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[lecture]-The Merlin-Hippo Signaling Network in Contact Inhibition and Tumor Suppression

报告人:Filippo G. GiancottiProfessor.

主持人:高绍荣教授

时间:2015年12月8日星期二上午10:00-11:30

地点:医学大楼2楼报告厅

Research Focus
 Filippo’s research as a graduate student with Guido Tarone and Paolo Comoglioin Torino, and later as a postdoctoral fellow with ErkkiRuoslahti, contributed to the identification of the fibronectin receptor (integrin a5b1) and the demonstration that it possesses a signaling function. His laboratory at NYU elucidated key signaling pathways activated by integrins and started to define their role in cancer cells in vitro. At Memorial Sloan-Kettering Cancer Center, they introduced in mice mutations in integrins and integrin signaling components and obtained evidence that integrin signaling is required for both tumor initiation and progression. In addition, they elucidated the mechanism by which Merlin/NF2 mediates contact inhibition and suppresses tumorigenesis. Recently, they developed novel forward genetic screens in the mouse that enable the identification of genes that enforce metastatic dormancy and of genes that promote metastatic reactivation.


Positions and Employment
 2004- pres. Member (with Tenure), Cell Biology Program, SKI, MSKCC, NY; Professor, Cornell University of Graduate School of Medical Sciences, NY; Professor, Gerstner Sloan-Kettering Graduate School of Biomedical Sciences, NY.
 2000-2004 Member (with Tenure), Cellular Biochemistry and Biophysics Program, SKI, MSKCC, NY; Professor, Cornell University of Graduate School of Medical Sciences, NY.
 1996- 2000 Associate Member, Cellular Biochemistry and Biophysics Program, Sloan-Kettering Institute (SKI), Memorial Sloan-Kettering Cancer Center (MSKCC), NY
 1991-1996 Assistant and Associate Professor, Department of Pathology, NYU School of Medicine, NY


Selected Publications
 1. Okada T*, Esposito I*, Sinha S*, Schiavon G, Lopez-Lago MA, Su W, Pratilas CA, Abele C, Hernandez J, Ohara M, Okada M, Viale, A, Heguy A, Sapino A, Seshan VE, Long S, Inghirami G, Rosen N, GiancottiFG. Inactivation of the Rho-GTPase Rnd1 induces neoplastic conversion and EMT by activating Ras Signaling in aggressive subtypes of breast cancer. Nat. Cell Biol. 2015.
 2. Li W, Cooper J, Zhou L, Yang C, Erdjument-Bromage H, Zagzag D, Snuderl M, Ladanyi M, Hanneman O, Zhou P, Karajannis M, Giancotti FG.  Merlin/NF2 loss-driven tumorigenesis linked to CRL4DCAF1-mediated inhibition of the Hippo pathway kinases Lats1 and 2 in the nucleus. Cancer Cell 2014.
 3. Yoshioka T*, Otero J*, Chen Y, Kim Y-M, Koutcher JA, Satagopan J, Reuter V, Carver B, de Stanchina E, Enomoto K, Greenberg NM, Scardino PT, Scher HI, Sawyers CL, and Giancotti FG. b4 Integrin signaling induces expansion of prostate tumor progenitors.  J. Clin. Invest.2013.
 4. Gao H, Chakraborty G,Lim AP, Mo Q, Decker M, Vonica A, Shen R, Brogi E, Brivanlou AH, and Giancotti FG.  The BMP inhibitor Coco reactivates breast cancer cells at lung metastatic sites. Cell2012.
 5.  Li W*, You L*, Cooper J, Schiavon G, Pepe-Caprio A, Zhou L, Ishii R, Giovannini M, Hanemann CO, Long SB, Erdjument-Bromage H, Zhou P, Tempst P, Giancotti FG.  Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4DCAF1 in the nucleus. Cell 2010.