H.Lee Moffitt Cancer Center & Research Institute

Research Overview

A major interest in our lab is to determine how tyrosine phosphorylation regulates epigenetic processes that affect cellular homeostasis and cancer cell survival. We employ multiple tyrosine kinases to investigate these processes. The examples are:

WEE1 : A an novel epigenetic modulator & its significance in melanoma

ACK1/TNK2 : Oncogene in prostate, breast, lung and pancreatic cancers

Some of the major findings of our lab include:

  • We demonstrated for the first time that WEE1 kinase is an epigenetic modifier; it phosphorylated histone H2B at Tyrosine 37, regulating global histone output.
  • Recently, we have identified a novel WEE1 epignetic inhibitor.
  • We demonstrated that ACK1 (also known as TNK2) kinase plays crucial role in drug-resistance of prostate, breast & lung cancers.
  • We identified a novel AKT phosphorylation site, Tyrosine 176 that correlated with prostate, breast and pancreatic cancer progression to metastatic stages.
  • Androgen receptor (AR) was shown to be phosphorylated by ACK1 at Tyrosine 267 and 363 in castration resistant prostate cancer or CRPC.
  • ACK1 phosphorylates histone demethylase KDM3A (JHDM2A) at a novel site, Tyr 1114 to regulate the mammary tumor oncogene HOXA1, facilitating tamoxifen-resistance of the breast cancer.
  • We have developed a new class of ACK1 small molecule inhibitor.

     

    Ack1 pathway

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

    Current Projects
    • WEE1 epigenetic signaling
    • ACK1/TNK2 knockout mice
    • Characterization of novel WEE1 and ACK1 small molecule inhibitors
    • Role of ACK1/AR signaling in castration resistant prostate cancer

Dr. Nupam Mahajan

 

Nupam Mahajan, PhD.
Associate Professor
Moffitt Cancer Center

Contact:
SRB-2, Office # 22043
Moffitt Cancer Center
12902 Magnolia Drive
Tampa, Florida 33612

Email:
Nupam.mahajan@moffitt.org

Phone:
Office: 813-745-6684
Lab: 813-745-4078
Fax:: 813-745-6748

Funding Sources:

National Institutes of Health

SPOREs of Lung

National Institute of Health (NIH)/NCI-RO1

Department of Defense (DoD); 2012, 2013 & 2015

Bankhead Coley

Comprehensive Melanoma Research Center

Pardee Foundation

Miles for Moffitt; 2009 & 2015

Celgene