Lehner, Richard - University of Alberta

研究领域

Triacylglycerol and cholesterol metabolism (cell biology of obesity, cardiovascular disease, fatty liver disease and production of hepatitis C virus) Excessive triacylglycerol (TG) storage is manifested as obesity, a recognized health risk factor for Type 2 diabetes, non-alcoholic fatty liver disease, cardiovascular disease and some cancers. TG is secreted by the liver into circulation in very-low density lipoprotein (VLDL) particles. VLDL is converted in blood to low-density lipoprotein (LDL) - a carrier of "bad" cholesterol. In our laboratory we are investigating the role of endoplasmic reticulum localized lipid hydrolases in TG and cholesterol metabolism and transport and their potential as pharmacological targets for treatment of lipid metabolic disorders and viral infection. I. Carboxylesterase 1d/Triacylglycerol hydrolase (Ces1d/TGH): Hypothesis: TGH is involved in the mobilization of intracellular TG stores in the liver. Project involves cell biology (role of TGH in lipid droplet formation and turnover) and physiology (analysis of TGH transgenic and knock out mice and human TGH mutations). II. Carboxylesterase 1g/Esterase-x (Ces1g/Es-x): Hypothesis: Es-x regulates in lipid storage and secretion. Project involves studies on the role of the enzyme in lipid metabolism in the intestine as well as in the liver utilizing cell biology and molecular biology approaches and analysis of Es-x knockout mice. III. Arylacetamide deacetylase (AADAC): Hypothesis: AADAC participates in intestinal and hepatic lipid metabolism. Project involves cell biology of retention of AADAC in the endoplasmic reticulum; studies on the role of the enzyme in lipid metabolism in hepatocytes and in AADAC transgenic and knock out mice. Role of AADAC in the regulation of sterol metabolism and HCV infection.

近期论文

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C. Li, L. Li, J. Lian, R. Watts, R. Nelson, B. Goodwin and R. Lehner. (2015) Roles of acyl-CoA: diacylglycerol acyltransferases 1 and 2 in triacylglycerol synthesis and secretion in primary hepatocytes. Arteriocler. Thromb. Vasc. Biol. (in press) C.A. Goard, M. Chan-Seng-Yue, P.J. Mullen, A.D. Quiroga, A.R. Wasylishen, J.W. Clendening, D.H. Sendorek, S. Haider, R. Lehner, P.C. Boutros, and L.Z. Penn. (2014) Identifying molecular features that distinguish fluvastatin-sensitive breast tumor cells. Breast Cancer Res Treat. 143, 301-312 H. Wang, A.D. Quiroga and R. Lehner. (2013) Analysis of lipid droplets in hepatocytes. Methods in Cell Biology 16, 107-127 B. Erickson, S. P. Selvan, K.W.S. Ko, K. Kelly, A.D. Quiroga, L. Li, R. Nelson, K. King-Jones, R.L. Jacobs and R. Lehner. (2013) Endoplasmic reticulum-localized hepatic lipase decreases triacylglycerol storage and VLDL secretion. Biochim. Biophys. Acta-MCBL 1831, 1113-1123 M. Nourbakhsh, D.N. Douglas, J.T. Lewis, C.H. Pu, T.M. Kawahara, R. Nelson, A.D. Quiroga, R. Lehner, and N.M. Kneteman. (2013) Arylacetemide deacetylase: A triacylglycerol lipase that is ablated in hepatoma cells during infectious Hepatitis C viral production. J. Hepatol. 59, 336-343 A.D. Quiroga, J. Lian and R. Lehner (2012) Carboxylesterase1/esterase-x regulates chylomicron production in mice. PLoS One 7, e49515 J. Lian, A.D. Quiroga, L. Li and R. Lehner. (2012) Ces3/TGH deficiency improves dyslipidemia and reduces atherosclerosis in Ldlr-/- mice. Circ. Res. 111, 982-990 A.D. Quiroga, L. Li, M. Trötzmüller, R. Nelson, S.D. Proctor, H. Köfeler, and R. Lehner. (2012) Deficiency of Carboxylesterase1/Esterase-x in mice results in obesity, hepatic steatosis and hyperlipidemia. Hepatology 56, 2188-2198 J. Lian, E. Wei, S. Wang, A.D. Quiroga, L. Li, A. Di Pardo, J. van der Veen, S. Sipione, G.A. Mitchell and R. Lehner. (2012) Liver specific inactivation of Ces3/TGH decreases blood lipids without causing severe steatosis. Hepatology 56, 2154-2162 Q. Liu, R.M.P. Solito, R. Lehner, S.J. Stone and R.J. Weselake. (2012) Acyl-CoA:diacylglycerol acyltransferase: molecular biology, biochemistry and biotechnology. Prog. Lipid Res. 51, 350-377 R. Lehner, J. Lian and A.D. Quiroga. (2012) Lumenal lipid metabolism: Implications for lipoprotein assembly. Arterioscler. Thromb. Vasc. Biol. 32, 1087-1093 A.D. Quiroga and R. Lehner. (2011) Role of endoplasmic reticulum neutral lipid hydrolases. Trends Endocrinol. Metab. 22, 21-225 R. Holmes, M. Wright, S. Laulederkind, L. Cox, M. Hosokawa, T. Imai, S. Ishibashi, R. Lehner, M. Miyazaki, P. Potter, M. Redinbo, J. Robert, T. Satoh, T. Yamashita, B. Yan, T. Yokoi, R. Zechner and L. Maltais. (2010) Recommended nomenclature for five mammalian carboxylesterase gene families: Human, mouse and rat genes and proteins. Mamm. Genome 21, 427-441 H. Wang, E. Wei, A.D. Quiroga, X. Sun, N. Touret and R. Lehner (2010) Altered lipid droplet dynamics in hepatocytes lacking triacylglycerol hydrolase expression. Mol. Biol. Cell 21, 1991-2000 Li, P. Boutros, A. Martirosyan, R. Lehner, I. Jurisica, S. Trudel and L. Penn (2010) Exploiting the mevalonate pathway to distinguish statin-sensitive multiple myeloma. Blood 115, 4787-4797 E. Wei, Y. Ben Ali, J. Lyon, H. Wang, Randy Nelson, V.W. Dolinsky, J. R. Dyck, G. A. Mitchell, G. S. Korbutt and R. Lehner (2010) Loss of TGH/Ces3 in mice decreases blood lipids, improves glucose tolerance and increases energy expenditure. Cell Metab. 11, 183-193 H. Wang, D. Gilham and R. Lehner (2007) Proteomic and lipid characterization of apolipoproteinB-free luminal lipid droplets from mouse liver microsomes: Implications for very-low density lipoprotein assembly. J. Biol. Chem. 282, 33218-33226 E. Wei, W. Gao and R. Lehner (2007) Attenuation of adipocyte triacylglycerol hydrolase activity decreases basal fatty acid efflux. J. Biol. Chem. 282, 8027-8035 D. Gilham and R. Lehner (2005) Techniques to measure lipase and esterase activity in vitro. Methods 36, 139-147 D. Gilham, M. Alam, W. Gao, D.E. Vance and R. Lehner (2005) Triacylglycerol hydrolase is localized to the ER by an unusual retention sequence where it associates with nascent VLDL without utilizing the component lipids as substrates. Mol. Biol. Cell 16, 984-996