Research

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Charles M.  Roberts, MD, PhD

Charles Roberts
Lab:
Roberts Laboratory
Research Center:
Dana-Farber/Boston Children’s Cancer and Blood Disorders Center
Department:
Medicine Research
Division
Hematology/Oncology Research
Hospital Title:
Principal Investigator
Academic Title:
Associate Professor, Harvard Medical School
Research Focus Area:
Altered chromatin remodeling and epigenetics in cancer
Contact:
617-632-5297
Contact Via Email
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Research Overview

Visit The Charles Roberts Lab

My laboratory is interested in the role of dysfunctional chromatin remodeling in the genesis of cancer. It is increasingly clear that epigenetic modifications play a critical role in the development of cancer. The Swi/Snf complex, which utilizes ATP hydrolysis to remodel chromatin, has a potent role in the genesis of cancer. At least six SWI/SNF subuntis have recently been found to be recurrently and frequently mutated in a variety of human cancers, including in highly pediatric cancers called malignant rhabdoid tumors as well as in substantial subsets of lung, breast, prostate, colorectal, ovarian, pancreas, stomach, liver, kidney, and bladder cancers. Accumulating evidence has linked the Swi/Snf complex to both human cancer and other tumor suppressor pathways indicating that the complex has diverse roles in growth regulation and tumor suppression. Indeed, wWe have recently demonstrated the functional significance of these mutations by generating mice carrying conditional mutations in a key role for Snf5, a core member of this complex, and finding that 100% of these mice develop cancer, with a median onset of only 11 weeks. This rate is remarkably rapid for the inactivation of a single gene, and is indeed twice as fast as P53 deficient mice develop cancer. in tumor suppression in a novel mouse model. Inactivating mutations in the SNF5 gene result in aggressive cancers in children and a familial cancer predisposition syndrome.We are now focused upon elucidating the mechanism by which mutation of SWI/SNF subunits drives cancer growth with a goal of identifying new ways to therapeutically intervene in these cancers. We hypothesize that Snf5 is a master regulator of gene expression via its effects on chromatin structure and seek to identify the mechanisms by which perturbation of this ATPase chromatin remodeling complex leads to cancer formation. Given the dramatic nature in which inactivation of Snf5, leads to cancer formation, cComplete characterization of this complex will lead to insights into tumorigenesis and may should identify further suggest novel therapeutic strategies. Thus, we are using mouse modeling, molecular biological, and biochemical approaches to characterize this newly appreciated mechanism of tumor suppression.

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Related Laboratory

Roberts Laboratory

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RELATED RESEARCH CENTER

Dana-Farber/Boston Children’s Cancer and Blood Disorders Center

Dana-Farber/Boston Children's Cancer and Blood Disorders Center is one of the top research centers in the world for pediatric cancers and blood diseases. It brings together laboratory scientists and clinical researchers from Dana-Farber Cancer Institute and Boston Children’s Hospital in a single program. We investigate pediatric cancers and non-malignant blood disorders from every angle—from examining cells under the microscope to tracking the effectiveness of current drug regimens using the most advanced molecular methods—so that we can create better treatments for children seen here and around the world.

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