Current Research:

Our interests are focused on using X-ray crystal structural, molecular and biochemical multidisciplinary approaches to study the protein structure and function with emphasis on their implications on drug discovery and therapeutics. Nuclear receptors work as ligand inducible transcription factors and they are among the most successful drug targets in history. There are 48 nuclear receptors in human including classic steroid hormone receptors for estrogen, progesterone, androgens, and glucocorticoids, as well as receptors for peroxisome proliferator activators, vitamin D, vitamin A, and thyroid hormones. The nuclear receptor peroxisome proliferator activated receptor gamma (PPARgamma) is expressed at highest level in adipose tissue and is a key transcription factor involved in adipocyte differentiation. Thiazolidinedione (TZD) ligands that bind and activate PPARgamma are currently used in the treatment of type 2 diabetes in humans. Moreover, PPARgamma also has been closely associated with cancer. To understand the molecular basis of ligand-mediated signaling of PPARgamma in cancer and diabetes, we are interested in determining X-ray crystal structures PPAR/ligand/cofactor complexes and defining the structure/function relationships. The functional implications of the key structural elements that affect the binding of ligand and coactivator are assessed using in vitro AlphaScreen assays and in vivo cell-based assays. This study will provide important insights into biological implications of the PPARgamma and their ligands on cancer and diabetes, and thus lead to structure-based drug design for highly selective and efficient forms for human therapeutics uses.

Bio:

Dr. Yong Li is an Assistant Professor of Department of Pharmaceutical Sciences and Center for Pharmacogenetics, University of Pittsburgh. He also holds a joint faculty position at the Departments of Structural Biology. Before he joined the University of Pittsburgh, he was a Research Scientist at Van Andel Research Institute locate at Grand Rapids, Michigan. Dr. Li received his Biology B.S. degree in 1990 from Nanjing University in China, and his Ph.D. in Molecular Biology from University of South Florida in 1993, followed by a Post-doctoral training at University of Pennsylvania School of Medicine. He also received a Post-doctoral training on Computational Biology at Fox Chase Cancer Center in Philadelphia, Pennsylvania. He became a faculty at the University of Pittsburgh School of Pharmacy in 2007. The research focus of Dr. Li's laboratory is structural and functional studies of nuclear receptor signaling. Research in Dr. Li’s lab has been supported by NIH and American Heart Association (AHA).