Indiana University Melvin and Bren Simon Cancer Center

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Hematopoiesis, Malignant Hematology, Immunology Research Program

The Hematopoiesis, Malignant Hematology, Immunology Research Program has three themes:

1. Normal Hematopoietic Stem/Progenitor Cell Characteristics Cells from normal marrow, mobilized blood, and cord blood are evaluated for genes, receptors, proliferation, self-renewal, survival/apoptosis, differentiation, and migration/homing/mobilization

2. Malignant Hematology Mechanistic insight into the growth of cancer/leukemia stem cells and other hematopoietic cells from patients with leukemia, lymphoma and myeloma are evaluated, and means to use this information for modifying preclinical and clinical treatments for patient advantage are undertaken in animal models of disease and in investigator-initiated clinical trials

3. Immunology of stem cell transplantation, immune cell activity and tumor immunology

Understanding the functional capabilities of normal and leukemic hematopoietic stem and progenitor cells, and immune cells and their regulation by cytokines/chemokines and stromal cells, will allow us to design novel procedures to treat cancer and to protect and accelerate recovery of normal hematopoietic and immune cells after intensive conditioning regimens with and without stem cell transplantation. Modification of the microenvironment and of surface proteins/receptors, intracellular molecules, and cytokines/chemokines through up- or down-modulation or deletion will increase our knowledge of the roles these proteins play in regulation.

We use a multidisciplinary approach to understand the basic biology of normal and leukemic blood cell production, the ability of leukemia cells to resist chemotherapy and immunology, and aspire to translate this new information in a timely fashion to the clinic. This program has already produced a number of innovative clinical modalities, including:

• cord blood transplantation, mobilization, and homing of stem cells
• identification of new activities for cytokines/chemokines and the means to accelerate recovery of normal blood cells after hematopoietic stem cell transplantation and chemotherapy and irradiation
• the use of new drugs to reverse resistance to chemotherapy