Home

Publications

 Group

Research

Classes

Research Interests:
The research in my laboratory has three major directions:

1. Elucidate kinetic mechanisms of enzymes involved in DNA/RNA replication, repair, and lesion bypass
2. Understand Hepatitis C (HCV) replication and regulation of innate immunity
3. Develop antiviral and anti-cancer molecules based on rational drug design.

In kinetic studies, we use a variety of pre-steady state kinetic methods including rapid chemical quench-flow and stopped-flow. These methods allow us to quench reactions in milliseconds, and extract more kinetic information than the traditional steady-state kinetic methods. We also use protein engineering methods including site-directed mutagenesis and domain-swapping to study structure-function relationship in these enzymes. Moreover, we are using the femtosecond-resolved fluorescence up-conversion techniques to study the enzyme-substrate interactions in the collaboration with the group of Dr. Dongping Zhong at Dept. of Physics, OSU. These studies will allow us to develop new methods and also push enzymology to an unprecedented territory. Our goals are to understand the elementary steps of reactions occurred at the active sites of enzymes. Then, these mechanisms will aid our rational drug design. The designed enzyme inhibitors will be synthesized and tested in vitro and in vivo. We are currently investigating several systems described below.

(1) Pre-Steady State Kinetic Studies of DNA Lesion Bypass Polymerases

(2) Kinetic and Protein-Protein Interaction Studies of Human DNA Polymerases l, µ and TdT

(3) Mechanistic Studies of Vaccinia Virus DNA Polymerases and Design/Synthesis of Novel Nucleoside Analog Inhibitors

(4) Design and Synthesis of Novel Nucleoside Analog Inhibitors

(5) Developing Anti-HCV Peptide-Based Inhibitors

(6) Effects of HCV Protease NS3/4A on Human Kinases Involved in Immune Response