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David M. Weinstock, MD

Assistant Professor, Department of Medicine, Harvard Medical School

Attending Physician, Medical Oncology Service, Dana-Farber Cancer Institute

Contact Info

David Weinstock
Dana-Farber Cancer Institute
450 Brookline Avenue
Boston, MA, 02215
Mailstop: D510B
Phone: 617-632-4245
Fax: 617-632-5167
DavidM_Weinstock@dfci.harvard.edu

Assistant

Not Available.

DF/HCC Program Affiliation

Leukemia
Cancer Genetics

Lab Website

Weinstock laboratory

Research Abstract

Despite decades of effort, the tumor genome remains ripe for discovery. The laboratory utilizes a novel functional screen to identify and characterize oncogene alterations directly from tumor specimens. Newly-identified alterations are further assayed using a variety of in vitro and in vivo methods, with the ultimate goal of translating discoveries into novel therapies.

Our initial efforts identified CRLF2, a previously obscure cytokine receptor, as an essential oncogene in 5-10% of adult and pediatric acute lymphoblastic leukemia (ALL). We subsequently identified somatic mutations within CRLF2 and the kinase JAK2, suggesting that agents targeting JAK2 activity will be effective for patients with ALL dependent on CRLF2. Over the past two years, we have utilized in vitro and in vivo models of CRLF2-dependent signaling to demonstrate that inhibitors of HSP90, which promote the degradation of JAK2, have potent activity against CRFL2-rearranged leukemias. These findings have inspired clinical trials in both children and adults with this poor-risk subset of ALL.

In a second line of inquiry, we are assaying the nature and determinants of DNA repair in mammalian cells. These studies extend from tumor specimens, where we have characterized a novel oncogene-DNA repair interaction, to human embryonic and induced pluripotent cells.

Finally, our laboratory is actively investigating the molecular evolution of somatic alterations in lymphoid malignancies. We utilize ultra-deep sequencing of subpopulations sorted from bone marrow specimens to trace the ontogeny of specific alterations identified within lymphomas. The initial efforts were the first to distinguish early and late mutations in paired lymphomas that developed in a bone marrow transplant donor and recipient several years after transplantation.

Publications

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