Positions

Associate Professor
Pharmacology and Chemical Biology
Baylor College of Medicine
Houston, TX, US
Faculty Senator
Baylor College of Medicine
Houston, Texas, United States
Member
Dan L Duncan Comprehensive Cancer Center
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 discovery and development of novel small molecule inhibitors of biologically important proteins, targeting cancer and infectious diseases. These compounds will be used 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. Novel chemical probes targeting epigenetic (histone/DNA modification) proteins: We have recently discovered novel inhibitors of histone H3-lysine79 (H3K79) methyltransferase DOT1L, H3K4 demethylase LSD1, and histone acetyltransferase p300/CBP. These compounds were found to have selective activity against MLL-rearranged leukemia and other cancers. We are actively exploring functions of several other epigenetic proteins in cancer, designing and synthesizing potent and selective inhibitors as potential therapeutics.

2. Drug discovery targeting Zika and Dengue viruses, which are important human pathogens. Through compound screening followed by medicinal chemistry, a novel series of compounds were identified, for the first time, to be potent and drug-like inhibitors of Zika and Dengue virus proteases. These compounds exhibited potent in vitro and in vivo antiviral activity. Optimization of activity as well as drug properties is on-going, in an effort to find drug candidates to prevent and treat Zika and Dengue infections.

3. Chemical probes targeting cancer-associated gene mutations: Genetic studies show that a high frequency of IDH (isocitrate dehydrogenase) mutation was identified in glioma (75%), AML (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.

Selected Publications

Projects

Chemical probes targeting cancer-associated gene mutations
Drug discovery and mechanistic studies targeting epigenetic proteins
Drug Discovery Targeting Zika and Dengue Viruses

Funding

Chemical Probes Targeting Gliomas with IDH Mutation
- #R01NS080963 (PI)
Grant funding from NIH/NINDS
Drug Discovery and Mechanistic Studies of Protein Methylation Targeting Leukemia
- #RP150129 (PI)
Grant funding from CPRIT
Antiviral Drug Discovery Targeting Zika Virus Protease
- #W81XWH-18-1-0368 (PI)
Grant funding from DOD/CDMRP
Novel Small Molecule Probes Targeting Histone Acetyltransferase p300/CBP
- #RP180177 (PI)
Grant funding from CPRIT