The Weinstock laboratory uses a variety of in vitro and in vivo techniques to identify and target novel oncogene alterations directly from hematologic malignancies and elucidate mechanisms of aberrant DNA repair within malignant and nonmalignant stem cells.
Identifying and targeting vulnerabilities in lymphoid neoplasms. The Weinstock laboratory, which currently includes ~25 students, fellows and professional scientists, established a functional screen to identify mutated genes directly from tumors that can promote proliferation and survival in cells. Among our discoveries with that approach was that the cytokine receptor CRLF2 is altered in about 5-10% of acute lymphoblastic leukemia (ALL) cases. We went on to show that CRLF2 alterations confer a poor prognosis, that they results from a specific mechanism of DNA breakage and repair, and that they activate multiple pathway of signaling in the cancer cell. We subsequently identified mutations of G-protein beta subunits across a range of different cancers that drive transformation and resistance to kinase inhibitors. Recently, we defined the biology of a rare subtype of follicular lymphoma, established a clinicogenetic prognostic model for follicular lymphoma, co-developed a strategy to define therapeutic sensitivity of single leukemia cells, and demonstrated the potential for next-generation lymphoma diagnostics in sub-Saharan Africa. Work from our lab has led to 5 clinical trials that are currently open or under review by the SRC/IRB. I lead a Specialized Center for Research (SCOR) that includes DFCI, Memorial Sloan-Kettering Cancer Center and Weil Cornell Medical College, along with additional affiliated centers (City of Hope, Nebraska, Stanford, University of Miami, Fred Hutchinson Cancer Research Center, Washington University) that is focused on developing new strategies to target T-cell lymphomas.