Kiran Mahajan Lab

RESEARCH PROGRAM

Targeting Epigenetic Regulators of Lethal Prostate Cancers

Our overarching goal is to characterize epigenetic regulators promoting survival, adaptability and metastasis of lethal cancers, particularly hormone refractory prostate cancers and characterize  novel small molecule inhibitors that we have identified as having potent anti-tumor activity against metastatic prostate cancers.  Our laboratory is focused on characterizing the mechanism of action of lineage-specific transcription factors, particularly HOXB13, tyrosine kinases and novel non-coding RNAs as epigenetic regulators of disease specific targets. By identifying novel therapeutic vulnerabilities we have uncovered epigenomic mechanisms driving plasticity of castration-resistant prostate cancers. The overall idea is to develop a robust pharmacogenomics pipeline to advance novel inhibitors as cancer therapeutics.

A second interest of our lab which is integral to the existing interest in prostate cancer, is the epigenetic regulation of DNA damage signaling pathways. Based on the notion that genome instability drives tumor heterogeneity, clonal adaptation and drug resistance, and intact DNA repair pathways are critical to maintain the integrity of the genomes, we are characterizing novel regulators of genome stability and how these may be compromised as prostate cancer progresses to castration resistant stage.