Tianyan Gao, PhD

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. 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. Cancer metabolism is another research focus of my laboratory. We are interested in determining the molecular mechanism by which adipocytes in the tumor microenvironment promote tumorigenesis and progression. Despite being one of the major components in the tumor microenvironment, relatively few studies have rigorously examined the role of adipocytes in colon cancer. We discovered that cancer associated adipocytes not only secrete pro-inflammatory cytokines, but also release abundant fatty acids that can be taken up by the cancer cells. This uptake of fatty acids allows the cancer cells to become more resistant to energy stress by enhancing mitochondrial fatty acid oxidation; and the presence of adipocytes promotes cancer stem cell properties. In addition, we are actively investigating the role of mitochondrial metabolism in regulating cell signaling and tumorigenesis in colon cancer.