The main goal of the Hematologic Malignancies Program is to develop novel molecularly-based therapies to improve the outcome of patients with hematologic system cancers. The philosophy of this program is to promote close collaborations between the laboratory and the clinic, enabling a seamless flow of information in both directions to generate novel hypotheses and rapidly translate laboratory discoveries into clinical applications. This approach is reflected by the program’s emphasis on physician-scientists and disease-focused teams, where clinicians and lab-based scientists closely collaborate.
Three focus groups have been established that concentrate on unique aspects of hematologic malignancies: Hematopoiesis, Leukemogenesis/Lymphomagenesis and HIV/AIDS. The unifying feature of all three focus groups is their reliance on cellular, molecular and genetic approaches to uncover mechanisms of disease pathogenesis and develop therapeutic strategies based on this knowledge.
- The Hematopoiesis Group studies the regulation of normal and leukemic hematopoiesis to identify critical pathways in differentiation and maintenance as potential therapeutic targets for the prevention or treatment of hematologic cancers. Recent discoveries include a previously unrecognized role for TNF in the progression of FA to acute myeloid leukemia (AML) and the development of a novel and unique assay to screen for inhibitors of the FA pathway.
- The Molecular Leukemogenesis/Lymphomagenesis Group is interested in the genetic abnormalities and signaling pathways that lead to malignant transformation of hematopoietic cells, with a view of exploiting this information for molecularly targeted therapy. Members have been instrumental in developing imatinib (Gleevec) as the standard of care for the treatment of chronic myeloid leukemia (CML). They have made significant contributions toward unraveling mechanisms of imatinib resistance and the subsequent development of second and third-line inhibitors to treat patients with imatinib failure, and they have helped to extend the imatinib paradigm to hematologic cancers other than CML.
- The Virology Group investigates the mechanisms by which viral pathogens lead to lymphomagenesis and immunosuppression in cancer patients. The Virology focus group is interested in oncogenic viruses, specifically in the mechanisms by which they escape the host’s immune response and how they lead to cellular transformation in specific tissues. A recent discovery by this group is that the HIV Viral Infectivity Factor (VIF) induces the degradation of APOBEC3G and APOBEC3F, cytidine deaminases that are crucial antiviral pathways in T cells, suggesting that re-establishing the function of these proteins may be a promising therapeutic strategy.
|William H. Fleming, M.D., Ph.D|