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Senior Scientist, Chronic Disease
, Ottawa Health Research
Institute
Associate Professor (Department of Biochemistry, Microbiology & Immunology, Faculty of Medicine, Univ. of Ottawa; Division of Endocrinology, The Ottawa Hospital)
Health Research Interests
Obesity and Diabetes
Major Research Activities
Our laboratory is interested in elucidating the roles of proprotein convertases subtilisin/kexin types (PCSKs) in body mass, glucose and lipid homeostasis. The following projects are currently being pursued.
1. Gastrointestinal functions of PCSK1- and PCSK2. PCSK1 and PCSK2 are expressed in the gastrointestinal tract (GIT), including the pancreas, where they mediate the production of a number of hormones. Our previous studies have shown that heritable deficiency of PCSK1 or PCSK2 in mice results in susceptibility or resistance to diet-induced obesity, respectively. This project examines how these deficiencies affect intestinal and pancreatic functions: i.e. food intestinal transit, food absorption, calorie utilization and storage, and ultimately body mass and glucose homeostasis. The prohormone processing defects in the GIT are also characterized to better explain the observed phenotype.
2. Protective roles of PCSK9 in extrahepatic tissues. PCSK9 is primarily expressed and secreted by the liver. It is known to down regulate receptor-mediated hepatic uptake of plasma low-density lipoprotein cholesterol (LDL-c). PCSK9 is also expressed in several extrahepatic tissues including the kidney, the pancreas and adipose tissues. In the pancreas, it is exclusively found in insulin-producing beta cells. We have hypothesized that its role in these cells is to protect against excessive uptake of exogenous cholesterol. LDL-c accumulation in pancreatic beta cells impairs glucose-induced hormone secretion by these cells, causes their apoptosis and leads to diabetes. Using insulinoma cell lines, pancreatic islets and PCSK9-deficient mice, the project explores the roles of PCSK9 in pancreatic beta cell survival and functions as well as in glucose homeostasis.
3. Association of nonsense PCSK9 mutations with resistance to infection. Nonsense PCSK9 mutations have been associated with lifelong hypocholesterolemia and near complete protection against coronary heart disease (CAD). We have proposed that the high frequency of these mutations in some populations could be due to positive selection during evolution. We postulate that chronic hypocholesterolemia caused by loss of PCSK9 function reduces the risk of early mortality from infectious (parasitic and viral) diseases. Many infectious agents are known to require host cholesterol for infectivity. This project explores possible association of nonsense PCSK9 mutations with resistance to infectious diseases in exposed populations.
Major Awards
Québec Science Magazine
10 Most Significant Discovery of 1997, 1998.
Fellow of the Fonds de Recherches en Santé du Québec (sabbatical fellowship),
1993-1994).
Fellow of the Government of Quebec, 1982 - 1983.
Graduate Studentship of the African-American Institute (USA), 1973 - 1978.
Pharmacy Diploma, Magna cum Laude, 1971
SPECIA Laureate (Société Parisienne d'Expansion Chimique et Industrielle)
for academic excellence. 1971.
Most Recent Publications (provided by The Ottawa Hospital Library Database)
Gyamera-Acheampong C;Vasilescu J;Figeys D;Mbikay M;, (2009 Mar 31), PCSK4-null sperm display enhanced protein tyrosine phosphorylation and ADAM2 proteolytic processing during in vitro capacitation, Fertil Steril, -> view abstract
Gyamera-Acheampong C;Mbikay M;, (2009 Mar), Proprotein convertase subtilisin/kexin type 4 in mammalian fertility: a review. [Review] [117 refs], Human Reproduction Update, Vol.15, Issue 2, 237-247 -> view abstract
Wang Y;Gao E;Wu J;Zhou J;Yang Q;Walker MC;Mbikay M;Sigal RJ;Nair RC;Wen SW;, (2009 Jun 30), Fetal macrosomia and adolescence obesity: results from a longitudinal cohort study, Int J Obes (Lond), Vol.33, Issue 8, 923-928 -> view abstract
Mbikay M;Sirois F;Mayne J;Wang GS;Chen A;Dewpura T;Prat A;Seidah NG;Chretien M;Scott FW;, (2009 Dec 16), PCSK9-deficient mice exhibit impaired glucose tolerance and pancreatic islet abnormalities, FEBS Lett , -> view abstract
Gagnon J;Mayne J;Mbikay M;Woulfe J;Chretien M;, (2009), Expression of PCSK1 (PC1/3), PCSK2 (PC2) and PCSK3 (furin) in mouse small intestine, Regulatory Peptides, Vol.152, Issue 3-Jan, 54-60 -> view abstract
Sirois F;Gbeha E;Sanni A;Chretien M;Labuda D;Mbikay M;, (2008 Sep), Ethnic differences in the frequency of the cardioprotective C679X PCSK9 mutation in a West African population, Genetic Testing, Vol.12, Issue 3, 377-380 -> view abstract
Chretien M;Seidah NG;Basak A;Mbikay M;, (2008 Oct), Proprotein convertases as therapeutic targets, Expert Opinion on Therapeutic Targets, Vol.12, Issue 10, 1289-1300 -> view abstract
Dewpura T;Raymond A;Hamelin J;Seidah NG;Mbikay M;Chretien M;Mayne J;, (2008 Jul), PCSK9 is phosphorylated by a Golgi casein kinase-like kinase ex vivo and circulates as a phosphoprotein in humans, FEBS Journal, Vol.275, Issue 13, 3480-3493 -> view abstract
Basak A;Shervani NJ;Mbikay M;Kolajova M;, (2008 Aug), Recombinant proprotein convertase 4 (PC4) from Leishmania tarentolae expression system: purification, biochemical study and inhibitor design, Protein Expression & Purification, Vol.60, Issue 2, 117-126 -> view abstract
Mayne J;Dewpura T;Raymond A;Cousins M;Chaplin A;Lahey KA;Lahaye SA;Mbikay M;Ooi TC;Chretien M;, (2008), Plasma PCSK9 levels are significantly modified by statins and fibrates in humans, Lipids in Health & Disease, Vol.7, 22 -> view abstract
Note: This is not a complete list of publications. More publications may be available in The Ottawa Hospital Library database and Pubmed (search by last name and initials).
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