Welcome to the Mahajan Lab Website

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:

ACK1 (TNK2) : An oncogene with novel epigenentic activity in prostate, breast & lung cancers

WEE1 : A novel epigenetic modulator & its significance in various malignancies

ABL1 : A proto-oncogene with nuclear tyrosine kinase activity

 

Some of the major findings of our lab include:

  • We discovered a new epigenetic event, phosphorylation of histone H4 at Tyrosine 88 residue
  • ACK1 kinase deposit pY88-H4 epigenetic marks and thus play a crucial role in progression of prostate cancer to drug-resistant stage
  • We designed and developed a new class of a small molecule inhibitor for ACK1, (R)-9bMS
  • We discovered that WEE1 is an epigenetic kinase that phosphorylate histone H2B at Tyrosine 37, regulating global histone output
  • WEE1 epigenetic activity also regulates IDH2 expression, thus regulating global 5-hmC levels
  • Recently, we performed a screen and have identified a novel class of WEE1 epigenetic inhibitor

 

  • We identified a novel AKT phosphorylation site, Tyrosine 176, that correlated with prostate, breast and pancreatic cancer progression to metastatic stages
  • ACK1 phosphorylates histone demethylase KDM3A (JHDM2A) at Tyrosine 1114 to regulate HOXA1, facilitating tamoxifen-resistance of the breast cancer

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

 

Current Projects

    • ACK1 epigenetic signaling
    • ACK1/TNK2 knockout mice
    • Characterization of novel class of ACK1 inhibitors
    • WEE1 epigenetic signaling
    • Characterization of novel class of WEE1 small molecule inhibitors
    • Role of ACK1-AR signaling in triple negative breast cancer
    • Long non-coding RNAs as chromatin modifiers

Postdoctoral Opportunities

We are in recruitment drive and will hire up to 3 new postdocs. Send your CV to

Nupam.mahajan@moffitt.org

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: