Dominic Ng
PhD
Research Synopsis
Research Interests: My research lab is primarily interested in the area of genetics of lipid disorders, and their roles in diabetes, adiposity and cardiovascular diseases with special emphasis on high density lipoprotein (HDL) metabolism. We use transgenic/knock out mice as models and our tools include in vivo experiments, ex vivo and in vitro assays at tissue, cellular, and molecular levels. We are particularly interested in using in vivo mouse model experiments to examine the impact of various genetic forms of dyslipidemic disorders and their interactions with other dysmetabolic states like insulin resistance, oxidative stress, atherogenesis and thrombogenesis. Detailed analyses of these animal models using cellular, molecular and genetic markers will also be carried out to elucidate the underlying mechanism of such disease processes and their interactions. Such genetic models are also used to study the effects of dietary and novel drug interventions.
I also participate in a number of multi-center randomized control clinical trials in the prevention of cardiovascular diseases and in the treatment of obesity.
Keywords: Animal models, Atherosclerosis, Cell biology, Diabetes, Insulin resistance, lipoproteins, obesity, adipose tissue, lecithin cholesterol acyltransferase, lipids.
PRESENT TRAINEES
Amir Bashiri
PRESENT COLLABORATIONS
Within the Department of Physiology
Tianru Jin
Outside of the Department of Physiology
Khosrow Adeli, Dept of LMP
Philip Connelly, Dept of LMP
Carolyn Cummins, Faculty of Pharmacy
Committee member of national/international scientific organizations Member, National Research Council/Scientific, Canadian Diabetes Association
Member, Board of Directors, Canadian Society of Arteriosclerosis Thrombosis and Vascular Biology
Recent Publications
Ng DS. Diabetic dyslipidemia: from evolving pathophysiological insight to emerging therapeutic targets. Can J Diabetes. 2013 Oct;37(5):319-26.
Nesan D, Ng DS. Recent development in targeting brown adipose tissues for the treatment of cardiometabolic diseases. Curr Opin Lipidol. 2014 Feb;25(1):92-3.
Mancini GB, Tashakkor AY, Baker S, Bergeron J, Fitchett D, Frohlich J, Genest J, Gupta M, Hegele RA, Ng DS, Pearson GJ, Pope J. Diagnosis, prevention, and management of statin adverse effects and intolerance: Canadian Working Group Consensus update. Can J Cardiol. 2013 Dec;29(12):1553-68.
Ng DS. Lecithin cholesterol acyltransferase deficiency protects from diet-induced insulin resistance and obesity--novel insights from mouse models. Vitam Horm. 2013;91:259-70.
Anderson TJ, Grégoire J, Hegele RA, Couture P, Mancini GB, McPherson R, Francis GA, Poirier P, Lau DC, Grover S, Genest J Jr, Carpentier AC, Dufour R, Gupta M, Ward R, Leiter LA, Lonn E, Ng DS, Pearson GJ, Yates GM, Stone JA, Ur E. 2012 Update of the Canadian Cardiovascular Society guidelines for the diagnosis and treatment of dyslipidemia for the prevention of cardiovascular disease in the adult. Can J Cardiol. 2013 Feb;29(2):151-67.
Ng DS, Wong NC, Hegele RA. HDL--is it too big to fail? Nat Rev Endocrinol. 2013;9:308-12.
Hager L, Li L, Pun H, Liu L, Hossain MA, Maguire GF, Naples M, Baker C, Magomedova L, Tam J, Adeli K, Cummins CL, Connelly PW, Ng DS. Lecithin:cholesterol acyltransferase deficiency protects against cholesterol-induced hepatic endoplasmic reticulum stress in mice. J Biol Chem. 2012 Jun 8;287(24):20755-68.
Ng DS. The role of lecithin:cholesterol acyltransferase in the modulation of cardiometabolic risks - a clinical update and emerging insights from animal models.Biochim Biophys Acta. 2012 Apr;1821(4):654-9.
Li L, Tam L, Liu L, Jin T, Ng DS. Wnt-signaling mediates the anti-adipogenic action of lysophosphatidic acid through cross talking with the Rho/Rho associated kinase (ROCK) pathway. Biochem Cell Biol. 2011 Dec;89(6):515-21.
Li L, Hossain MA, Sadat S, Hager L, Liu L, Tam L, Schroer S, Huogen L, Fantus IG, Connelly PW, Woo M, Ng DS. Lecithin cholesterol acyltransferase null mice are protected from diet-induced obesity and insulin resistance in a gender-specific manner through multiple pathways. J Biol Chem. 2011 May 20;286(20):17809-20.
Connelly PW, Picardo CM, Potter PM, Teiber JF, Maguire GF, Ng DS. Mouse serum paraoxonase-1 lactonase activity is specific for medium-chain length fatty acid lactones.Biochim Biophys Acta. 2011 Jan;1811(1):39-45.
Tanigawa H, Billheimer JT, Tohyama J, Fuki IV, Ng DS, Rothblat GH, Rader DJ. Lecithin: cholesterol acyltransferase expression has minimal effects on macrophage reverse cholesterol transport in vivo.Circulation. 2009 Jul 14;120(2):160-9.
Sirek AS, Liu L, Naples M, Adeli K, Ng DS, Jin T. Insulin stimulates the expression of carbohydrate response element binding protein (ChREBP) by attenuating the repressive effect of Pit-1, Oct-1/Oct-2, and Unc-86 homeodomain protein octamer transcription factor-1. Endocrinology. 2009 Aug;150(8):3483-92. Selected Abstracts:
Bashiri A, Tavallaee G, Menard M, Ng DS. “Cholesterol Biosynthesis Upregulation Plays a Crucial Role in Nutritionally Induced Hepatic ER Stress and Inflammation. 82nd European Atherosclerosis Congress (2014), Madrid, Spain (Accepted).
Hager L, Li L, Liu L, Maguire GF, Naples M, Baker C, Magomedova L, Adeli K, Cummins CL, Connelly PW, Ng DS. Lecithin:Cholestrol Acyltransferase Deficiency Protects Against Insulin Resistance Through Prevention of Cholesterol-Induced Hepatic Endoplasmic Reticulum (ER) Stress", European Atherosclerosis Society Annual Scientific Meeting – (2012), Milan Italy.
Hager L, Li L, Liu L, Maguire GF, Naples M, Baker C, Magomedova L, Adeli K, Cummins CL, Connelly PW, Ng DS. Lecithin:cholesterol transferase (LCAT) deficiency mice are resistant to hepatic ER stress and insulin resistance through evasion of cholesterol accumulation in the ER” American Diabetes Association Scientific Meeting (2011), San Diego, California.
Li L, Tam L, Jin T, Ng DS. Cross-talk with Wnt-signaling Mediates Inhibition of Adipogenesis by Lysophosphatidic Acid (LPA). Canadian Lipoprotein Conference 2010. Niagara-on-the-Lake, Ontario, Canada.
Li L, Sadat S, Liu L, Lu H, Hager L, Connelly PW, Fantus IG, Ng DS. LCAT deficient mice developed gender-dependent resistance to diet-induced obesity and insulin resistance in association with altered unfolded protein response. IAS Sponsored HDL Workshop, Whistler, BC 2010