遗传工程国家重点实验室青年学术报告 余发星
遗传工程国家重点实验室青年学术报告
题目:The Hippo Pathway: Regulation and Implications in Cancer

报告时间:16日下午1330

地点:邯郸校区逸夫科技楼会议室1

 

报告人:

FAXING YU (余发星), Ph.D.

Department of Pharmacology and Moores Cancer Center,

University of California San Diego

 

 

The Hippo pathway is crucial in animal development and tissue homeostasis by regulating cell proliferation, death, and differentiation. However, upstream signals that regulate the mammalian Hippo pathway have remained elusive until recently.  In this talk, I will discuss the regulation of the Hippo pathway by G-protein-coupled receptor (GPCR) signaling. Serum-borne lysophosphatidic acid (LPA) and sphingosine 1-phosphophate (S1P) act through G12/13-coupled receptors to inhibit the Hippo pathway kinases Lats1/2, thereby activating YAP/TAZ transcription coactivators. Furthermore, activation of YAP/TAZ is involved in LPA-induced gene expression, cell migration, and proliferation. In contrast, stimulation of Gs-coupled receptors by glucagon or epinephrine activates Lats1/2 kinase activity, thereby inhibiting YAP/TAZ function. Thus, GPCR signaling can either activate or inhibit the Hippo-YAP pathway depending on the coupled G protein. Dysregulations of GPCR signaling frequently occur in human cancers; for instance, an activating mutation of Gq or G11 is present in approximately 80% uveal melanomas (UM) -- the most common cancer of the eye in adults. These mutant Gq and G11 are able to stimulate YAP/TAZ activity, and YAP/TAZ are potently activated in UM cell lines and UM clinical specimens with Gq/11 mutation. The hyperactivation of YAP/TAZ by dysregulated GPCR signaling may contribute to development of UM and other types of human cancers.

 

Education and research experience:

10.7-prest   Postdoctoral Training, University of California San Diego, La Jolla, USA.

Supervisor: Kun-Liang Guan, Ph.D.

10.2-10.7    Postdoctoral Training, Institute of Molecular and Cell Biology, Singapore.

Supervisor: Yan LUO, Ph.D.

06.7-10.2    Ph.D., Biochemistry, National University of Singapore, Singapore

Institute of Molecular and Cell Biology, Singapore

Supervisor: Yan LUO, Ph.D.

2000-2004   B.S., Biochemistry (Honors), National University of Singapore, Singapore

 

5 Most Significant Publications:

1. Yu FX, Guan KL. The Hippo pathway: regulators and regulations. Genes Dev. 2013 Feb 15;27(4):355-71 (Invited review).

2. Yu FX, Zhang Y, Park HW, Jewell JL, Chen Q, Deng Y, Pan D, Taylor SS, Lai ZC, Guan KL. Protein Kinase A activates the Hippo pathway to modulate cell proliferation and differentiation. Genes Dev. 2013 Jun 1;27(11):1223-32.

3. Yu FX, Zhao B, Panupinthu N, Jewell JL, Lian I, Wang LH, Zhao J, Yuan H, Tumaneng K, Li H, Fu XD, Mills GB, Guan KL. Regulation of the Hippo-YAP pathway by G-protein coupled receptor signaling. Cell. 2012 Aug 17;150(4):780-91.

4. Yu FX, Goh SR, Dai RP, Luo Y. Adenosine-containing Molecules Amplify Glucose Signaling and Enhance Txnip Expression. Mol Endocrinol. 2009 Jun;23(6):932-42.

5. Yu FX*, Dai RP*, Goh SR, Zheng L, Luo Y. Logic of a mammalian metabolic cycle: An oscillated NAD(+)/NADH redox signaling regulates coordinated histone expression and Sphase progression. Cell Cycle. 2009 Mar 1;8(5): 773-79.
发布日期:2014/1/6