Positions

Associate Professor
Pharmacology and Chemical Biology
Baylor College of Medicine
Houston, TX, US
Faculty Senator
Baylor College of Medicine
Houston, Texas, United States

Education

Post-Doctoral Fellowship at University Of Illinois, Urbana-Champaign
Post-Doctoral Fellowship at Tokyo Institute Of Technology
PhD from National University Of Singapore

Professional Interests

  • Drug Discovery, Medicinal Chemistry and Chemical Biology

Professional Statement

We are interested in rational design and development of novel small molecule inhibitors of biologically important proteins targeting cancer and infectious diseases. These compounds will be exploited as chemical probes to find new cancer biology (Chemical Biology), or further developed to become clinically useful drugs (Drug Discovery). These goals will be achieved by using a combination of rational, computational drug design, synthetic chemistry, protein x-ray crystallography, high-throughput screening, biological activity testing, and molecular & cell biology.

Our currently active projects include

1. Chemical probes targeting cancer-associated gene mutations: Genetic studies show that a high frequency of IDH (isocitrate dehydrogenase) mutation was identified in glioma (75%), acute myeloid leukemia (20%) and other types of cancer. Biochemical studies as well as clinical evidence suggest IDH mutation plays important roles in cancer initiation and/or progression. We are using a combination of chemical, biophysical and molecule & cell biology methods to develop novel chemical probes targeting IDH mutation and investigate cancer biology of mutant IDH.

2. Drug discovery targeting histone modifying enzymes: We have recently discovered novel inhibitors of histone H3-lysine79 (H3K79) methyltransferase DOT1L. These compounds were found to have selective activity against MLL-rearranged leukemia. Using these specific inhibitors as probes, we also found DOT1L plays important roles in breast cancer. We are actively exploring functions of several other histone modifying enzymes in cancer, designing and synthesizing potent and selective inhibitors as potential therapeutics.

3. Mechanistic studies of protein methylation in cancer (AML and breast cancer).

Selected Publications

Projects

Chemical probes targeting cancer-associated gene mutations
Genetic studies show that a high frequency of IDH (isocitrate dehydrogenase) mutation was identified in glioma (75%), acute myeloid leukemia (20%) and other types of cancer. Biochemical studies as well as clinical evidence suggest IDH mutation plays important roles in cancer initiation and/or progression. We are using a combination of chemical, biophysical and molecule & cell biology methods to develop novel chemical probes targeting IDH mutation and investigate cancer biology of mutant IDH.
Drug discovery and mechanistic studies targeting histone modifying enzymes
We have recently discovered novel inhibitors of histone H3-lysine79 (H3K79) methyltransferase DOT1L. These compounds were found to have selective activity against MLL-rearranged leukemia. Using these specific inhibitors as probes, we also found DOT1L plays important roles in breast cancer. We are actively exploring biological functions of several other histone modifying enzymes (e.g., LSD1, PRMTs) in cancer, designing and synthesizing potent and selective inhibitors as potential therapeutics.

Funding

Chemical Probes Targeting Gliomas with IDH Mutation
- #R01NS080963 (PI)
Grant funding from NIH/NINDS
Novel Inhibitors of Cancer-Associated Mutations
- #RP140469 (PI)
Grant funding from CPRIT
Drug Discovery and Mechanistic Studies of Protein Methylation Targeting Leukemia
- #RP150129 (PI)
Grant funding from CPRIT