Richard Lehner

Awards

• Anna Lee Memorial Lecturer, Harvard Medical School
• Alberta Innovates - Health Solutions Scientist
• Pfizer Cardiovascular Research Award
• Simon-Pierre Noel Lectureship

Research Interests

Triacylglycerol and cholesterol metabolism (cell biology of obesity, cardiovascular disease, fatty liver disease and cancer)

Excessive fat (triacylglycerol, TG) storage in lipid droplets (LDs) 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, viral infection and cancer.

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. Role of DGAT1 and DGAT2 in lipid droplet (LD) dynamics:

Hypothesis: LDs containing TG synthesized by DGAT1 have a distinct set of proteins and possibly lipid composition from those synthesized by DGAT2. Project involves studies on the role of TG synthesizing enzymes (DGAT1 and DGAT2) in lipid storage metabolism in hepatocytes and other cell types utilizing cell biology, biochemistry and molecular biology approaches.

III. Arylacetamide deacetylase (AADAC):

Hypothesis: AADAC regulates hepatic lipid storage and 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 (Tg) and knock out (KO) mice.

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Selected Publications

Anastasia I, Ilacqua N, Raimondi A, Lemieux P, Ghandehari-Alavijeh R, Faure G, Mekhedov SL, Williams KJ, Caicci F, Valle G, Giacomello M, Quiroga AD, Lehner R, Miksis MJ, Toth K, de Aguiar Vallim TQ, Koonin EV, Scorrano L, Pellegrini L. (2021) Mitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasis. Cell Rep. 34(11):108873. doi: 10.1016/j.celrep.2021.108873.

Lian J, van der Veen JN, Watts R, Jacobs RL, Lehner R. (2021) Carboxylesterase 1d (Ces1d) does not contribute to cholesteryl ester hydrolysis in the liver. .J Lipid Res. 62:100093. doi: 10.1016/j.jlr.2021.100093. Epub 2021 Jun 18.

J. Lian, R. Watts, A.D. Quiroga, M.R. Beggs, R.T. Alexander, R. Lehner. (2019) Ces1d deficiency protects against high-sucrose diet-induced hepatic triacylglycerol accumulation. J. Lipid Res. 60, 880-891. doi: 10.1194/jlr.M092544

D.A. Kramer, A.D. Quiroga, J. Lian, R.P. Fahlman, R. Lehner. (2018) Fasting and refeeding induces changes in the mouse hepatic lipid droplet proteome. J Proteomics 181, 213-224. doi: 10.1016/j.jprot.2018.04.024.

J. Lian, R. Nelson, R. Lehner. (2017) Carboxylesterases in lipid metabolism: from mouse to human. Protein Cell doi: I 10.1007/s13238-017-0437-z

J. Lian, E. Wei, J. Groenendyk, S.K. Das, M. Hermansson, L.Li, R. Watts, A. Thiesen, G.Y. Oudit, M. Michalak, R. Lehner. (2016) Ces3/TGH deficiency attenuates steatohepatitis. Sci. Rep. 6, 25747. doi: 10.1038/srep25747

J. Huang, L. Li, J. Lian, S. Schauer, P.W. Vesely, D. Kratky, G. Hoefler and R. Lehner. (2016) Tumor-induced hyperlipidemia contributes to tumor growth. Cell Rep. 15, 336-348. doi: 10.1016/j.celrep.2016.03.020

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.35, 1080-1091

H. Wang, A.D. Quiroga and R. Lehner. (2013) Analysis of lipid droplets in hepatocytes. Methods in Cell Biol. 116, 107-127

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

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

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

E. Wei, Y. Ben Ali, J. Lyon, H. Wang, R. 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

 

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Laboratory Members

Research Associate
Jihong Lian

Technicians
Randy Nelson
Russell Watts

Postdoctoral Fellow
Dr. Chinmayee Das

Graduate Student
Maximilian Schinagl

Research Assistant
Phung Tu