Human Oncology and Pathogenesis Program
Memorial Sloan Kettering Cancer Center
The Levine Lab Studies how epigenetic mutations contribute to cancer development and whether there are specific therapies that can be used to target human malignancies with mutations in epigenetic regulators for patients with myeloproliferative neoplasm and acute myeloid leukemia.
The lab continues to investigate these important areas, and hopes to translate this work into novel therapies for leukemia patients and to extend these results to solid tumor patients whose tumors are driven by mutations in epigenetic regulators.
Ross Levine, MD, is a member of the Human Oncology and Pathogenesis Program and the Leukemia Service, Department of Medicine, a professor of medicine at Weill Cornell Medical College, the Laurence Joseph Dineen Chair in Leukemia Research, a core member of the MSK Center for Epigenetics Research, and the director of the MSK Center for Hematologic Malignancies. Dr. Levine received his AB from Harvard College and a M.D. from Johns Hopkins. Dr. Levine served as a Resident in Internal Medicine at the MGH and subsequently as a Hematology-Oncology Fellow at DFCI. He then joined Gary Gilliland’s laboratory as a postdoctoral fellow and performed kinome sequencing at the Broad Institute to identify JAK2V617F and MPL mutations in MPN patients. Their subsequent work included genomic and functional studies of mutant JAK2/MPL disease alleles during his fellowship training. In September 2007 he was recruited to MSKCC to the Human Oncology and Pathogenesis Program while he sees patients on the Leukemia Service. His laboratory focuses on the role of alterations in signaling and in epigenetic regulation in oncogenic transformation and therapeutic response. He serves on the editorial board of Blood, JCI, Haematologica (Associate Editor), and Clinical Cancer Research and on the Medical and Scientific Advisory Board of the Leukemia and Lymphoma Society. He has earned a Scholar Award from the Leukemia and Lymphoma Society, a Young Investigator Award from the American Society of Clinical Oncology, a Scholar Award from the American Society of Hematology, and a Clinical Scientist Development Award from the Doris Duke Charitable Foundation. In 2011 he was elected to the American Society of Clinical Investigation, and was the recipient of the Boyer Award for Clinical Investigation from MSKCC.
“Targeting Mutated Epigenetic Modifiers in Human Malignancies”
Recent genetic studies of human cancer have identified a novel class of mutations that are among the most common mutations observed across different tumor types. These mutations occur in genes that regulate the epigenome, the normal process by which different cell types can express different genes despite having identical DNA sequence homology. These mutations alter the cancer epigenome, predominantly by leading to changes in how DNA is packaged and which genes are expressed in cancer cells.
“Receipt of this award means a lot to me and to the lab. It will allow us to take risks at defining new concepts in cancer biology, and in developing new treatments for cancer patients. This is very important to us.”
We have initiated efforts to understand how these mutations contribute to cancer development, and whether there are specific therapies that can be used to target human malignancies with mutations in epigenetic regulators. These efforts include studies of primary patient samples, development of novel mouse models of human cancers, and preclinical treatment studies to identify and validate new therapeutic approaches. In this proposal we aim to assess whether how mutations in specific epigenetic proteins contribute to human cancer, and to probe these mutated cancers for specific vulnerabilities that can be attached with novel drugs. Although outside the scope of this proposal, our long-term goal is to use the studies in this proposal to inform mechanism based clinical trials that can be used to improve outcomes for cancer patients.
“Innovation means asking difficult questions without easy answers, pushing our knowledge to new area, and trying new approaches to solve important questions.”