Research Interests:
The specific goal of our laboratory is to unravel the mechanisms of action of Ack1 tyrosine kinases in prostate and breast cancer. We serendipitously discovered that activated Ack1 tyrosine phosphorylated Androgen Receptor (AR), which resulted in transcriptional activation of AR responsive genes, PSA and hK2. Interestingly, the activated Ack1 expressing LNCaP cells formed tumors in castrated nude mice, suggesting that activated Ack1 could confer hormone refractory tumor growth by permitting tyrosine phosphorylated AR to function at significantly lower levels of androgen. Further, it was observed that heregulin mediated HER2 activation could lead to Ack1 activation which in turn activated AR transcription activation. Most significantly, we demonstrated for the first time that AR is tyrosine phosphorylated (Tyr 267 and Tyr363) in primary Androgen-independent tumors (in about 45% patients) and phosphorylation is highly correlated to Ack1 activation in those patients. (Mahajan et al., PNAS, 2007). Currently we are focusing on studying potential role of activated Ack1 in hormone-refractory prostate cancer using a mouse model. Further, we are interested in identification of Ack1-interacting molecules that are involved in progression of hormonally regulated cancers. The second area of interest is to develop novel anticancer drugs based on targeting Ack1 tyrosine kinase. This study could pave the way for development of novel therapeutic strategies in advanced prostate and breast cancer.