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 specifically in late S phase of cell cycle, regulating global histone output.
  • Recently, we have identified a novel WEE1 epignetic inhibitor that suppressed H2B Tyr37-phosphorylation.
  • We demonstrated that ACK1 (also known as TNK2) kinase plays crucial role in drug-resistance of prostate, breast, ovarian and pancreatic 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 identified to be ACK1 substrate; ACK1 phosphorylates AR at Tyrosine 267 and 363 initiating a distinct trasncriptional program, which was critical for 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, (R)-9b, which not only suppressed ACK1 and its substrate phosphorylations but also compromised tumor growth.


    Ack1 pathway

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

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

    Postdoctoral Opportunities

    We are always interested in dedicated postdoct or research associates in our lab, feel free to send your CV at



    Visitors since Oct, 2015

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Dr. Nupam Mahajan


Nupam Mahajan, PhD.
Associate Professor
Moffitt Cancer Center

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


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

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

Comprehensive Melanoma Research Center

Pardee Foundation

Miles for Moffitt, 2009 & 2015