Prof. Jacques Genest

Professor of Medicine, Director, Center for Innovative Medicine

The research program we have undertaken for the past two decades is centered on the genetic basis for premature coronary artery disease, focusing on lipoprotein disorders, especially high-density lipoproteins (HDL). My training is that of a cardiologist, with a post-doctoral fellowship in lipoprotein metabolism and molecular genetics. Through extensive family studies, we have identified several genes associated with HDL, including the ATP binding cassette AI (ABCA1) the cause of Tangier disease and the rate-limiting step in HDL formation. For the past 10 years, we have focused on the mechanisms of HDL biogenesis and the environment created on the cell membrane through the ABCA1 transporter. The second major focus of our laboratory has been the study of the genetics of HDL. We have used the combined approaches of carefully phenotyped family studies, with bioinformatics data from genome-wide association studies. A third area of interest is the study of autosomal dominant hypercholesterolemia and premature vascular calcifications.

1. Ridker PM, MacFadyen JG, Fonseca FAH, Genest J, Gotto MA, Kastelein JJP, Koenig W, Libby P, Lorenzatti AJ, Nordestgaard BG, Shepherd J, Willerson T, Glynn RJ for the JUPITER Study Group.  Number Needed To Treat with Rosuvastatin to Prevent Cardiovascular Events and Death Among Men and Women with Low LDL Cholesterol and Elevated hsCRP: The JUPITER Trial. In press, Circulation: Cardiovasc Quality Outcomes 2009;2(6):816-823
2. Bailey D, Jahagirdar R, Gordon A, Hafiane A, Campbell S, Shatur S, Wagner GS, Hansen HC, Chiacchia FS, Johansson J, Krimbou L, Wong NCW, Genest J. RVX-208: A Small Molecule That Increases Apolipoprotein A-I and High-Density Lipoprotein Cholesterol In Vitro and In Vivo. J Am Coll Cardiol 2010 55: 2580-2589.
3. Mora S, Glynn RJ, Hsia J, Macfadyen JG, Genest J, Ridker PM. Statins for the Primary Prevention of Cardiovascular Events in Women With Elevated High-Sensitivity C-Reactive Protein or Dyslipidemia. Results From the Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) and Meta-Analysis of Women From Primary Prevention Trials. Circulation. 2010 Mar 9;121(9):1069-77.
4. Ridker P, Genest J, Boekholdt SM, Libby P, Gotto , Brno, Mora S, MacFadyen J, Glynn R, Kastelein JJ. High Density Lipoprotein Cholesterol and Risk of First Cardiovascular Events After Treatment with Potent Statin Therapy. Lancet. 2010 Jul 31;376:333-9
5. Ridker PM, MacFadyen J, Nordestgaard BG, Koenig W, Kastelein JL, Genest J, Glynn RJ. Rosuvastatin for Primary Prevention Among Individuals with Elevated hsCRP and 5 to 10 and 10 to 20 Percent 10-Year Risk: Implications of the Justification for Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) Trial for “Intermediate Risk”. Accepted Circulation: Cardiovascular Outcomes and Quality Jun 2010
6. Awan Z, Alwaili K, AlShaharani A, Goltzman D, Genest J. Calcium Homeostasis and Cortical Bone Integrity in Aortic Calcification in Subjects with Familial Hypercholesterolemia [*] Clin Chem. 2010;56(10):1599-607
7. Roifman I, Beck P, Anderson TJ, Eisenberg M, Genest J. Chronic inflammatory diseases and cardiovascular risk. [*] Can J cardiol 2011;27;174-182
8. Leiter LA, Fitchett D, Gilbert RE, M Gupta, Mancini JBJ, McFarlane PA, Ross R, Teoh H, Verma S (Executive Committee), Working Group: Anand S, Camelon K,  Chow C-M, Cox JL, Després JP,
9. Mancini JGB, Baker S, Bergeron J, Frohlich J, Fitchett D, Genest J, Gupta M, Hegele RA, Ng D, Pope J. Diagnosis, prevention, and management of statin adverse effects and intolerance: proceedings of a Canadian Working Group Consensus Conference. Can J cardiol 2011;27:635-662
10. Iatan I, Bailey D, Ruel I, Hafiane A, Krimbou L, Genest J. Membrane microdomains modulate oligomeric ABCA1 function: impact on apoAI-mediated lipid removal and phosphatidylcholine biosynthesis. J Lipid Res. 2011;52(11):2043-55.
11. Awan Z, Denis M, Bailey D, Giaid A, Prat A, Goltzman D, Seidah NG, Genest J. The LDL-R Deficient Mouse as a Model for Aortic Calcification and Quantify by micro computer tomography. Atheroscler 2011;219:455-62 published online
12. Tobe SW, Stone JA, Brouwers M, Battacharyya O, Walker KM, Dawes M, Genest J, Grover S, Gubitz G, Lau D, Popo A, Selby P, Tremblay MS, Warburton DER, Ward R, Woo V, Leiter LA, Liu PP. Harmonization of guidelines for the prevention and treatment of cardiovascular disease: the C-CHANGE initiative. CMAJ 2011;183:e113-50 on line pub. Sept 12, 2011
13. Alwaili K*, Bailey D*, Awan Z, Laboissiere S, Krimbou L, Genest J. The HDL proteome in acute coronary syndromes shifts to an inflammatory phenotype. [CIHR MOP 15042]  [*] BBA - Molecular and Cell Biology of Lipids Biochim Biophys Acta. 2012 Mar;1821(3):405-15
14. Awan Z, Danielson E, Glyn R, Ridker PM, Seidah NG, Genest J. Rosuvastatin, PCSK9 Levels, and LDL-C Response: The JUPITER Trial. Clin Chem. 2012 Jan;58(1):183-9. Epub 2011 Nov 7.Editorial. [*]CIHR CTP 82946
15. Lee C-Y, Ruel I, Denis M, Genest J, Kiss RS. Cholesterol trapping in the endosomal pathway does not impair cholesterol efflux in Niemann-Pick disease type B fibroblasts. [CIHR MOP 15042; CIHR 97752 and HSFC]  [*]. J Clin Lipidol Accepted 02.1012
16. Linga Reddy MVP* Iatan I*, Weissglas-Volkov D, Nokkola E, Haas B, Sinsheimer J, Genest J, Pajukanta P. Exome sequencing identifies two rare variants for low HDL-C in an extended family. Accepted: Circulation Cardiovasc Genet Jul 2012 
17. Fantus D. Awan Z, Seidah N, Genest J. Aortic Calcifications: Novel Insights from Familial Hypercholesterolemia and Potential Role for the Low-Density Lipoprotein Receptor. Atheroscler 2012