University of South Florida

Cancer Biology Ph.D. Program at the

Nupam Mahajan, Ph.D. Assistant Professor in the Department of Oncologic Sciences Member-in-Residence of the Moffitt Cancer Center, Drug Discovery Program E-mail: Nupam.Mahajan@moffitt.org Phone: (813)745-4078

Training
PhD, Indian Institute of Science, India, 1997
Postdoctoral Fellowship, University of North Carolina, Chapel Hill, NC, 1997-2004
Assistant Professor, University of North Carolina, Chapel Hill, NC, 2004-2007

Research Interests
The specific goal of our laboratory is to unravel the role of tyrosine kinases in initiation of various cancers. We have been using Ack1/TNK2 as a model tyrosine kinase to identify its substrates and novel phosphorylation sites. A tumor suppressor protein Wwox was identified as Ack1 substrate. Ack1 phosphorylated Wwox at Tyr287 that was necessary for degradation of Wwox. Later, we discovered that activated Ack1 tyrosine phosphorylated Androgen Receptor (AR), which resulted in transcriptional activation of AR responsive genes, permitting tyrosine phosphorylated AR to function at significantly lower levels of androgen. We demonstrated for the first time that AR is tyrosine phosphorylated at Tyr267 and Tyr363 in primary Androgen-independent tumors (in about 45% patients). Recently, we have identified few more substrates of Ack1 and their role in prostate and breast tumor progression is being studied. We are also focused on studying role of activated Ack1 in prostate cancer using a mouse model. 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.

Search for publications by:    
This search will be conducted at the US National Library of Medicine (NLM) and PubMed.

Selected Publications

1) Mahajan NP, Liu Y, Majumder S, Warren M, Parker C, Mohler J, Earp H, Whang Y. Activated Cdc42-associated kinase Ack1 promotes prostate cancer progression via androgen receptor tyrosine phosphorylation. Proc Natl Acad Sci U S A. 2007 May;104(20):8438-43

2) Mahajan NP, Whang Y, Mohler J, Earp H. Activated tyrosine kinase Ack1 promotes prostate tumorigenesis: role of Ack1 in polyubiquitination of tumor suppressor Wwox. Cancer Res. 2005 Nov;65(22):10514-10523.

3) Mahajan NP, Earp H. An SH2 domain-dependent, phosphotyrosine-independent interaction between Vav1 and the Mer receptor tyrosine kinase: a mechanism for localizing guanine nucleotide-exchange factor action. J Biol Chem. 2003 Oct;278(43):42596-603.

4) Mahajan NP, Harrison-Shostak D, Michaux J, Herman B. Novel mutant green fluorescent protein protease substrates reveal the activation of specific caspases during apoptosis. Chem Biol. 1999 Jun;6(6):401-409.

5) Mahajan NP, Linder K, Berry G, Gordon G, Heim R, Herman B. Bcl-2 and Bax interactions in mitochondria probed with green fluorescent protein and fluorescence resonance energy transfer. Nature Biotechnology. 1998 Jun;16(6):547-552.