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Awards

• Anna Lee Memorial Lecturer, Harvard Medical School
• ß÷ßäÉçÇø 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

H. Wang, C. Nikain, J. Amengual, M. La Forest, Y. Yu, M.C. Wang, R. Watts, R. Lehner, Y. Qiu, M. Cai, I.J. Kurland, I.J. Goldberg, S. Rajan, M.M. Hussain, J.L. Brodsky, E.A. Fisher. (2024) FITM2 deficiency results in ER lipid accumulation, ER stress, reduced apolipoprotein B lipidation, and VLDL triglyceride secretion in vitro and in mouse liver. Mol Metab 90, 102048.  DOI:

R. Selvaraj, S. Zehnder, R. Watts, J. Lian, C. Das, R. Nelson, R. Lehner. (2023) Preferential lipolysis of DGAT1 over DGAT2 generated triacylglycerol in Huh7 hepatocytes Biochim Biophys Acta – Mol Cell Biol Lipids 1868 (10) :159376. DOI: 

R. Datta, M. Gholampour, C. Yang, R. Volk, S. Lin, M. Podolsky, T. Arnold, F. Rieder, B. Zaro, M. Verzi, R. Lehner, N. Abumrad, C. Lizama, K. Atabai. (2023) MFGE8 links absorption of dietary fatty acids with catabolism of enterocyte lipid stores through HNF4gamma- dependent transcription of CES enzymes. Cell Rep 42(3):112249. DOI: 

S-H. Park, W. Seo, M-J Xu, B. Mackowiak, Yuhong Lin, Y. He, Y. Fu, S. Hwang, Y. Guan, D. Feng, L. Yu, R. Lehner, S. Liangpunsakul, B. Gao. (2023) Ethanol and its nonoxidative metabolites promote acute liver injury by inducing ER stress, adipocyte death and lipolysis.  Cell Molecular Gastroenterol Hepatol 15, 281-306. DOI: 

G. Li, X. Li, I. Mahmud, J. Ysaguirre, B. Fekry, S. Wang, B. Wei, K. Eckel-Mahan, P. Lorenzi, R. Lehner, K. Sun (2023) Interfering with Lipid Metabolism through Targeting CES1 Sensitizes Hepatocellular Carcinoma for Chemotherapy. JCI Insight 8(2):e163624. DOI: 

A. Hussain, J. Lian, R. Watts, T. Gutierrez, R. Nelson, I-S. Goping, R. Lehner. (2022) Attenuation of Obesity induced hyperlipidemia reduces tumor growth. Biochim Biophys Acta - Mol Cell Biol Lipids 1867 (4): 159124. DOI:

I. Anastasia, N. Ilacqua, A. Raimondi, P. Lemieux, R. Ghandehari-Alavijeh, G. Faure, S.L. Mekhedov, K.J. Williams, F. Caicci, G. Valle, M. Giacomello, A.D. Quiroga, R. Lehner, M.J. Miksis, K. Toth, T.Q. de Aguiar Vallim, E.V. Koonin, L. Scorrano, L. Pellegrini. (2021) Mitochondria-rough-ER contacts in the liver regulate systemic lipid homeostasis. Cell Rep 34(11):108873. DOI: 

J. Lian, J.N. van der Veen, R. Watts R, R.L. Jacobs, R. Lehner. (2021) Carboxylesterase 1d (Ces1d) does not contribute to cholesteryl ester hydrolysis in the liver. J Lipid Res 62:100093. DOI: 

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: 

A.D. Quiroga, R. Lehner. (2018) Pharmacological intervention of liver triacylglycerol lipolysis: The good, the bad and the ugly. Biochem Pharmacol 155, 233-241. DOI: 

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: 

J. Lian, W. Bahitham, R. Panigrahi, R. Nelson, L. Li, R. Watts, A. Thiesen, M.J. Lemieux and R. Lehner. (2018) Genetic variation in human carboxylesterase CES1 confers resistance to hepatic steatosis. Biochim Biophys Acta – Mol Cell Biol Lipids 1863, 688-699. DOI: 

J. Lian, R. Nelson and R. Lehner. (2018) Carboxylesterases in lipid metabolism: from mouse to human. Protein Cell 9, 178-195. DOI: 

C.C. Lord, D. Ferguson, G. Thomas, A.L. Brown, R.C. Schugar, A. Burrows, A.D. Gromovsky, J. Betters, C. Neumann, J. Sacks, S. Marshall, R. Watts, M. Schweiger, R.G. Lee, R.M. Crooke, M.J. Graham, J.D. Lathia, T.F. Sakaguchi, R. Lehner, G. Haemmerle, R. Zechner and J.M. Brown. (2016) Regulation of hepatic triacylglycerol metabolism by CGI-58 does not require ATGL co-activation. Cell Rep 16, 939-949. DOI: 

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

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: 

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. DOI: 

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

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 – Mol Cell Biol Lipids 1831, 1113-1123. DOI: 

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. DOI: 

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. DOI: 

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. DOI: 

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. DOI: 

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. DOI: 

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.  DOI: 

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Laboratory Members

Research Associate
Jihong Lian

Technicians
Russell Watts

Graduate Student
Giacomo Perri (co-supervisor)

Research Assistant
Phung Tu