Paul Simpson, MD

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. Sandroni PB, Schroder MA, Hawkins HT, Bailon JD, Huang W, Hagen JT, Montgomery M, Hong SJ, Chin AL, Zhang J, Rodrigo MC, Kim B, Simpson PC, Schisler JC, Ellis JM, Fisher-Wellman KH, Jensen BC. The alpha-1A adrenergic receptor regulates mitochondrial oxidative metabolism in the mouse heart. Journal of molecular and cellular cardiology 2024. PMID: 38331556


  2. Zhang J, Sandroni PB, Huang W, Gao X, Oswalt L, Schroder MA, Lee S, Shih YI, Huang HS, Swigart PM, Myagmar BE, Simpson PC, Rossi JS, Schisler JC, Jensen BC. Cardiomyocyte Alpha-1A Adrenergic Receptors Mitigate Postinfarct Remodeling and Mortality by Constraining Necroptosis. JACC. Basic to translational science 2023. PMID: 38362342


  3. Reitman ME, Tse V, Mi X, Willoughby DD, Peinado A, Aivazidis A, Myagmar BE, Simpson PC, Bayraktar OA, Yu G, Poskanzer KE. Norepinephrine links astrocytic activity to regulation of cortical state. Nature neuroscience 2023. PMID: 36997759


  4. Zhang J, Simpson PC, Jensen B. Cardiac alpha-1A-adrenergic receptors: emerging protective roles in cardiovascular diseases. American journal of physiology. Heart and circulatory physiology 2020. PMID: 33275531


  5. 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. Circulation research 2019. PMID: 31426700


  6. 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. American journal of physiology. Heart and circulatory physiology 2018. PMID: 30412439


  8. López JE, Jaradeh K, Silva E, Aminololama-Shakeri S, Simpson PC. A method to increase reproducibility in adult ventricular myocyte sizing and flow cytometry: Avoiding cell size bias in single cell preparations. PloS one 2017. PMID: 29084228


  9. Cowley PM, Wang G, Joshi S, Swigart PM, Lovett DH, Simpson PC, Baker AJ. a1A-Subtype adrenergic agonist therapy for the failing right ventricle. American journal of physiology. Heart and circulatory physiology 2017. PMID: 28822963


  10. 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


  12. 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. Circulation research 2017. PMID: 28219977


  13. 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


  14. 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. PloS one 2017. PMID: 28081170


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


  17. 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. JACC. Basic to translational science 2016. PMID: 27453955


  19. 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. American journal of physiology. Heart and circulatory physiology 2015. PMID: 26116709


  20. 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. American journal of physiology. Heart and circulatory physiology 2014. PMID: 25128171


  22. O'Connell TD, Jensen BC, Baker AJ, Simpson PC. Cardiac alpha1-adrenergic receptors: novel aspects of expression, signaling mechanisms, physiologic function, and clinical importance. Pharmacological reviews 2013. PMID: 24368739


  23. 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. American journal of physiology. Heart and circulatory physiology 2013. PMID: 23355341


  24. Lam J, Simpson PC, Yang PC, Dash R. Synthesis of an in vivo MRI-detectable apoptosis probe. Journal of visualized experiments : JoVE 2012. PMID: 22871963


  25. 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


  27. 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


  28. 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


  29. 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. Magnetic resonance in medicine 2011. PMID: 21360750


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


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


  32. 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


  33. 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. Journal of cellular biochemistry 2010. PMID: 20186881


  34. 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. The Journal of clinical investigation 2009. PMID: 20038810


  35. 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. American journal of physiology. Heart and circulatory physiology 2009. PMID: 20035030


  37. 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. Journal of the American College of Cardiology 2009. PMID: 19761933


  38. 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


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


  40. 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


  41. 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. Circulation 2007. PMID: 17698731


  42. 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. American journal of physiology. Heart and circulatory physiology 2007. PMID: 17384126


  43. 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. Circulation 2007. PMID: 17283256


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


  45. Joho S, Ishizaka S, Sievers R, Foster E, Simpson PC, Grossman W. Left ventricular pressure-volume relationship in conscious mice. American journal of physiology. Heart and circulatory physiology 2006. PMID: 16905597


  46. 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


  47. 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. American journal of physiology. Heart and circulatory physiology 2006. PMID: 16731650


  48. 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. The Journal of clinical investigation 2006. PMID: 16585965


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


  50. 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. American journal of physiology. Heart and circulatory physiology 2005. PMID: 16243914


  51. 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. Cardiovascular research 2005. PMID: 16183043


  53. 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. Physiological genomics 2005. PMID: 15797971


  54. 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


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


  56. 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. American journal of physiology. Heart and circulatory physiology 2003. PMID: 14563661


  57. 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. Journal of molecular and cellular cardiology 2003. PMID: 14519431


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


  59. 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. The Journal of clinical investigation 2003. PMID: 12782680


  61. 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


  62. 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. American journal of physiology. Heart and circulatory physiology 2002. PMID: 12595294


  63. 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. Journal of molecular and cellular cardiology 2002. PMID: 12234770


  64. Rokosh DG, Simpson PC. Knockout of the alpha 1A/C-adrenergic receptor subtype: the alpha 1A/C is expressed in resistance arteries and is required to maintain arterial blood pressure. Proceedings of the National Academy of Sciences of the United States of America 2002. PMID: 12093905


  65. 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


  66. 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. American journal of physiology. Heart and circulatory physiology 2001. PMID: 11514276


  68. 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. American journal of physiology. Heart and circulatory physiology 2001. PMID: 11247776


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


  72. 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


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


  74. Chang KC, Figueredo VM, Schreur JH, Kariya K, Weiner MW, Simpson PC, Camacho SA. Thyroid hormone improves function and Ca2+ handling in pressure overload hypertrophy. Association with increased sarcoplasmic reticulum Ca2+-ATPase and alpha-myosin heavy chain in rat hearts. The Journal of clinical investigation 1997. PMID: 9312172


  78. Rokosh DG, Bailey BA, Stewart AF, Karns LR, Long CS, Simpson PC. Distribution of alpha 1C-adrenergic receptor mRNA in adult rat tissues by RNase protection assay and comparison with alpha 1B and alpha 1D. Biochemical and biophysical research communications 1994. PMID: 8185565


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


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


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


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


  88. 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


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


  92. Long CS, Ordahl CP, Simpson PC. Alpha 1-adrenergic receptor stimulation of sarcomeric actin isogene transcription in hypertrophy of cultured rat heart muscle cells. The Journal of clinical investigation 1989. PMID: 2537847


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


  96. Simpson PC. Role of proto-oncogenes in myocardial hypertrophy. The American journal of cardiology 1988. PMID: 2972186


  98. Bishopric NH, Simpson PC, Ordahl CP. Induction of the skeletal alpha-actin gene in alpha 1-adrenoceptor-mediated hypertrophy of rat cardiac myocytes. The Journal of clinical investigation 1987. PMID: 2821075


  99. Starksen NF, Simpson PC, Bishopric N, Coughlin SR, Lee WM, Escobedo JA, Williams LT. Cardiac myocyte hypertrophy is associated with c-myc protooncogene expression. Proceedings of the National Academy of Sciences of the United States of America 1986. PMID: 3022291


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


  102. Karliner JS, Simpson PC, Taylor JE, Honbo N, Woloszyn W. Adrenergic receptor characteristics of cardiac myocytes cultured in serum-free medium: comparison with serum-supplemented medium. Biochemical and biophysical research communications 1985. PMID: 3985976


  103. Inouye IK, Massie BM, Benowitz N, Simpson P, Loge D. Antihypertensive therapy with diltiazem and comparison with hydrochlorothiazide. The American journal of cardiology 1984. PMID: 6375339


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


  106. 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. The American journal of cardiology 1984. PMID: 6691248


  107. Simpson P. Norepinephrine-stimulated hypertrophy of cultured rat myocardial cells is an alpha 1 adrenergic response. The Journal of clinical investigation 1983. PMID: 6135712


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


  111. McGee R, Simpson P, Christian C, Mata M, Nelson P, Nirenberg M. Regulation of acetylcholine release from neuroblastoma x glioma hybrid cells. Proceedings of the National Academy of Sciences of the United States of America 1978. PMID: 206894


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


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


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