My lab focuses on elucidating the functional importance of a novel family of protein phosphatase, PHLPP, in regulating tumorigenesis. We use colon cancer as a model system to study how PHLPP functions in suppressing cancer development and progression. PHLPP represents a family of novel Ser/Thr protein phosphatases that directly dephosphorylates Akt and terminates Akt-mediated growth and survival signals.
The long-term goal of my lab is to understand the physiological function of PHLPP and the molecular mechanisms underlying PHLPP-mediated regulation in cancers. In addition, we have developed PHLPP knockout mouse models in our lab to further investigate the physiological role of PHLPP. The results from our studies will aid in developing novel therapeutic strategies in cancer treatment by using PHLPP as a target.
- Loss of PHLPP expression in colon cancer: Role in proliferation and tumorigenesis. Liu J, Weiss HL, Rychahou PG, Jackson LN, Evers BM, and Gao T. Oncogene 28:994-1004, 2009.
- β-TrCP-mediated ubiquitination and degradation of PHLPP1 is negatively regulated by Akt. Li X, Liu J, and Gao T. Mol Cell Biol 29(23):6192-205, 2009.
- Scribble-mediated membrane targeting of PHLPP1 is required for its negative regulation of Akt. Li X, Yang H, Liu J, Schmidt MD, Gao T. EMBO Rep 12:818-2, 2011.
- PHLPP-mediated dephosphorylation of S6K1 inhibits protein translation and cell growth. Liu J, Stevens PD, Li X, Schmidt MD, Gao T. Mol Cell Biol 31(24):4917-2, 2011.
- The deubiquitination enzyme USP46 functions as a tumor suppressor by controlling PHLPP-dependent attenuation of Akt signaling in colon cancer. Li X, Stevens PD, Yang H, Gulhati P, Wang W, Evers BM, Gao T. Oncogene 32:471-478, 2013.