Research Overview

A major interest in our lab is to determine how tyrosine phosphorylation regulates processes that affect cancer cell survival and tumor progression. We have used Ack1 (also known as ACK, TNK2, or activated Cdc42 kinase) tyrosine kinase to tease out some of the major survival pathways active in cancer and normal cells.

Some of major findings of our lab include:

• We demonstrated that Ack1 integrates signal from multiple receptor tyrosine kinases, which opened the doors for research into this kinase as a potential drug target. Amgen and later our lab synthesized a small molecule inhibitor, AIM-100, which inhibits Ack1 signaling and suppresses cancer cell growth.

• We first reported androgen receptor (AR) to be Ack1 substrate and identified two novel phosphorylation sites in AR, Tyrsoine 267 and 363. The tyrosine phosphorylation of AR was shown to be the major mechanisms for progression of prostate cancer to hormone-refractory stage (also called as AICaP, AIPC or CRPC).

• We also identified a novel phosphorylation site, Tyrosine 176, in AKT. AKT tyrosine 176 phosphorylation correlated with breast cancer progression to metastatic stages and inversely correlated with patient survival

 



Mahajan K et al. J. Cell. Physiol. 224: 327-333, 2010.

Current Projects
• Characterization of Ack1 knockout mice to assess physiological role of Ack1/AKT signaling
• Role of Ack1/AR signaling in radioresistant prostate cancer

Postdoctoral Opportunities


We are currently interested in hiring two postdoctoral fellows and research associates in our lab, If interested, please send your CV and names of three references at


Nupam.mahajan@moffitt.org

 

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