Pharmaceutica Analytica Acta

Role of epigenetics in the HIF pathway and novel therapeutic opportunities

3^rd International Conference and Exhibition on Pharmaceutics & Novel Drug Delivery Systems

April 08-10, 2013 Hilton Chicago/Northbrook, USA

Mridul Mukherji

Scientific Tracks Abstracts: Pharmaceut Anal Acta

Abstract:

Hypoxia plays critical roles in the pathobiology of heart disease, cancer, stroke, eye, and chronic lung disease, which are responsible for 60% of deaths in the United States. Hypoxia-mediated activation of the hypoxia-inducible-factor (HIF) pathway, leading to transcriptional changes in gene expressions, plays a fundamental role in the pathobiology of above diseases. Yet, molecular and biochemical mechanisms governing this fundamental pathway remain poorly understood. Since our initial identification of first iron(II), 2-oxoglutarate (2OG)-dependent dioxygenase involved in transcription regulation by the HIF pathway (Science, 2001, 292, 468-472; Cell, 2001, 107, 43-54), results from numerous studies have established a key role for these enzymes in epigenetic transcriptional regulation. Our long term goal is to use our experience in the HIF pathway and dioxygenases/demethylases to delineate their roles in normal development/disease states, and identify small molecule modulators that can be used to develop more effective strategies for therapeutic intervention. We have recently shown that hypoxia induces the expression of a number of histone lysine demethylases/dioxygenases (KDMs) in cancer and retinal pigment epithelial cells. Moreover, we found that the expression of pro-angiogenic genes (ADM and GDF15) is dependent on KDMs under hypoxic conditions. Further, treating the cells with a general KDM inhibitor blocks the expression of these pro-angiogenic genes. Results from our studies suggest that specific inhibitors of KDMs such as JMJD1A can be a new therapeutic approach to treat diseases caused by the hypoxia.

Biography :

Mridul Mukherji has completed his Ph.D. at the age of 29 years from the University of Oxford and postdoctoral studies from the Scripps Research Institute. At present, he holds a rank of Assistant Professor at the School of Pharmacy, University of Missouri-Kansas City. He has published more than 26 papers in reputed journals and serving as an editorial board member of Dataset Papers in Biology, Hindawi Publishing Corporation.