Chandanamali Punchihewa, PhD
Postdoctoral Fellow
St. Jude Childrens Research Hospital
Memphis, TN
PhD (2006)
Advisor: Dr. Danzou Yang
While at the University of Arizona, my research focused on DNA and DNA interacting proteins as anticancer drug targets. DNA is both the oldest and newest of targets for cancer therapy. A renewed interest in targeting DNA lies in the development of sequence-specific DNA binders. My studies on DNA interacting agents were initiated with the DNA intercalator campotothecin, and also included its target, topoisomerase I enzyme. I have evaluated the structure of topoisomerase I C-terminal domain that consists of the active site tyrosine. With regard to camptothecins, I have evaluated the DNA interactions of the camptothecin analogue homocamptothecin, and also the mechanism of topoisomerase I mediated inhibition of HIF-1 by camptothecin.
In addition, I have also been involved with the determination of the mechanism of actionof another DNA binder, XR5944. Although shown to be a potent inhibitor of cell proliferation, its mechanism of action was not clearly identified. Our biochemical data, and the NMR structural data obtained in the lab, collectively show XR5944 to be an inhibitor of the DNA binding and the subsequent transcriptional activity of specific transcription factors. Focusing on DNA as a drug target, I have also studied specific secondary structures of DNA, the G-quadruplexes. Specifically I have analyzed the folding conformations of G-quadruplexes formed by human telomeric sequences.
I am currently working at the St Jude Children’s Research Hospital as a postdoctoral fellow. My research is focused on identification of inhibitors of protein-protein interaction in treatment of cancer. We target specific proteins in signaling pathways that are more active in cancer cells compared to normal cells. The interactions between different protein partners are investigated in order to rationally design inhibitors of such interactions. Subsequently, different chemical libraries are designed, synthesized and evaluated for their ability to specifically inhibit relevant protein interactions leading to cell apoptosis.