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