B.S. Beijing Medical University, Beijing, China
Ph.D. Northwestern University, Chicago, IL
Postdoctoral fellow, University of California San Diego, La Jolla, CA.
Precise control of the balance between protein phosphorylation and dephosphorylation is critical for living organisms to maintain normal physiological functions. Dysregulation of signaling pathways that results in disturbing this balance can lead to the development of cancer. Numerous studies have focused on the activation processes of signaling pathways, which are often mediated by protein kinases. However, considerably less evidence is available concerning how and when the signals are shut off by protein phosphatases.
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 belongs to a novel family of Ser/Thr protein phosphatases. There are two isoforms, PHLPP1 and PHLPP2, identified in this family. Following our initial discovery of PHLPP as a protein phosphatase and negative regulator of Akt, we have demonstrated that downregulation of PHLPP occurs at high frequency in colon cancer patients, and re-expression of PHLPP in colon cancer cells inhibits cell proliferation in vitro and tumor growth in vivo, thus supporting a tumor suppressor role of PHLPP. In addition, we have discovered that PHLPP is dynamically regulated by protein ubiquitination and deubiquitination in colon cancer, and PHLPP is tightly regulated by a scaffolding protein Scribble.
The long-term goal of my lab is to understand the physiological function of PHLPP and the molecular mechanisms underlying PHLPP-mediated regulation in cancer. To better understand the physiological role of PHLPP in vivo, we have recently developed PHLPP knockout mouse models. We also have a long-standing interest in finding novel substrates of PHLPP. Our studies will aid in developing novel therapeutic strategies in cancer treatment by using PHLPP as a target.