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We study the cohesin complex and its role in the pathogenesis of cancer. Cohesin is a protein complex discovered in 1997 composed of ~11 known components that "coheres" sister chromatids until it is degraded in mitosis, enabling sister chromatids to separate into the two daughter cells. In 2011 we reported that one component of cohesin known as STAG2 (or SA2) is commonly mutated in human cancer, providing key initial evidence that cohesin inactivation causes cancer. Since then, we and others have discovered frequent mutations of STAG2 and other cohesin genes in a wide range of common human cancers including bladder cancer, Ewing sarcoma, glioblastoma multiforme, and leukemia. Highlighting the importance of STAG2 as a tumor suppressor gene, in 2014 The Cancer Genome Atlas identified STAG2 as one of only 12 genes that are significantly mutated in four or more human cancer types. Initially we thought that cohesin mutation caused cancer by disrupting the normal segregation of chromosomes to daughter cells during mitosis. However, more recently this has been called into question, and we and others now consider it likely that cohesin mutations cause cancer via other mechanisms such as regulating chromatin structure, transcription, and cellular differentiation. Work in our lab focuses on better understanding the functions of cohesin in both normal and neoplastic cells.

Todd Waldman

Todd Waldman MD, PhD
Professor of Oncology
Director, MD/PhD Program
Georgetown University School of Medicine
Lombardi Comprehensive Cancer Center
3970 Reservoir Road, NW
NRB E304
Washington, DC 20057
(202) 687-1340

Curriculum Vitae
(updated July 2017)

 

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