Rob Hegele, Scientist
Why I Became a Scientist
From my parents, I developed at an early age a great appreciation for academics and learning. I attended the University of Toronto and received my medical degree in 1981. Specialty training in Internal Medicine and Endocrinology was followed by four years of post-doctoral training, first at the Rockefeller University, New York City, in heart disease and cholesterol, and then in human genetics at the Howard Hughes Medical Institute in Salt Lake City, Utah. It was during my research fellowship in New York City that I became inspired to pursue research in genetics. With a strong belief in the power of human genetics and genomics to help solve fundamental problems related to human health and disease, my lab began researching the genetic basis of several human disorders, most notably several forms of dyslipidemia (high cholesterol) and type 2 diabetes.
Research Summary
Rob Hegele is an endocrinologist with an interest in lipidology and diabetes, who cares for >1700 patients. He is the Director of the Blackburn Cardiovascular Genetics Lab and London Regional Genomics Centre. He has trained many physicians in lipidology and several graduate students in human genetics. His laboratory has studied the genetic basis of diabetes and atherosclerosis in Canadian sub-populations and aboriginal communities. His lab discovered the molecular genetic basis of 12 human diseases, including hepatic lipase deficiency, Oji-Cree type 2 diabetes, familial partial lipodystrophy and endocrine-cerebro-ostedysplasia and has described >100 human mutations causing dyslipidemia, diabetes and atherosclerosis. He has published >500 original peer-reviewed articles and serves on numerous journal editorial boards, including Journal of Clinical Investigation, Circulation, Stroke, ATVB and Journal of Lipid Research. He has received numerous international awards recognizing his research and is listed among the top 1% of highly cited scientists in all disciplines.
Research Questions and Disease Implications
Why do some individuals and families develop heart disease and stroke despite very clean living and healthy lifestyles?
Identification of new genes that can cause heart disease, stroke and such high risk conditions as diabetes, hyperlipidemia and hypertension.
Identification of new genes leads to new understanding of pathways for these diseases and is the first step in the development of new diagnostic methods and treatments.
Why are certain aboriginal groups in Canada so highly predisposed to developing diabetes?
Identification of new genes and the exacerbating environmental factors that cause diabetes can lead to new understanding of the underlying pathways and is the first step in the development of new diagnostic methods and treatments.
How is it that certain people can eat as much as they like and not gain any weight, while some others eat sparingly but cannot seem to lose weight?
Identification of new genes that create susceptibility to obesity can lead to new understanding of the underlying pathways and is the first step in the development of new diagnostic methods and treatments.
Education
• 1975 Associate (Honours), Royal Conservatory of Music of Toronto
• 1981 MD (Honours), University of Toronto
Training
• 1985 FRCP(C), Internal Medicine
• 1987 FRCP(C), Subspecialty certification, Endocrinology & Metabolism
• 1985- 87 Research Associate, Biochemical Genetics & Metabolism,
• Rockefeller University, New York, New York
• 1987-89 Research Associate, Human Genetics, Howard Hughes Medical Institute, Salt Lake City, Utah
• 1991 FACP, Internal Medicine
• 2004 FAHA
• 2007 FCAHS
Awards
• 1995 Young Investigator Award, American Federation for Clinical Research
• 2000 Canada Research Chair in Human Genetics, Tier I
• 2001 Elected to membership, American Society for Clinical Investigation
• 2001 American Heart Association Top Ten Scientific Discoveries for 2001
• 2001 Government of Ontario Distinguished Researcher Award
• 2001 Faculty of Medicine and Dentistry Award of Excellence, UWO
• 2002 Canadian Diabetes Association Young Scientist Award
• 2004 Edith Schulich Vinet Canada Research Chair in Human Genetics, Tier I
• 2004 Hellmuth Prize for Achievement in Research, UWO
• 2004 American Heart Association, Jeffrey M. Hoeg Award for Basic Science
& Clinical Research, Arteriosclerosis, Thrombosis & Vascular Biology Council
• 2005 35th Charles H. Best Lecture Award, Toronto Diabetes Association
• 2005 Jacob J. Wolfe Distinguished Medical Research Chair in Human Gene Function
• 2006 William F. Grant and Peter B. Moens Award of Excellence,
• Genetics Society of Canada
• 2007 Distinguished University Professor Award, UWO
• 2007 Elected to Fellowship in the Canadian Academy of Health Sciences
• 2007 American Heart Association, Special Recognition Award in Arteriosclerosis, Scientific Council on Arteriosclerosis, Thrombosis and Vascular Biology
• 2007 Jean Davignon Distinguished Cardiovascular Metabolic Research Award
• 2009 Department of Medicine Research Award of Excellence, U.W.O.
Publications
Hegele RA, Cao H, Liu DM, Costain GA, Charlton-Menys V, Rodger NW, Durrington PN. Sequencing of the reannotated LMNB2 gene gene reveals novel mutations in patients with acquired partial lipodystrophy. Am J Hum Genet 2006; 79:383-389. (PMID: 16826530)
Edmondson AC, Brown RJ, Kathiresan S, Cupples LA, Demissie S, Manning AK, Jensen MK, Rimm EB, Wang J, Rodrigues A, Bamba V, Khetarpal SA, Wolfe ML, Derohannessian S, Li M, Reilly MP, Aberle J, Evans D, Hegele RA, Rader DJ. Loss-of-function variants in endothelial lipase are a cause of elevated HDL cholesterol in humans. J Clin Invest 2009; 119:1042-1050. (PMID: 19287092)
Zeissig S, Dougan SK, Barral DC, Junker Y, Chen Z, Kaser A, Ho M, Mandel H, McIntyre A, Kennedy SM, Painter GF, Veerapen N, Besra GS, Cerundolo V, Yue S, Beladi S, Behar SM, Chen X, Gumperz JE, Breckpot K, Raper A, Baer A, Exley MA, Hegele RA, Cuchel M, Rader DJ, Davidson NO, Blumberg RS. Primary deficiency of microsommal triglyceride transfer protein in human abetalipoproteinemia is associated with loss of CD1 function. J Clin Invest 2010; 120:2889-2899. (PMID: 20592474)
Johansen CT, Wang J, Lanktree MB , Cao H, McIntyre AD, Ban MR, Martins RA, Kennedy BA, Hassell RG, Visser ME, Schwartz SM, Voight BF, Elosua R, Salomaa V, O’Donnell CJ, Dallinga-Thie GM, Anand SS, Yusuf S, Huff MW, Kathiresan S, Hegele RA. Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia. Nature Genet 2010; 42:684-687. (PMID: 20657596)
Teslovich TM, Musunuru K, (+ additional 157 authors) Hegele RA, Kastelein JJ, Schadt EE, Rotter JI, Boerwinkle E, Strachan DP, Mooser V, Stefansson K, Reilly MP, Samani NJ, Schunkert H, Cupples LA, Sandhu MS, Ridker PM, Rader DJ, van Duijn CM, Peltonen L, Abecasis GR, Boehnke M, Kathiresan S. Biological, clinical and population relevance of 95 loci for blood lipids. Nature 2010; 466:707-713. (PMID: 20686565)
Li Y, Laue K, Temtamy S, Aglan M, Kotan LD, Yigit G, Canan H, Pawlik B, Nürnberg G, Wakeling EL, Quarrell OW, Baessmann I, Lanktree MB, Yilmaz M, Hegele RA, Amr K, May KW, Nürnberg P, Topaloglu AK, Hammerschmidt M, Wollnik B. Temtamy preaxial brachydactyly syndrome is caused by loss-of-function mutations in chondroitin synthase 1, a potential target of BMP signaling. Am J Hum Genet 2010; 87:757-767. (PMID: 21129728)
Lanktree MB, Guo Y, (+ additional 142 authors) Hegele RA, Hakonarson H, Keating BJ. Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height. Am J Hum Genet 2011; 88:6-18. (PMID: 21194676)
Johansen CT, Wang J, Hegele RA. Bias due to selection of rare variants using frequency in controls. Nature Genet 2011; 43:394-395. (PMID: 21522174)
Daar AS, Scherer SW, Hegele RA. Implications of copy – number variation in the human genome: a time for questions. Nature Rev Genetics 2006; 7: 414.
Pollex RL, Hegele RA. Genetic determinants of plasma lipoproteins. Nature Clin Pract Cardiovasc Med 2007; 4:600-609. (PMID: 17957207)
Oh J, Hegele RA. HIV-associated dyslipidaemia: pathogenesis and treatment. Lancet Infect Dis. 2007; 7:787-796. (PMID: 18045561)
Joy T, Hegele RA. Is raising HDL a futile strategy for atheroprotection? Nature Rev Drug Discov 2008; 7:143-155. (PMID: 18239670)
Hegele RA. Plasma lipoproteins: genetic influences and clinical implications. Nature Rev Genetics 2009; 10:109-121. (PMID: 19139765)
Hegele RA, Reue K. Hoofbeats, zebras, and insights into insulin resistance. J Clin Invest 2009; 119:249-251. (PMID: 19244606)
Joy TR, Hegele RA. Narrative review: Statin-related myopathy. Ann Intern Med 2009; 150:858-868. (PMID: 19528564)
Lahiry P, Torkamani A, Schork N, Hegele RA. Kinase mutations in human disease: Interpreting genotype-phenotype relationships. Nature Rev Genetics 2010; 11:60-74. (PMID: 20019687)
Contact Information
Robarts Research Institute
Room 4288A, 100 Perth Drive
London, ON N6A 5K8
Assistant: Ericka Simon
Tel: 519-931-5774; Fax: 519 931-5218
E-mail: esimon@robarts.ca
www.robarts.ca/hegele * www.lipidgeneticsclinic.ca