Robarts Research

Why I Became a Scientist

As a clinician, I remain driven by the opportunity to develop new therapeutic approaches for the treatment of chronic vascular disease.  It is that opportunity that brought me back to the lab following from my clinical training.  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 o 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 (Am J Physiol Cell Physiol; 2009 Nov;297(5):C1178-87) .

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 (Hypertension 2009:53:646-653).

Research Questions and Disease Implications

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

Estrogen has been shown to be both cardioprotective and to precipitate CV 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 does regulation of adenylyl cyclase impact on cardiovascular regulation/cardiovascular disease?

Adenylyl cyclase is a master regulator of CV cell function.   We have recently found that expression of genetic variants of this enzyme leads to higher blood pressure.  Understanding how this enzyme is regulated may be critical to our understanding of the mechanisms and complications of high blood pressure.

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

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

• 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) 385:5–12

•Feldman RD. ACP Journal Club. Review: Home and clinic BP have limited accuracy compared with ambulatory BP for diagnosing hypertension. Ann Intern Med. 2011;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. 2011:60(11):2975-84.

•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 2011:89(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;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;163: 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;57(3):442-51.

•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;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; 335(2):451-7.

•Dresser, GK, Feldman RD. New trends in hypertension management: of salt, going solo and single pill combos. Curr Opin Cardiol. 2010;25(4):342-9.

•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;26(5):249-58.

•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 Information

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

 

Scientist, Vascular Biology Group
Robarts Research Institute
100 Perth Dr
London, ON, Canada
N6A 5K8
Phone: 519-931-5717
Fax:      519-931-5222

www.robarts.ca