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　　报告题目： Modeling aneuploidy as a mechanism to escape targeted cancer therapy

　　报 告 人：Robert Benezra, Ph.D.

　　Professor，Cancer Biology and Genetics Program

　　Memorial Sloan-Kettering Cancer Center

　　时    间：2011年6月1日（星期三）上午10：00

　　地    点：医学部逸夫楼509

　　主 持 人：尹玉新教授

　　报告人简介：

　　Dr. Robert Benezra is the member of Cancer Biology and Genetics Program in Memorial Sloan-Kettering Cancer Center. Dr. Robert Benezra received his PhD at Columbia University in the laboratory of Dr. Richard Axel where he studied the chromatin structural changes that accompany gene activation in higher and lower eukaryotes. As a postdoctoral fellow at the Fred Hutchinson Cancer Center with Dr. Harold Weintraub, Dr. Benezra identified, in 1990, the Id proteins as naturally occurring dominant negative antagonists of the basic helix-loop-helix family of transcription factors. In his own lab he has gone on to show the importance of these proteins in stem cell self-renewal, tumor initiation and progression and angiogenesis. In 1996, Dr. Benezra identified the first human mitotic checkpoint gene, hsMad2, and demonstrated its importance in the inhibition of the metaphase-to-anaphase transition in every cell cycle. More recent work has shown that overexpression of Mad2 is hard wired into tumor suppressor loss which in turn leads to the acquisition of aneuploidy and resistance to targeted therapies in mouse models. Dr. Benezra’s lab continues to shed light on important basic biological principles which underlie tumorigenesis, metastasis and tumor stromal cell interactions.

　　Representative Publication:

　　1. Mad2-induced chromosome instability leads to lung tumour relapse after oncogene withdrawal.

　　Sotillo R, Schvartzman JM, Socci ND, Benezra R. Nature. 2010 Mar 18; 464(7287):436-40.

　　2. Mitotic chromosomal instability and cancer: mouse modelling of the human disease.

　　Schvartzman JM, Sotillo R, Benezra R. Nat Rev Cancer. 2010 Feb; 10(2):102-15. Review.

　　3. Very CIN-ful: whole chromosome instability promotes tumor suppressor loss of heterozygosity. Sotillo R, Schvartzman JM, Benezra R. Cancer Cell. 2009 Dec 8; 16(6):451-2.

　　4. Hec1 overexpression hyperactivates the mitotic checkpoint and induces tumor formation in vivo. Diaz-Rodríguez E, Sotillo R, Schvartzman JM, Benezra R. Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16719-24.

　　5. Peptide-conjugated antisense oligonucleotides for targeted inhibition of a transcriptional regulator in vivo. Henke E, Perk J, Vider J, de Candia P, Chin Y, Solit DB, Ponomarev V, Cartegni L, Manova K, Rosen N, Benezra R. Nat Biotechnol. 2008 Jan; 26(1):91-100.