Our lab is interested in exploring the molecular regulation of lipid synthesis and pursuing approaches to treat obesity and obesity-related diseases.  Lipogenesis encompasses the process of fatty acid and triglyceride synthesis.  There are several enzymes involved in lipogenesis including acetyl-CoA carboxylase (ACC1/ACC2), fatty acid synthase (FAS), and stearoyl-CoA desaturase 1 (SCD1).  Our study focuses on the molecular mechanism of regulating lipogenesis in response to environmental signals, and we will use metabolomic approaches to define intermediates and metabolic pathways that are relevant to lipogenesis, which will enable to determine the key enzymes for targeting.

             To investigate the molecular basis of lipogenesis, we have shown that ACC1/ACC2 is phosphorylated and inhibited through AMP-activated protein kinase (AMPK) in response to glucagon.  The metabolic sensor AMPK is stimulated upon fasting, exercise and calorie restriction to augment lipid and glucose metabolism.  Myc is a well-known oncogenic protein in controlling cell growth and proliferation.  Highly expressed oncogenic Myc has been shown to favor the conversion of glucose to lactate and increase the uptake and usage of glutamine in cancer cells.  Both AMPK and Myc are key molecules regulating metabolic adaptations in response to environmental nutrients and hormones.  Epigenetic regulation by means of DNA methylation has an important role in controlling gene expression but do not involve mutations of the DNA itself.  We have recently shown that Myc functions as epigenetic regulators to mediate gene expression.  Therefore, we are interested in investigating mechanotransduction (i.e., AMPK and Myc signaling), transcriptional and epigenetic regulation of lipogenesis in adipocytes, hepatocytes and cancer cells.  We also want to determine the key enzymes for targeting in cancer metabolism and translation to the clinic.