, Hematopoiesis and Hematologic Malignancies Program (HHM) Based on the robust basic mechanistic studies performed by our members that resulted in consecutive outstanding scores for the last four NCI site visits, HHM is now a basic science Program whose ultimate goal is to advance treatment of hematologic malignancies and disorders through rigorous basic scientific laboratory efforts. Our goal is to gain mechanistic insight into malignant cell processes, how they differ from normal processes through interactions with the TMM Program, and to provide this information with our guidance to the EDT and CPC programs for translation for clinical utility and health benefit to modulate and slow disease progression, with the ultimate goal of curing malignant diseases. Our Program has two areas of focus: Hematopoiesis (H) and Hematologic Malignancy (HM) themes. The H-theme includes: characterization of human and mouse hematopoietic stem (HSC) and progenitor (HPC) cells and their mechanistic regulation, understanding the biology of cytokine/chemokine actions, including cells of the hematopoietic microenvironment and the immune systems and their interactions that regulate HSC and HPC functions; this includes proliferation, survival, self-renewal, differentiation, mobilization and engraftment for hematopoietic cell transplantation (HCT) and biomarker/biomolecule assessment for predicting and modulating graft vs host disease after HCT without adversely modulating graft vs. leukemia/tumor effects. The HM-theme is focused on understanding and modifying the biology of leukemia/myeloma (including leukemia stem cells) and bone cell interactions (especially for multiple myeloma), including intracellular events mediating the function and interactions of these cells. The Program has two highly interactive co-leaders: Broxmeyer and Roodman, both with national and international reputations and who have a deep and long history of research in hematopoiesis and hematologic malignancies. HHM has a total of 17 Full and 7 Associate interactive members from 6 different Departments of the IU School of Medicine. Our Program members have published 304 papers during the past CCSG funding period, of which 25% are intra-programmatic, 17% are inter-programmatic, and 65% are multi-institutional, with 32% of these publications in journals with an impact factor ranging from 9 to greater than 40. The total (direct cost) of external peer-reviewed funding and NCI funding are respectively $7.6M and $1.17M with the current funding per Full member currently at $448K. The Program also has three NIH T32 Training grants (DK007519, HL007910, and AI060519) at $733.3K, and a U54 Cooperative Center of Excellence in Hematology (DK106846). Our Program has greatly benefited from IUSCC through: pilot-funding, core facilities, sponsored seminar series, cancer grand rounds and with numerous formal and informal intra- and inter-programmatic meetings. Collectively, these have enhanced our capacity for continuing to perform outstanding cutting-edge science, through interactions with the TMM, EDT and CPC Programs and for the translation of this knowledge for health benefits.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Center Core Grants (P30)
Project #
5P30CA082709-21
Application #
9987557
Study Section
Subcommittee I - Transistion to Independence (NCI)
Project Start
1999-09-22
Project End
2024-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
21
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Type
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Huang, Xinxin; Guo, Bin; Liu, Sheng et al. (2018) Neutralizing negative epigenetic regulation by HDAC5 enhances human haematopoietic stem cell homing and engraftment. Nat Commun 9:2741
Serratore, Nina D; Baker, Kortany M; Macadlo, Lauren A et al. (2018) A Novel Sterol-Signaling Pathway Governs Azole Antifungal Drug Resistance and Hypoxic Gene Repression in Saccharomyces cerevisiae. Genetics 208:1037-1055
Hoggatt, Jonathan; Singh, Pratibha; Tate, Tiffany A et al. (2018) Rapid Mobilization Reveals a Highly Engraftable Hematopoietic Stem Cell. Cell 172:191-204.e10
Filley, Anna; Henriquez, Mario; Bhowmik, Tanmoy et al. (2018) Immunologic and gene expression profiles of spontaneous canine oligodendrogliomas. J Neurooncol 137:469-479
Sishtla, Kamakshi; Pitt, Natalie; Shadmand, Mehdi et al. (2018) Observations on spontaneous tumor formation in mice overexpressing mitotic kinesin Kif14. Sci Rep 8:16152
Koh, Byunghee; Abdul Qayum, Amina; Srivastava, Rajneesh et al. (2018) A conserved enhancer regulates Il9 expression in multiple lineages. Nat Commun 9:4803
Reese, Michael J; Knapp, Deborah W; Anderson, Kimberly M et al. (2018) In vitro effect of chlorambucil on human glioma cell lines (SF767 and U87-MG), and human microvascular endothelial cell (HMVEC) and endothelial progenitor cells (ECFCs), in the context of plasma chlorambucil concentrations in tumor-bearing dogs. PLoS One 13:e0203517
Singh, Pratibha; Fukuda, Seiji; Liu, Liqiong et al. (2018) Survivin Is Required for Mouse and Human Bone Marrow Mesenchymal Stromal Cell Function. Stem Cells 36:123-129
Olivos 3rd, David J; Perrien, Daniel S; Hooker, Adam et al. (2018) The proto-oncogene function of Mdm2 in bone. J Cell Biochem 119:8830-8840
Shiue, Kevin; Cerra-Franco, Alberto; Shapiro, Ronald et al. (2018) Histology, Tumor Volume, and Radiation Dose Predict Outcomes in NSCLC Patients After Stereotactic Ablative Radiotherapy. J Thorac Oncol 13:1549-1559

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