ABSTRACT, Hematopoiesis and Hematologic Malignancies (HHM) Research Program The HHM Research Program is a dynamic basic science research program built on robust collaborations to catalyze impactful research. The Program is devoted to mentoring new faculty to become experts in the field, nourishing diversity of team members, and supporting IUSCCC efforts in the community. In the current grant period, Theme 1, Hematopoiesis, aimed to understand the mechanistic regulation of hematopoietic stem cells (HSCs) and progenitor cells (HPCs), enhance mobilization of HSCs and HPCs for better transplant engraftment, and identify novel biomarker and therapeutic targets to modulate Graft vs. Host Disease (GvHD). Theme 2, Hematological Malignancies, aimed to clarify the cellular processes and intracellular signaling that drive the biology of hematologic malignancies and to better understand the relationship between hematologic malignancies and their bone microenvironment. Significant advances were made in that period. To support IUSCCC's mission to lift the burden of cancer in Indiana and with additional recently recruited translational scientists, we have developed a strategic plan to transition to a translational research program over the next grant period. The Program's long-term goal is to advance treatment of hematologic malignancies through rigorous discoveries that will lead to novel biomarkers and therapeutics. While our overall themes remain the same, we have modified our Specific Aims to incorporate translational components. For Theme 1, Aim 1 is to identify the cell intrinsic and microenvironmental-mediated mechanisms involved in regulating the self-renewal and differentiation of normal and transformed hematopoietic stem and progenitor cells (HSPCs), and Aim 2 is to define the mechanisms involved in enhancing HSPCs' survival as well as decreasing treatment-related toxicity (in particular GvHD) in the therapeutic strategies involving HSCs. For Theme 2, Aim 3 is to determine the intrinsic and extrinsically mediated mechanisms used by hematologic malignancies to enhance their survival and confer resistance to treatment, and Aim 4 is to characterize the immunobiology of hematologic malignancies and utilize this understanding to develop novel therapeutic approaches. The Program has two complementary and interactive co-leaders: Drs. Kapur and Salman. Dr. Kapur brings particular expertise to Theme 1, and Dr. Salman to Theme 2. The Program has 17 Full and 10 Associate members who published 306 papers during the current grant period (24% intra-programmatic, 25% inter-programmatic, 53% multi-institutional), with 34% in journals with IF>10. HHM total external peer-reviewed funding and NCI funding (direct costs) are $5.54M and $2.0M, respectively. The Program also has three training grants (two T32 training grants and a U54 Cooperative Center of Hematology) and is deeply involved in IUSCCC CRTEC efforts. Multiple HHM members are involved in IUSCCC's Office of Com...