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
- 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
- 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.
Mahajan K et al. J. Cell. Physiol. 224: 327-333,
- WEE1 epigenetic signaling
- Characterization of novel WEE1 and ACK1 small molecule inhibitors
- Role of ACK1/AR signaling in castration resistant prostate cancer
SRB-2, Office # 22043
Moffitt Cancer Center
12902 Magnolia Drive
Tampa, Florida 33612
National Institute of Health (NIH)/NCI-RO1
Department of Defense (DoD); 2012, 2013 & 2015
Comprehensive Melanoma Research Center
Miles for Moffitt; 2009 & 2015