Dr. Ross Feldman
Women’s Health, Institute of Cardiovascular Sciences
Professor of Medicine
Medical Director, Cardiac Sciences Program, WRHA
Heart disease in women remains underappreciated, underdiagnosed and undertreated. Further, although we are starting to understand some of the social and behavioral determinants for this, the biological basis for the increased rate of rise in atherosclerosis risk in women after menopause remains very poorly understood. We continue to explore the biological basis underlying the increased prevalence of atherosclerotic risk factors in postmenopausal women (vs. men) and the role of the G protein-coupled estrogen receptor (GPER) and its genetic regulation as a determinant of these sex-specific risks. GPER is a recently appreciated GPCR that mediates the rapid effects of estrogen and aldosterone. Recent studies have identified that GPER activation regulates both blood pressure. We have shown that regulation of GPER function via expression of a hypofunctional GPER genetic variant is an important determinant of blood pressure and risk of hypertension in women. Further, our most recent studies have identified that GPER activation is an important regulator of low density lipoprotein receptor metabolism and that expression of the hypofunctional GPER genetic variant is an important contributor to the development of hypercholesterolemia in women. GPER appears to be an important determinant of the two major risk factors for coronary artery disease-blood pressure and LDL cholesterol. Further, the importance of this mechanism appears to be greater in women. The appreciation of the role of GPER function as a determinant of the progression of atherosclerotic disease may be important both in our understanding of cardiometabolic function but also in opening the way to greater appreciation of the sex-specific regulation of atherosclerotic risk factors.
A second area of research relates to the role of aldosterone in regulating the spread of cancers. Aldosterone, is best known as a hormone regulating salt and water balance in the body. However, based on our discovery that aldosterone acts in part via regulation of GPER0- a receptor implicated in regulation of the extent of spread of a number of cancers, we began to explore the potential role of aldosterone in the regulation of cancer spread. Our initial studies demonstrated the importance of aldosterone in regulating the spread of kidney cancer. Our ongoing studies examine the importance of aldosterone regulation as a generalized mechanism in controlling cancer spread. If established, these studies will help propel the development of novel adjunctive therapies for the treatment of hard to control cancers.
What techniques and equipment are used in this laboratory?
The techniques we use span the range from molecular to cellular to integrative physiology. We develop constructs to manipulate genetic expression of a range of receptors and assess the impact of these manipulations in cell communication using immunoblotting an enzymatic assays and measures of cell growth and death. Additionally we assess the impact of these manipulations on blood vessel function—especially after blood vessel injury.
About Dr. Ross Feldman
• Queen’s University, University of Toronto, Vanderbilt University
• BSc, MD, Internal Medicine residency, Post-doctoral training in Clinical Pharmacology
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Dr. Ross Feldman
Publications from 2014
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.
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.
Ferguson SSG, Feldman RD. Beta adrenoceptors as molecular targets in the treatment of hypertension. Can J Cardiol 2014 May;30(5 Suppl): S3-8.
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, Lamarre-Cliché M, Tremblay G, Hamet P, Fodor 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 pressure measurement, diagnosis, assessment of risk, prevention and treatment of hypertension. Can J Cardiol 2014 May;30(5):485-501.
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.
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, 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.
Ding Q, Hussain Y, Chorazyczewski J, Gros R, Feldman RD. GPER-independent effects of estrogen in rat aortic vascular endothelial cells. Mol Cell Endocrinol 2015; 399:60-68.
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.
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.
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 review of current recommendations. Drugs 2014 Nov;74 (17):2033-2051.
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.
Feldman RD, Anderson TJ, Touyz RM. Metabolic syndrome sinkholes: what to do when Occam’s razor gets blunted. Can J Cardiol 2015 May; 31:601-604.
Stella S Daskalopoulou, Doreen M Rabi, Kelly B Zarnke, Kaberi Dasgupta, Kara Nerenberg, Lyne Cloutier, Mark Gelfer, Maxime Lamarre-Cliche, Alain Milot, Peter Bolli, Donald W McKay, Guy Tremblay, Donna McLean, Sheldon W Tobe, Marcel Ruzicka, Kevin D Burns, Michel Vallée, GV Ramesh Prasad, Marcel Lebel, Ross D Feldman, Peter Selby, Andrew Pipe, Ernesto L Schiffrin, Philip A McFarlane, Paul Oh, Robert A Hegele, Milan Khara, Thomas W Wilson, S Brian Penner, Ellen Burgess, Robert J Herman, Simon L Bacon, Simon W Rabkin, Richard E Gilbert, Tavis S Campbell, Steven Grover, George Honos, Patrice Lindsay, Michael D Hill, Shelagh B Coutts, Gord Gubitz, Norman RC Campbell, Gordon W Moe, Jonathan G Howlett, Jean-Martin Boulanger, Ally Prebtani, Pierre Larochelle, Lawrence A Leiter, Charlotte Jones, Richard I Ogilvie, Vincent Woo, Janusz Kaczorowski, Luc Trudeau, Robert J Petrella, Swapnil Hiremath, James A Stone, Denis Drouin, Kim L Lavoie, Pavel Hamet, George Fodor, Jean C Grégoire, Anne Fournier, Richard Lewanczuk, George K Dresser, Mukul Sharma, Debra Reid, Geneviève Benoit, Janusz Feber, Kevin C Harris, Luc Poirier, Raj S Padwal, Canadian Hypertension Education Program. The 2015 Canadian Hypertension Education Program Recommendations for Blood Pressure Measurement, Diagnosis, Assessment of Risk, Prevention, and Treatment of Hypertension. Can J Cardiol 2015 May; 31:549-568.
Feldman RD, Limbird LE. Copernicus revisited: Overturning Ptolemy’s view of the GPER universe. Trends in Endocrinology and Metabolism 2015; 26:592-594
Dasgupta K, Padwal R, Poirier L, Quinn RR; Canadian Hypertension Education Program Scientific Summary Writing Group, Bacon S, Feldman RD, Hackam DG, Herman RJ, Khan N, Rabi DM, Ravani P, Tobe S, Rabkin S, Trudeau L, Zarnke K. Managing hypertension: evidence supporting the 2013/2014 recommendations of the Canadian Hypertension Education Program. CMAJ 2015; 187:116-119.
Campbell NRC, Feldman RD. Hypertension in Canada and the global context: the wine is vintage and the glass is two thirds full but is the bottle empty? Can J Cardiol 2016; 32: 609
Feldman RD, Padwal RS. Are we endangering hypertensive patients by overzealous treatment that induces diastolic hypotension? A SPRINT to the answer? Can J Cardiol 2016; 32:607-608
Feldman RD, Ding Q, Hussain Y, Limbird LE, Pickering JG, Gros R. Aldosterone mediates metastatic spread of renal cancer via the G protein–coupled estrogen receptor (GPER). FASEB J. 2016; 30:2086-2096
Feldman RD, Harris SB, Hegele RA, Pickering JG, Rockwood K. Applying Atherosclerotic Risk Prevention Guidelines to Elderly Patients: A Bridge Too Far? Can J Cardiol. 2016; 32:598-602.
Leung AA, Nerenberg K, Daskalopoulou SS, McBrien K, Zarnke KB, Dasgupta K, Cloutier L, Gelfer M, Lamarre-Cliche M, Milot A, Bolli P, Tremblay G, McLean D, Tobe SW, Ruzicka M, Burns KD, Vallée M, Prasad GV, Lebel M, Feldman RD, Selby P, Pipe A, Schiffrin EL, McFarlane PA, Oh P, Hegele RA, Khara M, Wilson TW, Penner SB, Burgess E, Herman RJ, Bacon SL, Rabkin SW, Gilbert RE, Campbell TS, Grover S, Honos G, Lindsay P, Hill MD, Coutts SB, Gubitz G, Campbell NR, Moe GW, Howlett JG, Boulanger JM, Prebtani A, Larochelle P, Leiter LA, Jones C, Ogilvie RI, Woo V, Kaczorowski J, Trudeau L, Petrella RJ, Hiremath S, Drouin D, Lavoie KL, Hamet P, Fodor G, Grégoire JC, Lewanczuk R, Dresser GK, Sharma M, Reid D, Lear SA, Moullec G, Gupta M, Magee LA, Logan AG, Harris KC, Dionne J, Fournier A, Benoit G, Feber J, Poirier L, Padwal RS, Rabi DM; CHEP Guidelines Task Force. Hypertension Canada’s 2016 Canadian Hypertension Education Program Guidelines for Blood Pressure Measurement, Diagnosis, Assessment of Risk, Prevention, and Treatment of Hypertension. Can J Cardiol. 2016; 32:569-88.
Feldman RD. Heart Disease in Women: Unappreciated Challenges, GPER as a New Target. Int. J. Mol. Sci. 2016, 17, 760; doi:10.3390/ijms17050760.
Schiffrin EL, Campbell RC, Feldman RD, Kaczorowski J, Lewanczuk R, Padwal R, Tobe SW. Hypertension in Canada: Past, Present, and Future. Annals of Global Health. 2016; 82:288-299.
Gros R, Hussain Y, Chorazyczewski J, Pickering JG, Ding Q and Feldman RD. The extent of vascular remodelling is dependent on the balance between ERα and GPER. Hypertension 2016; 68:1225-1235
Feldman RD, Limbird LE. GPER: A nongenomic receptor (GPCR) for steroid hormones with implications for cardiovascular disease and cancer. Ann Rev Pharmacol. Toxicol 2017.57:567-584.
Feldman RD, Padwal R. Application of Hypertension Guidelines in the Elderly. Revisiting where The Bridge to Nowhere may actually be going. Can J Cardiol. 2017; 33:591-593
Pollak PT, Herman RJ, Feldman RD. Therapeutic Differences in 24-h Ambulatory Blood Pressures in Patients Switched Between Bioequivalent Nifedipine Osmotic Systems With Differing Delivery Technologies. Clin Transl Sci. 2017; 10:217-224
Feldman RD, Liu L, Wu Z, Zhang Y, Yu X, Zhang X-H. Hypertension Attitude PersPEctives and Needs (HAPPEN): a real-world survey of physicians and patients with hypertension in China. J. Clin. Hypertension 2017; 19:256-264.
Alexander A Leung, Stella S Daskalopoulou, Kaberi Dasgupta, Kerry McBrien, Sonia Butalia, Kelly B Zarnke, Kara Nerenberg, Kevin C Harris, Meranda Nakhla, Lyne Cloutier, Mark Gelfer, Maxime Lamarre-Cliche, Alain Milot, Peter Bolli, Guy Tremblay, Donna McLean, Sheldon W Tobe, Marcel Ruzicka, Kevin D Burns, Michel Vallée, GV Ramesh Prasad, Steven E Gryn, Ross D Feldman, Peter Selby, Andrew Pipe, Ernesto L Schiffrin, Philip A McFarlane, Paul Oh, Robert A Hegele, Milan Khara, Thomas W Wilson, S Brian Penner, Ellen Burgess, Praveena Sivapalan, Robert J Herman, Simon L Bacon, Simon W Rabkin, Richard E Gilbert, Tavis S Campbell, Steven Grover, George Honos, Patrice Lindsay, Michael D Hill, Shelagh B Coutts, Gord Gubitz, Norman RC Campbell, Gordon W Moe, Jonathan G Howlett, Jean-Martin Boulanger, Ally Prebtani, Gregory Kline, Lawrence A Leiter, Charlotte Jones, Anne Marie Côté, Vincent Woo, Janusz Kaczorowski, Luc Trudeau, Ross T Tsuyuki, Swapnil Hiremath, Denis Drouin, Kim L Lavoie, Pavel Hamet, Jean C Grégoire, Richard Lewanczuk, George K Dresser, Mukul Sharma, Debra Reid, Scott A Lear, Gregory Moullec, Milan Gupta, Laura A Magee, Alexander G Logan, Janis Dionne, Anne Fournier, Geneviève Benoit, Janusz Feber, Luc Poirier, Raj S Padwal, Doreen M Rabi, Hypertension Canada. Hypertension Canada’s 2017 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults. Can J Cardiol. 2017; 33:557-576
- 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
- Heart and Stroke Foundation