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Tianyan Gao
Assistant Professor
B.S. Beijing Medical University, Beijing, China
Ph.D. Northwestern University, Chicago, IL
Postdoctoral fellow, University of California San Diego, La Jolla, CA.

Office: 859-323-3454
Email: tianyan.gao@uky.edu

Overview ▪ Funding ▪ Recent Publications ▪ PubMed

Positions Available, Graduate Students and Postdocs

Overview
Funding ▪ Recent Publications ▪ PubMed

Colorectal cancer is the second leading cause of cancer-related deaths in the United States with 112,000 new cases diagnosed per year and approximately 52,000 deaths estimated in 2007.
The phosphoinositide-3-kinase (PI3K) signaling pathway has been has been the focus of numerous studies in recent years as mounting evidence has suggested that signaling components in this pathway are critical regulators of mammalian cell proliferation and survival. Hyperactivation of this pathway is often linked with tumor progression and resistance to cancer drug treatment. Serving as the major regulator downstream of PI3K, Akt promotes tumor growth by promoting cellproliferation and inhibiting apoptosis. The activation process of Akt has been studied in great detail. However, little is known about how the signals are turned off once activated. Failure to terminate the growth and survival signals activated by Akt is one of the major mechanisms contributing to hyperactivation in human cancer.

PHLPP represents a family of novel Ser/Thr protein phosphatases that directly dephosphorylates Akt and terminates Akt-mediated growth and survival signals. Our 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. Recently, we found that loss of PHLPP expression is commonly associated with colon cancers and re-introduction of PHLPP into colon cancer cells inhibits tumorigenesis. 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.

Funding
Overview ▪ Recent Publications ▪ PubMed

Our work is funded by National Cancer Institute of NIH and American Cancer Association.

Recent Publications
Overview ▪ Funding ▪ PubMed

1. J. Liu, H. L. Weiss, P. Rychahou, L. N. Jackson, B. M. Evers, and T. Gao (2009) Loss of PHLPP expression in colon cancer: role in proliferation and tumorigenesis. Oncogene 28, 994-1004
2. Qingsong Cai, Jing Li, Tianyan Gao, Jingwu Xie, and B. Mark Evers (2009) PKCδ negatively regulates hedgehog signaling by inhibition of Gli1 activity. J. Biol. Chem. 284: 2150-2158
3. Gao, T., Brognard, J., and Newton, A. C. (2008) The Phosphatase PHLPP Controls the Cellular Levels of Protein Kinase C. J. Biol. Chem. 283: 6300-6311
4. Brognard, J., Sierecki, E., Gao, T., and Newton, A. C. (2007) PHLPP and a second isoform, PHLPP2, differentially attenuate the amplitude of Akt signaling by regulating distinct Akt isoforms. Mol Cell 25: 917-931
5. Tianyan Gao and Alexandra C. Newton (2006) Invariant Leu preceding turn phosphorylation motif controls the interaction of protein kinase C with Hsp70. J. Biol. Chem. 281: 32461 – 32468
6. Tianyan Gao, Frank Furnari and Alexandra C. Newton (2005) PHLPP: a Phosphatase that Directly Dephosphorylates Akt, Promotes Apoptosis, and Suppresses Tumor Growth. Mol. Cell 18: 13-24
7. Erica Dutil Sonnenburg, Tianyan Gao, and Alexandra C. Newton (2001) The phosphoinositide dependent kinase, PDK-1, phosphorylates conventional protein kinase C isozymes by a mechanism that is independent of phosphoinositde-3-kinase. J. Biol. Chem. 276: 45289-45297
8. Tianyan Gao, Adolfo E. Cuadra, Hong Ma, Moritz Bünemann, Brian L. Gerhardstein, Tong Cheng, Robert Ten Eick, and M. Marlene Hosey C-terminal Fragments of the α1C (CaV1.2) Subunit Associate with and Regulate L-type Calcium Channels Containing C-terminal-truncated α1C Subunits. J. Biol. Chem. 276: 21089-21097
9. Tianyan Gao, Alex Toker and Alexandra Newton (2001) The Carboxyl-terminus of protein kinase C provides a switch to regulate its interaction with the phosphoinositide-dependent kinase, PDK-1. J. Biol. Chem. 276, 19588-19596
10. Tianyan Gao and M. Marlene Hosey (2000) Association of L-type Calcium Channels with a Vacuolar H+-ATPase G2 Subunit. Biochemical and Biophysical Res. Comm. 277: 611-616
11. Tianyan Gao, Moritz Bünemann, Brian L. Gerhardstein, Hong Ma and M. Marlene Hosey (2000) Role of the C-terminus of the α1C (Cav1.2) subunit in membrane targeting of cardiac L-type calcium channels. J. Biol. Chem. 275: 25436-25444
12. Brian L. Gerhardstein, Tianyan Gao, Moritz Bünemann, Tipu Puri, Adam Adir and M. Marlene Hosey (2000) Proteolytic processing of the C-terminus of the α1C subunit of L-type calcium channels and the role of a proline-rich domain in membrane-tethering of proteolytic fragments. J. Biol. Chem. 275: 8556-8563
13. Moritz Bünemann, Brian L. Gerhardstein, Tianyan Gao, and M. Marlene Hosey (1999) Functional Regulation of L-type Calcium Channels via Protein Kinase A-mediate Phosphorylation of the β2 Subunit. J. Biol. Chem. 274: 33851-33854.
14. Tianyan Gao, Andy J. Chien and M. Marlene Hosey (1999) Complexes of the α1C and β subunits generate the necessary signal for membrane targeting of class C L-type calcium channels. J. Biol. Chem. 274:2137-2144
15. Andy J. Chien, Tianyan Gao, Edward Perez-Reyes and M. Marlene Hosey (1998) Membrane targeting of L-type calcium channels: Role of palmitoylation in the subcellular localization of the β2a subunit. J. Biol. Chem. 273: 23590-23597
16. Tianyan Gao, Tipu Puri, Brian L. Gerhardstein, and M. Marlene Hosey (1997) Identification and Subcellular Localization of the Subunits of L-type Ca Channels and Adenylyl Cyclase in Cardiac Myocytes. J. Biol. Chem. 272, 19401-07
17. Tianyan Gao, Atsuko Yatani, Mark L. Dell’Acqua, Hidenori Sako, Stuart A. Green, Nathan Dascal, John D. Scott, and M. Marlene Hosey (1997) Cyclic AMP-dependent regulation of cardiac L-type calcium channels requires membrane targeting of protein kinase A and phosphorylation of channel subunits. Neuron 19, 185-196.