Faculty Profile: Richard Clements, PhD

Richard Clements, PhD
Assistant Professor of Surgery (Research)
Bio Med Surgery

Biography

Our main investigations are focused on mechanisms and potential treatment of myocardial stunning following surgery or ischemia. Current research focuses on the role of small heat shock proteins (sHSP) in the setting of myocardial stunning following cardioplegic arrest (solutions used to stop the heart during surgery). We demonstrate a novel role for these proteins in regulation of cardiac contraction based on phosphorylation status. Work in the laboratory is focused on elucidating mechanisms of sHSP mediated changes in cardiac function, and potential therapeutic strategies to improve heart function following surgery. There is a broad range of models used in the laboratory: including patient samples pre and post-cardiac surgery, analysis of physiology and biochemical signaling in whole heart and isolated cell models of cardiac surgery. Other areas of investigation in collaboration with Dr. Sellke's laboratory include contractile abnormalities of the coronary vasculature associated with cardiac surgery and/or cardiovascular disease risk factors.

Grants and Awards

1992–1996 Chester Arthur Undergraduate Scholarship for Excellence, Union College
1998–2000 Appointed to NIH Predoctoral Fellowship in Cardiovascular Science, T32-HL-07194
2000–2004 Trustee's Scholarship for Research, Albany Medical College.
2001 Dean's Certificate and Award for Excellence in Research, Albany Medical College
2005 - 2008 Appointed to NIH Postdoctoral Training Grant in Cardiovascular Surgery Research, T32-HL-076130-01
2006 American Heart Association Travel Award: 3rd Annual Council on Basic Cardiovascular Science.
2006-2008 Bard Memorial Fellowship in Cardiothoracic Surgery Research.
2006 Excellence in Tutorial Facilitation, Academy Center for Teaching and Learning, Harvard Medical School.
2008 Recipient: American Heart Association Scientist Development Grant
2008 Recipient: NIH-Pathway to Independence Award K99/R00
2009 Excellence in Tutorial Facilitation, Academy Center for Teaching and Learning, Harvard Medical School.
2010 Recipient: NIH Loan Repayment Program

Affiliations

2005- American Heart Association
2009- American Physiological Society
2008- Microcirculatory Society

Funded Research

National Institutes of Health, – Pathway to Independence Award
R00HL093352-01
2008-2013
PI – Richard T. Clements Ph.D.
Title: Modulation of Small Heat Shock Proteins for treatment of surgically-induced myocardial stunning.

American Heart Association Scientist Development Grant
2008-2012
P.I. - Richard T. Clements Ph.D.
Title "Modulation of small heat shock proteins for treatment of surgically-induced myocardial stunning"
(relinquished)

Selected Publications

  • Clements RT, Feng, J., Bianchi C, and Sellke, FW.. p38-MAPK-dependent Small Heat Shock Protein 27 (HSP27) and B-crystallin (cryAB) Phosphorylation in Regulation of Myocardial Function Following Cardioplegic Arrest,2011 In press: American Journal of Physiology, Heart and Circulatory Physiology. (2011)
  • Oyamada S, Bianchi C, Takai S, Robich MP, Clements RT, Chu L, Sellke FW Impact of acute myocardial ischemia reperfusion on the tissue and blood-borne renin-angiotensin system. Surgery. 2010 Aug;148(2):453-62. (2010)
  • Mieno S, Boodhwani M, Robich MP, Clements RT, Sodha NR, Sellke FW. Effects of diabetes mellitus on VEGF-induced proliferation response in bone marrow derived endothelial progenitor cells. J Card Surg. 2010 Sep;25(5):618-25. (2010)
  • Feng J, Liu Y, Khabbaz KR, Hagberg R, Robich MP, Clements RT, Bianchi C, Sellke FW. Decreased contractile response to endothelin-1 of peripheral microvasculature from diabetic patients. Surgery. 2010 Aug 19 (2010)
  • Feng J, Chu LM, Robich MP, Clements RT, Khabbaz KR, Hagberg R, Liu Y, Osipov RM, Sellke FW. Effects of cardiopulmonary bypass on endothelin-1-induced contraction and signaling in human skeletal muscle microcirculation. Circulation. 2010 Sep 14;122(11 Suppl):S150-Robich MP, Osipov RM, Nezafat R, Feng J, Clements RT, Bianchi C, Boodhwani M, Coady MA, Laham RJ, Sellke FW.Resveratrol improves myocardial perfusion in a swine model of hypercholesterolemia and chronic myocardial ischemia. Circulation. 2010 Sep 14;122(11 Suppl):S142-9. (2010)
  • Robich MP, Osipov RM, Chu LM, Feng J, Burgess TA, Oyamada S, Clements RT, Laham RJ, Sellke FW. Temporal and spatial changes in collateral formation and function during chronic myocardial ischemia. J Am Coll Surg. 2010 Oct;211(4):470-80 (2010)
  • Neel R. Sodha, Richard T. Clements, and Frank W. Sellke Vascular Changes After Cardioplegic Arrest And Cardiopulmonary Bypass: The Roles Of Nitric Oxide Synthase, Cyclooxygenase, Kinase Pathways, And Growth Factors. Frontiers in Bioscience. In press. (2009)
  • Osipov RM, Bianchi C, Clements RT, Feng J, Liu YH, Xu SH, Robich M, Wagstaff J, Sellke FW. Thrombin fragment (TP508) decreases myocardial infarction and apoptosis after ischemia reperfusion injury. Ann Thorac Surg 2009;87:786-9 (2009)
  • Sodha NR, Clements RT, Boodhwani M, Xu SH, Laham RJ, Bianchi C, Sellke FW. Endostatin and angiostatin are increased in diabetic patients with coronary artery disease and associated with impaired coronary collateral formation. Am J Physiol Heart Circ Physiol. 2009 Feb;296(2):H428-34. (2009)
  • Osipov RM, Robich MP, Feng J, Clements RT, Liu Y, Glazer HP, Wagstaff J, Bianchi C, Sellke FW Effect of thrombin fragment (TP508) on myocardial ischemia-reperfusion injury in hypercholesterolemic pigs. J Appl Physiol. 2009 Jun;106(6):1993-2001. Epub 2009 Apr 16. (2009)
  • Glazer HP, Osipov RM, Clements RT, Sellke FW, Bianchi C. Hypercholesterolemia is associated with hyperactive cardiac mTORC1 and mTORC2 signaling. Cell Cycle. 2009 Jun 1;8(11):1738-46. Epub 2009 Jun 3. (2009)
  • Osipov RM, Robich MP, Feng J, Liu Y, Clements RT, Glazer HP, Sodha NR, Szabo C, Bianchi C, Sellke FW. Effect of Hydrogen Sulfide in a Porcine Model of Myocardial Ischemia-Reperfusion: Comparison of Different Administration Regimens and Characterization of the Cellular Mechanisms of Protection. J Cardiovasc Pharmacol. 2009 Jul 17. (2009)
  • Robich MP, Araujo EG, Feng J, Osipov RM, Clements RT, Bianchi C, Sellke FW. Altered coronary microvascular serotonin receptor expression after coronary artery bypass grafting with cardiopulmonary bypass. J Thorac Cardiovasc Surg. 2009 Jul 24. (2009)
  • Sodha NR, Clements RT, Feng J, Liu Y, Bianchi C, Horvath EM, Szabo C, Stahl GL, Sellke FW.Hydrogen sulfide therapy attenuates the inflammatory response in a porcine model of myocardial ischemia/reperfusion injury. J Thorac Cardiovasc Surg. 2009 Oct;138(4):977-84. Epub 2009 Jun 13. (2009)
  • Osipov RM, Bianchi C, Feng J, Clements RT, Liu Y, Robich MP, Glazer HP, Sodha NR, Sellke FW. Effect of hypercholesterolemia on myocardial necrosis and apoptosis in the setting of ischemia-reperfusion. Circulation. 2009 Sep 15;120(11 Suppl):S22-30 (2009)
  • Clements RT, Sodha NR, Feng J, Boodhwani M, Liu YH, Mieno S, Khabbaz K, Bianchi C, Sellke FW. Impaired coronary vasodilation correlates with enhanced smooth muscle MLC phosphorylation in Diabetes. Microcirculation 2009;16:193-206. (2009)
  • Sodha NR, Boodhwani M, Clements RT, Feng J, Xu SH, Sellke FW. Coronary microvascular dysfunction in the setting of chronic ischemia is independent of arginase activity. Microvasc Res. 2008 r;75(2):238-46. (2008)
  • Sodha NR, Clements RT, Bianchi C, Sellke, FW. Cardiopulmonary Bypass with Cardioplegic Arrest Activates Protein Kinase C in the Human Myocardium. Journal of the American College of Surgeons. J Am Coll Surg 2008; 206(1);33-41. (2008)
  • Khabbaz KR, Feng J, Boodhwani M, Clements RT, Bianchi C, Sellke FW. Nonischemic myocardial acidosis adversely affects microvascular and myocardial function and triggers apoptosis during cardioplegia. J Thorac Cardiovasc Surg. 2008;135(1):139-46 (2008)
  • Sodha, NR, Boodhwani, M, Ramlawi, B, Clements, RT, Mieno, S, Feng, J, Xu, S, Bianchi, C, Sellke, FW. Atorvastatin Increases Myocardial Indices of Oxidative Stress in a Porcine Model of Hypercholesterolemia and Chronic Ischemia. J Card Surg. 2008;23(4):312-20 (2008)
  • Boodhwani M, Mieno S, Feng J, Sodha NR, Clements RT, Xu SH, Sellke FW. Atorvastatin impairs the myocardial angiogenic response to chronic ischemia in normocholesterolemic swine. J Thorac Cardiovasc Surg. 2008;135(1):117-22 (2008)
  • Sodha NR, Clements RT, Feng J, Liu Y, Bianchi C, Horvath EM, Szabo C, Sellke FW.Neel R. The Effects of Therapeutic Sulfide on Myocardial Apoptosis in Response to Ischemia – Reperfusion Injury, Eur. J. Cardiothorac and Vasc Surgery 2008; 33 (5):906-13. (2008)
  • Mieno S, Clements RT, Boodhwani M, Sodha NR, Ramlawi B, Bianchi C, Sellke FW.Characteristics and Function of Cryopreserved Bone Marrow-Derived Endothelial Progenitor Cells. Annals of Thoracic Surgery 2008:85(4):1361-6. (2008)
  • Sodha NR, Boodhwani M, Ramlawi B, Clements RT, Mieno S, Feng J, Xu SH, Bianchi C, Sellke FW. Atorvastatin increases myocardial indices of oxidative stress in a porcine model of hypercholesterolemia and chronic ischemia. J Card Surg. 2008;23(4):312-20 (2008)
  • Liu Y, Sellke EW, Feng J, Clements RT, Sodha NR, Khabbaz KR, Senthilnathan V, Alper SL, Sellke FW. Calcium-activated potassium channels contribute to human skeletal muscle microvascular endothelial dysfunction related to cardiopulmonary bypass. Surgery. 2008 Aug;144(2):239-44. (2008)
  • Feng J, Liu YH, Clements RT, Sodha NR, Khabbaz KR, Senthilnathan V, Nishimura KK, Alper SL, Sellke FW. Calcium-activated potassium channels contribute to human coronary microvascular dysfunction after cardioplegia arrest. Circulation 2008; 118 [Suppl I]: S46-S51 (2008)
  • Clements RT, Smejkal G, Sodha NR , Ivanov AR, Asara JM, Feng J, Lazarov A, Gautum S, Senthilnathan V, Khabbaz KR, Bianchi C, Sellke FW. Pilot proteomic profile of differentially regulated proteins in right atrial appendage before and after cardiac surgery using cardioplegia and cardiopulmonary bypass. Circulation. 2008; 118[Suppl I]:S24-S31 (2008)
  • Sodha NR, Boodhwani M, Clements RT, Xu SH, Khabbaz KR, Sellke FW. Increased antiangiogenic protein expression in the skeletal muscle of diabetic swine and patients. Arch Surg. 2008;143(5):463-70. (2008)
  • Sodha NR, Feng J, Clements RT, Bianchi C, Boodhwani M, Ramlawi B, Mieno S, Khabbaz KR, Sellke FW.Protein kinase C alpha modulates microvascular reactivity in the human coronary and skeletal microcirculation. Surgery. 2007;142(2):243-52 (2007)
  • Ramlawi B, Otu H, Mieno S, Boodhwani M, Sodha NR, Clements RT, Bianchi C, Sellke FW. Oxidative stress and atrial fibrillation after cardiac surgery: a case-control study. Ann Thorac Surg. 2007;84(4):1166-72. (2007)
  • Clements RT, Sodha NR, Feng J, Mieno S, Boodhwani M, Ramlawi B, Bianchi C, Sellke FW. Phosphorylation and translocation of heat shock protein 27 and alphaB-crystallin in human myocardium after cardioplegia and cardiopulmonary bypass.J Thorac Cardiovasc Surg. 2007;134(6):1461-70. (2007)
  • Boodhwani M, Sodha NR, Mieno S, Ramlawi B, Xu SH, Feng J, Clements RT, Ruel M, Sellke FW. Insulin treatment enhances the myocardial angiogenic response in diabetes.J Thorac Cardiovasc Surg. 2007;134(6):1453-60 (2007)
  • Boodhwani M, Sodha NR, Mieno S, Xu SH, Feng J, Ramlawi B, Clements RT, Sellke FW. Functional, cellular, and molecular characterization of the angiogenic response to chronic myocardial ischemia in diabetes. Circulation. 2007 11;116(11 Suppl):I31-7 (2007)
  • Boodhwani M, Feng J, Mieno S, Ramlawi B, Sodha N, Clements R, Sellke FW. Effects of purified poloxamer 407 gel on vascular occlusion and the coronary endothelium. Eur J Cardiothorac Surg. 2006;29(5):736-41 (2006)
  • Mieno S, Ramlawi B, Boodhwani M, Clements RT, Minamimura K, Maki T, Xu SH, Bianchi C, Li J, Sellke FW. Role of stromal-derived factor-1alpha in the induction of circulating CD34+CXCR4+ progenitor cells after cardiac surgery. Circulation. 2006 4;114(1 Suppl):I186-92. (2006)
  • Feng J, Sellke ME, Ramlawi B, Boodhwani M, Clements R, Li J, Bianchi C, Sellke FW. Bradykinin induces microvascular preconditioning through the opening of calcium-activated potassium channels. Surgery. 2006;140(2):192-7. (2006)
  • Mieno S, Boodhwani M, Clements RT., Ramlawi B, Sodha NR, Li J, Sellke FW. Aging is associated with an impaired coronary microvascular response to vascular endothelial growth factor in patients. J Thorac Cardiovasc Surg. 2006;132(6):1348-55 (2006)
  • Ramlawi B, Feng J, Mieno S, Szabo C, Zsengeller Z, Clements R, Sodha N, Boodhwani M, Bianchi C, Sellke FW. Indices of apoptosis activation after blood cardioplegia and cardiopulmonary bypass. Circulation. 2006 l 4;114(1 Suppl):I257-63. (2006)
  • Clements, R.T., Singer, H.A., Keller, R.S., Minnear, F.L., Vincent, P.A. RhoA and Rho-kinase dependent and independent signals mediate TGFß-induced pulmonary endothelial cytoskeletal reorganization and permeability. Am J Physiol Lung Cell Mol Physiol, 2005 Feb;288(2):L294-306. (2005)
  • Goldberg, P.L., MacNaughton, D.E., Clements, R.T., Minnear, F.L., Vincent, P.A.. P38 MAPK activation by TGF-ß1 increases MLC phosphorylation and endothelial monolayer permeability. Am J Physiol Lung Cell Mol Physiol, 282: L146-154, 2002. (2002)
  • Ferro, T.J., Clements R.T., Neumann, P.H., Gertzberg, N., Johnson, A.: Protein kinase C- mediates endothelial barrier dysfunction induced by TNF-. Am J Physiol 278:L1107-L1117, 2000. (2000)
  • Gertzberg, N., Clements R.T., Jaspers, I., Ferro, T.J., Neumann, P.H., Flescher, E., Johnson, A.: Tumor Necrosis Factor- induced Activating Protein-1 activity is modulated by nitric-oxide mediated Protein Kinase G activation. Am. J. Respir Cell Mol Biol 22:105-115, 2000. (2000)