B.S. Nanjing University, China 1984; Ph.D. Purdue University, West Lafayette 1994; Post-Doctoral The Scripps Research Institute, La Jolla 1996
• Protein engineering via total chemical protein synthesis. As chemical engineers of proteins, we are interested in knowing what happens to functional properties of proteins when their side chains and backbone structures are altered in a way that is genetically unattainable. To accomplish this unconventional task, we functionally and structurally characterize proteins that are chemically assembled from (coded and non-coded) individual amino acids. This “chemical protein engineering” approach allows us to address, from a different perspective, important unsolved problems in protein science, thus broadening our knowledge and deepening our understanding of how proteins function at the molecular level.
• Defensins - structure, function and mechanisms of action. Defensins are a family of 2-5 kDa, disulfide-bridged cationic antimicrobial peptides expressed in leukocytes and epithelial cells. They are broadly active against bacteria, fungi, and viruses, playing important roles in innate host defense against microbial infection. Some defensins also neutralize secreted bacterial toxins and can bind host cell receptors to trigger innate inflammatory and adaptive immune responses. Our studies are aimed at deciphering the molecular determinants of diverse functions of human defensins and elucidating their mechanisms of action in a variety of biological processes. Such knowledge may help design new anti-infective peptides to fight off infectious diseases.
• Antiviral and antitumor peptides for targeted molecular therapy. Peptide inhibition of protein-protein interactions is a promising route for the development of novel classes of therapeutic agents for targeted molecular therapy. Compared with small molecule inhibitors, peptides are capable of antagonizing target proteins with high affinity and unsurpassed specificity. This line of research centers on applying the contemporary tools of synthetic protein chemistry, phage display, structural biology, and drug delivery to the discovery of peptide antagonists with desirable pharmacokinetic properties and functionalities that may be explored for therapeutic use. Our targets include but not limited to HIV-1 matrix and capsid proteins as well as oncogenic proteins that negatively regulate the tumor suppressor protein p53.
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