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, upstream of major histone loci Hist1.
  • H2B Tyr37-phosphorylation suppressed transcription of all the core and linker histones, thus maintaining equimolar ratio of DNA to histones before cells enter mitosis.
  • We demonstrated that ACK1 (also known as TNK2) activation is present in various tumors, including prostate, breast, ovarian and pancreatic cancers.
  • We identified a novel AKT phosphorylation site, Tyrosine 176. AKT Tyr176- phosphorylation correlated with breast and pancreatic cancer progression to metastatic stages.
  • Androgen receptor (AR) was identified to be ACK1 substrate. The Tyr267-phosphorylated AR initiated a distinct trasncriptional program which was critical for androgen-independent growth of prostate cancer (also called as CRPC).
  • Recently, epigenetic regulatory role of ACK1 was identified: ACK1 phosphorylates histone demethylase KDM3A (JHDM2A) at a novel site, Tyr 1114 to regulate the mammary tumor oncogene HOXA1, facilitating tamoxifen-resistant growth of the breast cancer cells.
  • Realizing significance of ACK1 `addiction' of various cancer cells, we have developed a new class of ACK1 small molecule inhibitor, 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-H2B epigenetic signaling in melanoma
    • Characerization of ACK1/TNK2 knockout mice to assess ACK1/AKT signaling
    • Identification of novel WEE1, ACK1 and AKT small molecule inhibitors
    • Role of ACK1/AR signaling in castration resistant prostate cancer

    Postdoctoral Opportunities

    We are currently interested in hiring a postdoctoral fellow and a research associates in our lab, If interested, please send your CV at



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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)

Comprehensive Melanoma Research Center

Pardee Foundation