I am interested in drug discovery and development for diabetes and obesity. My research employs multi-discipline tools and NMR/MRI techniques to facilitate the development of new classes of drugs for diabetes. I also investigate the corresponding fundamental mechanisms of metabolism and regulation of signaling networks. One ongoing study focuses on a drug lead, PS10, targeting pyruvate dehydrogenase kinases (PDKs). PDKs negatively regulate the activity of mitochondrial pyruvate dehydrogenase complex (PDHC). PDHC oxidizes pyruvate to acetyl CoA that feeds into TCA cycle for energy production and anaplerosis. The strategic role of PDHC controlling the glucose oxidation in cells makes it a great drug target. Applications of PDK inhibitor that can activate PDHC are various, including diabetes, cancer, heart failure etc. We are taking advantage of the advanced NMR/MRI coupled with hyperpolarized 13C tracers to study the metabolic networks altered by small molecules, as well as to develop methods for future clinical assessment of drug intervention.
- Drug discovery and development
- Hyperpolarized 13C tracer NMR/MRI
- Type 2 diabetes and Obesity
- A Novel Inhibitor of Pyruvate Dehydrogenase Kinase Stimulates Myocardial Carbohydrate Oxidation in Diet-Induced Obesity.
- Wu CY, Satapati S, Gui W, Wynn RM, Sharma G, Lou M, Qi X, Burgess SC, Malloy C, Khemtong C, Sherry AD, Chuang D, Merritt ME J. Biol. Chem. 2018 May
- Targeting hepatic pyruvate dehydrogenase kinases restores insulin signaling and mitigates ChREBP-mediated lipogenesis in diet-induced obese mice.
- Wu CY, Tso SC, Chuang JL, Gui WJ, Lou M, Sharma G, Khemtong C, Qi X, Wynn RM, Chuang DT Mol Metab 2018 Mar
- Studies toward the Unique Pederin Family Member Psymberin: Structure-Activity Relationships, Biochemical Studies and Genetics Identify the Mode-of-Action of Psymberin.
- Wu CY, Feng Y, Cardenas ER, Williams NS, Floreancig PE, De Brabander JK, Roth MG J. Am. Chem. Soc. 2012 Oct
- Development of Dihydroxyphenyl Sulfonylisoindoline Derivatives as Liver-Targeting Pyruvate Dehydrogenase Kinase Inhibitors.
- Tso SC, Lou M, Wu CY, Gui WJ, Chuang JL, Morlock LK, Williams NS, Wynn RM, Qi X, Chuang DT J. Med. Chem. 2017 Jan
- Photophysical studies of anion-induced colorimetric response and amplified fluorescence quenching in dipyrrolylquinoxaline-containing conjugated polymers.
- Wu CY, Chen MS, Lin CA, Lin SC, Sun SS Chemistry 2006 Mar 12 8 2263-9