Translational Medicine, Signal Transduction, Biochemistry, Molecular Biology, Cell Biology.
- The Regulation of Chromosomal Instability in Colorectal Cancer Progression
- Rewired Signaling of Colorectal Cancer with BRAF Mutations and Potential Targeting Therapeutic Strategies
RESEARCH ACTIVITIES & ACCOMPLISHMENT
I am fascinated by signaling circuitry underlying the pathogenesis of cancer, with an emphasis on the oncogenic and metabolic signaling network and its implication in personalized molecular targeted therapy.
AMPK, an energy sensor, attenuates BRAF-MEK-ERK pathway leading to cell growth suppression. This crosstalk between metabolic and mitogenic pathways suggests a strategy for preventing the development of cSCCs (cutaneous squamous cell carcinomas) associated with BRAF-targeted therapy by activation AMPK. The pre-clinical tests showed that combining phenformin, an AMPK activator, with a BRAFi results in enhanced efficacy compared with either agent alone in both in vitro and in vivo models of BRAF mutant tumors.
Regulation of BRAF signaling by AMPK. (Shen, et. al., Mol. Cell. 2013)
Stag2, a tumor suppressor, is a component of cohesion complex that regulates chromosomal architecture and gene expression. The inactivating mutations in Stag2 promote BRAF-MEK-ERK signaling through CTCF-dependent transcriptional control, which underlies the tumor suppressor role of Stag2 in cancer and contributes to the development of BRAFi resistance in melanoma.
The mechanism of STAG2 regulates ERK signaling. (Shen et. al., Nat. Med. 2016)