Projects

Genetic studies show that a high frequency of IDH (isocitrate dehydrogenase) mutation was identified in glioma (75 percent), AML (20 percent) 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.

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.

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.

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