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Ross D. Feldman

Ross D. Feldman, Scientist, Vascular Biology; Professor, Medicine and Physiology/Pharmacology

Why I Became a Scientist

During the course of my training as a physician, I was driven both by the art and the science of medicine- especially in the workings of the heart and circulation.? More than thirty years later I am still grateful for the opportunities to decipher how the cardiovascular system works at a cellular and molecular level and how manipulating those cellular systems can either lead to blood vessel diseases or?new treatment approaches.

Research Summary

My laboratory has helped to further our understanding of how blood vessels are regulated and how those systems breakdown in blood vessel diseases- including high blood pressure.

In hypertension, a failure of blood vessels to relax properly in response to hormones is one of the most important mechanisms leading to the development of hypertension.? We discovered the molecular mechanism underlying that defect and identified the protein responsible (J Clin Invest.1997;99:2087-2093).

We now know that insulin has important effects on blood vessels- beyond its effects on regulation of glucose. We were the first to demonstrate how insulin caused blood vessel relaxation and that the ability of insulin to regulate blood vessels was impaired in diabetes, hypertension and with obesity (Lancet 1993; 342:707-709). These studies have been important in our understanding of the linkage between hypertension, diabetes and obesity.

Unraveling the cardiovascular effects of estrogen has been and remains an important question.? On one hand, the lower rate of heart disease in women has in part been attributed to estrogen.? However, post-menopausal estrogen replacement either does not protect or increases risk of cardiovascular disease.? Studies from our laboratory have delineated the cellular basis for these two sided effects of estrogen and how an imbalance in those estrogen-driven systems can lead to high blood pressure and high cholesterol levels in women- two of the most important causes of heart disease and stroke.

In addition to my biomedical research program, I continue a clinical research program.? Recent studies have focused on the development and determination of the effectiveness of novel approaches to manage hypertension and other atherosclerotic risk factors in the primary care setting.

Research Questions

Why have reproductive hormones like estrogen been linked BOTH to positive and negative?cardiovascular effects?? What are the mechanisms involved?

Estrogen has been shown to be both cardioprotective and to precipitate?cardiovascular complications.? Figuring out the different pathways that these effects are mediated by will allow the opportunity to develop more specific therapies that optimize the positive effects.

How can we improve the management of high blood pressure, high cholesterol and diabetes?

The treatment of these 2 major risk factors for heart disease remains a challenge- in part related to the complexity of therapies.? We are testing the effectiveness of a simplified approach to the treatment of these diseases.

Education

??Queen’s University, University of Toronto,?Vanderbilt University

Training

??BSc, MD, Internal Medicine residency, Post-doctoral training in Clinical Pharmacology

Awards

??Burroughs-Welcome Award in Clinical Pharmacology
??Young Investigator Award, CSCP
??ACP Scholar Award
??Career?Investigator Award HSFO
??Senior Investigator Award CSCP
??Distinguished Scientist Award CHS
??Dean’s Award of Excellence, Schulich School of Medicine
? George Fodor Award for Outstanding Contributions to the Prevention & Control of Hypertension, Hypertension Canada

Publications

? Hussain Y, Ding Q, Connelly PW, Brunt JH, Ban MR, McIntyre AD, Huff MW, Gros R, Hegele RA, Feldman RD. G-protein estrogen receptor as a regulator of low-density lipoprotein cholesterol metabolism: cellular and population genetic studies. Arterioscler Thromb Vasc Biol 2015 Jan;35(1):213-221.

? Kjeldsen S, Feldman RD, Lisheng L, Mourad JJ, Chiang CE, Zhang W, Wu Z, Li W, Williams B. Updated national and international hypertension guidelines: a reveiw of current recommendations. Drugs 2014 Nov;74(17):2033-2051.

? Feldman RD, Hussain Y, Kuyper LM, McAlister FA, Padwal RS, Tobe SW. Intra-class differences among antihypertensive drugs. Ann Rev Pharmacol Toxicol 2015 Jan;55:333-352.

? Lother A, Moser M, Bode C, Feldman RD, Hein L. Mineralocorticoids in heart and vasculature: new insights for old hormones. Ann Rev Pharmacol Toxicol 2015 Jan;55:289-312.

? Ding Q, Hussain Y, Chorazyczewski J, Gros R, Feldman RD. GPER-independent effects of estrogen in rat aortic vascular endothial cells. Mol Cell Endocrinol 2015 Jan;399:60-68.

? Feldman RD, Gros R, Ding Q, Hussain Y, Ban MR, McIntyre AD, Hegele RA. A common hypofunctional genetic variant of GPER is associated with increased blood pressure in women. Br J Clin Pharmacol 2014 Dec:78(6):1441-1452.

? Rash JA, Lavoie KL, Feldman RD, Campbell TS. Adherence to antihypertensive medications: current status and future directions. Curr Cardiovasc Risk Rep 2014 8(12):1-13.

? Feldman RD, Nattel S. Increasing appreciation for the role of single pill combinations for the prevention of atherosclerotic disease: a pro-polypill polemic. Can J Cardiol 2014 May;30(5):517-519.

? Dasgupta K, Quinn RR, Zarnke KB, Rabi DM, Ravani P, Daskalopoulou SS, Rabkin SW, Trudeau L, Feldman RD, Cloutier L, Prebtani A, Herman RJ, Bacon SL, Gilbert RE, Ruzicka M, McKay DM, Campbell TS, Grover S, Honos G, Schiffrin EL, Bolli P, Wilson TW, Lindsay P, Hill MD, Coutts SB, Gubitz G, Gelfer M, Vallée M, Prasad GV, Lebel M, McLean D, Arnold JM, Moe GW, Howlett JG, Boulanger JM, Larochelle P, Leiter LA, Jones C, Ogilvie RI, Woo V, Kaczorowski J, Burns KD, Petrella RJ, Hiremath S, Milot A, Stone JA, Drouin D, Lavoie KL, Lamare-Cliche M, Tremblay G, Hamet P, Foder G, Carruthers SG, Pylypchuk GB, Burgess E, Lewanczuk R, Dresser GK, Penner SB, Hegele RA, McFarlane PA, Khara M, Pipe A, Oh P, Selby P, Sharma M, Reid D, Tobe SW, Padwal RS, Poirier L. The 2014 Canadian Hypertension Education Program (CHEP) recommendations for blood presure measurement, diagnosis, assessment of risk, prevention and treatment of hypertension. Can J Cardiol 2014 May;30(5):485-501.

? Ferguson SSG, Feldman RD. Beta adrenoceptors as molecular targets in the treatment of hypertension. Can J Cardiol 2014 May;30(5S):S3-S8.

? Khan NA, Herman RJ, Quinn RR, Rabkin SW, Ravani P, Tobe SW, Feldman RD, et al. Renal denervation therapy for the treatment of resistant hypertension: a position statement by the Canadian Hypertension Education Program. Can J Cardiol 2014 Jan;30(1):16-21.

? Feldman RD. Aldosterone and blood pressure regulation: recent milestones on the long and winding road from electrocortin to KCNJ5, GPER, and beyond. Hypertens 2014 Jan;63(1):19-21.

? Feldman RD, Gros R. Vascular effects of aldosterone: sorting out the receptors and the ligands. Clin Exp Pharmcol Physiol 2013 Dec;40(12):916-921.

? Dresser GK, Nelson SAE, Mahon JL, Zou G, Vandervoort MK, Wong CJ, Feagan BG, Feldman RD. Simplified therapeutic intervention to control hypertension and hypercholesterolemia: a cluster reandomized controlled trial (STITCH2). J Hypertens 2013 Aug;31(8):1702-1713.

? Feldman RD, Brass EP. From bad behavior to bad biology: pitfalls and promises in the management of resistant hypertension. Can J Cardiol 2013 May;29(5):549-556.

? Hackam DG, Quinn RR, Ravani P, Rabi DM, Dasgupta K, Daskalopoulou SS, Khan NA, Herman RJ, Bacon SL, Cloutier L, Dawes M, Rabkin SW, Gilbert RE, Ruzicka M, McKay DW, Campbell TS, Grover S, Honos G, Schiffrin EL, Bolli P, Wilson TW, Feldman RD, Lindsay P, Hill MD, Gelfer M, Burns KD, Vallée M, Prasad GV, Lebel M, McLean D, Arnold JM, Moe GW, Howlett JG, Boulanger JM, Larochelle P, Leiter LA, Jones C, Ogilvie RI, Woo V, Kaczorowski J, Trudeau L, Petrella RJ, Milot A, Stone JA, Drouin D, Lavoie KL, Lamarre-Cliche M, Godwin M, Tremblay G, Hamet P, Fodor G, Carruthers SG, Pylypchuk GB, Burgess E, Lewanczuk R, Dresser GK, Penner SB, Hegele RA, McFarlane PA, Sharma M, Reid DJ, Tobe SW, Poirier L, Padwal RS; Canadian Hypertension Education Program. The 2013 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Can J Cardiol 2013 May;29(5):528-542.

? Gros R, Ding Q, Liu B, Chorazyczewski J, Feldman RD. Aldosterone mediates its rapid effects in vascular endothelial cells GPER/GPR30 activation. Am?J Physiol Cell Physiol 2013 Mar;304(6):C532-540.

? Ostrom RS, Bogard AS, Gros R, Feldman RD. Choreographing the adenylyl cyclase signalosome: sorting out the partners and the steps. Naunyn-Schmiedeberg's Arch Pharmacol 2012 Jan;385(1):5–12.

? Feldman RD. ACP Journal Club. Review: Home and clinic BP have limited accuracy compared with ambulatory BP for diagnosing hypertension. Ann Intern Med 2011 Dec;155(12):JC6-10.

? Feng B, Chen S, McArthur K, Wu, Y, Sen S, Ding, Q, Feldman RD, Chakrabarti S. miR-146a mediated extracellular matrix protein production in chronic diabetic complications. Diabetes 2011 Nov;60(11):2975-2984.

? Gros R, Ding QM, Davis M, Shaikh R, Chorazyczewski J, Pickering JG, Feldman RD. Delineating the receptor mechanisms underlying the rapid vascular contractile effects of aldosterone and estradiol. Can J Physiol Pharmacol 2011 Sep;89(9)665-663.

? Rabi DM, Daskalopoulou SS, Padwal RS, Khan NA, Grover SA, Hackam DG, Myers MG, McKay DW, Quinn RR, Hemmelgarn BR, Cloutier L, Bolli P, Hill MD, Wilson T, Penner B, Burgess E, Lamarre-Cliché M, McLean D, Schiffrin EL, Honos G, Mann K, Tremblay G, Milot A, Chockalingam A, Rabkin SW, Dawes M, Touyz RM, Burns KD, Ruzicka M, Campbell NR, Vallée M, Prasad GV, Lebel M, Campbell TS, Lindsay MP, Herman RJ, Larochelle P, Feldman RD, Arnold JM, Moe GW, Howlett JG, Trudeau L, Bacon SL, Petrella RJ, Lewanczuk R, Stone JA, Drouin D, Boulanger JM, Sharma M, Hamet P, Fodor G, Dresser GK, Carruthers SG, Pylypchuk G, Gilbert RE, Leiter LA, Jones C, Ogilvie RI, Woo V, McFarlane PA, Hegele RA, Poirier L, Tobe SW; Canadian Hypertension Education Program. The 2011 Canadian hypertension education program recommendations for the management of hypertension: blood pressure measurement, diagnosis, assessment of risk, and therapy. Can J Cardiol 2011 Jul-Aug;27(4):415-433.e2.

? Feldman RD and Gros R. Unraveling the mechanisms underlying the rapid vascular effects of steroids: sorting out the receptors and the pathways. British Journal of Pharmacology 2011 Jul;163(6):1163–1169.

? Gros R, Ding QM, Sklar LA, Prossnitz EE, Arterburn JB, Chorazyczewski J and Feldman RD. GPR30 expression is required for the mineralocorticoid receptor-independent rapid vascular effects of aldosterone. Hypertension 2011 Mar;57(3):442-451.

? Nelson SAE, Dresser G, Vandervoort MK, Wong C, Feagan BG, Mahon JL, Feldman RD. Barriers to blood pressure control: A STITCH substudy. J Clin Hyperten 2011 Feb;13:73-80.

? Hodges GJ, Gros R, Hegele MD, Van Uum S, Shoemaker JK, Feldman RD. Increased blood pressure and hyperdynamic cardiovascular responses in carriers of a common hyperfunctional variant of adenylyl cyclase 6. J Pharmacol Exp Ther 2010 Nov;335(2):451-457.

? Dresser GK, Feldman RD. New trends in hypertension management: of salt, going solo and single pill combos. Curr Opin Cardiol 2010 Jul;25(4):342-349.

? Hackam DG, Khan NA, Hemmelgarn BR, Rabkin SW, Touyz RM, Campbell NR, Padwal R, Campbell TS, Lindsay MP, Hill MD, Quinn RR, Mahon JL, Herman RJ, Schiffrin EL, Ruzicka M, Larochelle P, Feldman RD, Lebel M, Poirier L, Arnold JM, Moe GW, Howlett JG, Trudeau L, Bacon SL, Petrella RJ, Milot A, Stone JA, Drouin D, Boulanger JM, Sharma M, Hamet P, Fodor G, Dresser GK, Carruthers SG, Pylypchuk G, Burgess ED, Burns KD, Vallée M, Prasad GV, Gilbert RE, Leiter LA, Jones C, Ogilvie RI, Woo V, McFarlane PA, Hegele RA, Tobe SW; Canadian Hypertension Education Program. The 2010 Canadian Hypertension Education Program recommendations for the management of hypertension: Part 2--therapy. Can J Cardiol 2010 May;26(5):249-258.

?Gros R, Feldman RD. Rapid Vascular Effects of Steroids: a question of balance?" The Canadian Journal of Cardiology. 2010; 26 Suppl A:22A-26A.

Contact Info

Ross D. Feldman, MD
RW Gunton Professor of Therapeutics
Departments of Medicine and of Physiology & Pharmacology
University of Western Ontario

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Scientist, Molecular Medicine: Vascular and Brain Health Group
Robarts Research Institute
1151 Richmond St. N.
London, ON, Canada
N6A 5B7
Phone: 519-931-5717
Fax:????? 519-931-5789

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