mouse hearts suggest the presence of alpha 1D-AR. 2002. PMID: 12595294


  48. McCloskey DT, Rokosh DG, O'Connell TD, Keung EC, Simpson PC, Baker AJ. Alpha(1)-adrenoceptor subtypes mediate negative inotropy in myocardium from alpha(1A/C)-knockout and wild type mice. 2002. PMID: 12234770


  49. Kinugawa K, Yonekura K, Ribeiro RC, Eto Y, Aoyagi T, Baxter JD, Camacho SA, Bristow MR, Long CS, Simpson PC. Regulation of thyroid hormone receptor isoforms in physiological and pathological cardiac hypertrophy. 2001. PMID: 11577024


  50. Nakamura A, Rokosh DG, Paccanaro M, Yee RR, Simpson PC, Grossman W, Foster E. LV systolic performance improves with development of hypertrophy after transverse aortic constriction in mice. 2001. PMID: 11514276


  51. Baker AJ, Redfern CH, Harwood MD, Simpson PC, Conklin BR. Abnormal contraction caused by expression of G(i)-coupled receptor in transgenic model of dilated cardiomyopathy. 2001. PMID: 11247776


  52. Zuzarte PC, Farrance IK, Simpson PC, Wildeman AG. Tumor cell splice variants of the transcription factor TEF-1 induced by SV40 T-antigen transformation. 2000. PMID: 11118619


  53. Yue P, Long CS, Austin R, Chang KC, Simpson PC, Massie BM. Post-infarction heart failure in the rat is associated with distinct alterations in cardiac myocyte molecular phenotype. 1998. PMID: 9737947


  54. Yue P, Massie BM, Simpson PC, Long CS. Cytokine expression increases in nonmyocytes from rats with postinfarction heart failure. 1998. PMID: 9688921


  55. Long CS, Henrich CJ, Simpson PC. A growth factor for cardiac myocytes is produced by cardiac nonmyocytes. 1991. PMID: 1801925


  56. Simpson PC, Kariya K, Karns LR, Long CS, Karliner JS. Adrenergic hormones and control of cardiac myocyte growth. 1991. PMID: 1656195


  57. Long CS, Kariya K, Karns L, Simpson PC. Sympathetic activity: modulator of myocardial hypertrophy. 1991. PMID: 1715479


  58. Long CS, Kariya K, Karns L, Simpson PC. Trophic factors for cardiac myocytes. 1990. PMID: 1965655


  59. Mochly-Rosen D, Henrich CJ, Cheever L, Khaner H, Simpson PC. A protein kinase C isozyme is translocated to cytoskeletal elements on activation. 1990. PMID: 2078573


  60. Simpson PC, Long CS, Waspe LE, Henrich CJ, Ordahl CP. Transcription of early developmental isogenes in cardiac myocyte hypertrophy. 1989. PMID: 2560798


  61. Simpson PC. Proto-oncogenes and cardiac hypertrophy. 1989. PMID: 2469381


  62. Simpson PC. Role of proto-oncogenes in myocardial hypertrophy. 1988. PMID: 2972186


  63. Starksen NF, Simpson PC, Bishopric N, Coughlin SR, Lee WM, Escobedo JA, Williams LT. Cardiac myocyte hypertrophy is associated with c-myc protooncogene expression. 1986. PMID: 3022291


  64. Karliner JS, Simpson PC, Honbo N, Woloszyn W. Mechanisms and time course of beta 1 adrenoceptor desensitisation in mammalian cardiac myocytes. 1986. PMID: 3011269


  65. Inouye IK, Massie BM, Benowitz N, Simpson P, Loge D. Antihypertensive therapy with diltiazem and comparison with hydrochlorothiazide. 1984. PMID: 6375339


  66. Inouye I, Massie B, Benowitz N, Simpson P, Loge D, Topic N. Monotherapy in mild to moderate hypertension: comparison of hydrochlorothiazide, propranolol and prazosin. 1984. PMID: 6320622


  67. Inouye I, Massie B, Loge D, Topic N, Silverstein D, Simpson P, Tubau J. Abnormal left ventricular filling: an early finding in mild to moderate systemic hypertension. 1984. PMID: 6691248


  68. Godwin JD, Axel L, Adams JR, Schiller NB, Simpson PC, Gertz EW. Computed tomography: a new method for diagnosing tumor of the heart. 1981. PMID: 7449067


  69. McGee R, Simpson P, Christian C, Mata M, Nelson P, Nirenberg M. Regulation of acetylcholine release from neuroblastoma x glioma hybrid cells. 1978. PMID: 206894


  70. Sherman WR, Simpson PC, Goodwin SL. scyllo-inositol and myo-inositol levels in tissues of the skate Raja erinacea. 1978. PMID: 318234


  71. Birnberger AC, Birnberger KL, Eliasson SG, Simpson PC. Effect of cyanide and electrical stimulation on phosphoinositide metabolism in lobster nerves. 1971. PMID: 4330289


  72. Sherman WR, Stewart MA, Simpson PC, Goodwin SL. The identification of myo-inosose-2 and scyllo-inositol in mammalian tissues. 1968. PMID: 5644141