Hematologic Malignancies Program (HMP)

Overview

The overall scientific goal of the Hematologic Malignancies Program (HMP) is to understand the molecular basis of hematologic malignancies and their resistance to therapy, and to apply this information to develop novel preventive, diagnostic, and therapeutic strategies. The program is broadly divided into four major research areas: lymphoid malignancies, myeloid malignancies, multiple myeloma, and stem cell transplantation. The current major research themes are:

  1. Role of signaling pathways, especially the NF-κB pathway, in lymphoid malignancy pathogenesis and resistance to therapy. Research in this area includes: a) regulation of the classical (canonical) and alternate (non-canonical) NF-κB pathways, b) mechanisms by which the classical and alternate NF-κB pathways get up-regulated in lymphoid malignancies associated with viral infections, c) contributions of the classical and alternate NF-κB pathways to lymphoid malignancies not associated with viral infections, d) development of agents targeting the NF-κB pathway for treatment of lymphoid malignancies, and e) NF-κB as a predictive marker of treatment response in lymphoid malignancies.
  2. Role of bone microenvironment-dependent and -independent factors in the pathogenesis of myeloma (including myeloma bone disease), and resistance to therapy. Research in this area focuses on: a) signaling pathways involved in myeloma pathogenesis, b) role of bone micro-environmental factors in myeloma development, c) pathogenesis and treatment of myeloma bone disease, and d) new drug development for myeloma.
  3. Signaling pathways involved in the pathogenesis of myeloid malignancies and in resistance to therapy. Research focuses on studying the role of: a) Src and ERK family kinases in myeloid differentiation and development of AML, b) Src family kinases in the pathogenesis of CML, c) NPM-RAR in the pathogenesis of Acute Promyelocytic Leukemia (APL), and d) genetic and epigenetic alterations contributing to drug resistance in myeloid malignancies.
  4. Hematopoietic stem cell biology and strategies to improve the outcome of hematopoietic stem cell transplantation. These studies include: a) delineation of the inflammatory signaling pathways during the early phase of graft-versus-host disease (GVHD) with the aim of developing targeted approaches that can reduce the transplantation-induced inflammatory reaction and thereby prevent the development of GVHD, b) mechanism(s) by which donor lymphocyte infusions induce graft-versus-leukemia (GVL) effect and development of strategies to enhance GVL effect, c) identification of minor histocompatibility antigens in order to achieve a more selective targeting of host hematopoietic cells by GVL effect, and d) hematopoietic stem cell biology.