The overall goal of this program is to understand and correct, at the molecular level, genetic diseases affecting cells derived from pluripotent hematopoietic stem cells. We believe that to attain this goal, we must understand basic biological processes that affect hematopoietic stem cell behavior both in vitro and in vivo in a basic science laboratory to clinical trial translational effort. The proposed Center of Excellence in Molecular Hematology (CEMH) membership in this application draws from a group of well funded investigators with a diverse but complementary experience in hematopoiesis and stem cell biology, viral mediated gene transfer, molecular genetics, virology, hematopoietic stem cell transplantation (cord blood, bone marrow, and cytokine/reagent mediated mobilization), neonatology and vascular and developmental biology. This group is highly collaborative and interactive with numerous co-authored publications, as well as funded projects that span basic, translational, and clinical research. The Cores proposed in this CEMH submission have evolved and been adapted to the current needs of this program. These include: Flow Cytometry, Animal, Imaging, and Angeogenesis/Endothelial/Proangiogenic Cores. All Cores will support the basic and translational studies that underlying the mission of the CEMH and will facilitate development of new discoveries into human trials. The program also includes a Pilot and Feasibility Project, to be funded in part through University funds in order to enhance the training of young investigators to enhance their ability to successfully compete for extramural (e.g. NIH) funding. Together, the CEMH represents an important assembly of critical cores needed to continue and enhance the basic work in progress and to put in place, support which we believe will be needed over the next five years. TABLE OF CONTENTS OVERALL DESCRIPTION 2 OVERALL CENTER CRITIQUE 3 CENTER DIRECTOR 5 OVERALL COMMITTEE BUDGET RECOMMENDATIONS 5 OVERALL ACTION 5 SUPPORT TO BE NEGOTIATED 5 RESEARCH BASE... 5 ADMINISTRATIVE CORE: Hal E. Broxmeyer, Ph.D., Edward F. Srour, Ph.D ... 9 CORE 1: FLOW CYTOMETRY SERVICES: Edward F. Srour, Ph.D. ... 10 CORE 2: OPTICAL MICROSCOPY: Kenneth Dunn, Ph.D, Nadia Carlesso, MD, Ph.D. ... 14 CORE 3: EXPERIMENTAL MOUSE RESOURCES: Simon Conway, Ph.D, Karen E. Pollock, Ph.D.... 16 CORE 4: ANGIOGENESIS, ENDOTHELIAL, &PROANGIOGENIC CELLS: Mervin C. Yoder, M.D, Jamie Case, Ph.D..... 18 PILOT AND FEASIBILITY (P&F) PROGRAM: Hal E. Broxmeyer, Ph.D., Edward F. Srour, Ph.D 20

Public Health Relevance

Members of the proposed Center of Excellence in Molecular Hematology (CEMH) are at the forefront of innovative basic and clinical research in hematopoiesis and stem cell biology. The establishment of a CEMH will undoubtedly advance the research programs of these investigators and enable cutting edge science in defining mechanisms of molecular regulation of hematopoiesis and stem cell fate.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
1P30DK090948-01
Application #
8051247
Study Section
Special Emphasis Panel (ZDK1-GRB-G (O3))
Program Officer
Bishop, Terry Rogers
Project Start
2010-09-30
Project End
2015-06-30
Budget Start
2010-09-30
Budget End
2011-06-30
Support Year
1
Fiscal Year
2010
Total Cost
$739,912
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Alvarez, Marta B; Xu, LinLin; Childress, Paul J et al. (2018) Megakaryocyte and Osteoblast Interactions Modulate Bone Mass and Hematopoiesis. Stem Cells Dev 27:671-682
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; Alvarez, Marta; Cheng, Ying-Hua et al. (2017) Lnk Deficiency Leads to TPO-Mediated Osteoclastogenesis and Increased Bone Mass Phenotype. J Cell Biochem 118:2231-2240
Singh, Pratibha; Hoggatt, Jonathan; Kamocka, Malgorzata M et al. (2017) Neuropeptide Y regulates a vascular gateway for hematopoietic stem and progenitor cells. J Clin Invest 127:4527-4540
Capitano, Maegan L; Broxmeyer, Hal E (2017) A role for intracellular and extracellular DEK in regulating hematopoiesis. Curr Opin Hematol 24:300-306
Clinkenbeard, Erica L; Hanudel, Mark R; Stayrook, Keith R et al. (2017) Erythropoietin stimulates murine and human fibroblast growth factor-23, revealing novel roles for bone and bone marrow. Haematologica 102:e427-e430
O'Leary, H A; Capitano, M; Cooper, S et al. (2017) DPP4 truncated GM-CSF and IL-3 manifest distinct receptor-binding and regulatory functions compared with their full-length forms. Leukemia 31:2468-2478
Lee, Man Ryul; Mantel, Charlie; Lee, Sang A et al. (2016) MiR-31/SDHA Axis Regulates Reprogramming Efficiency through Mitochondrial Metabolism. Stem Cell Reports 7:1-10
Broxmeyer, Hal E (2016) Enhancing the efficacy of engraftment of cord blood for hematopoietic cell transplantation. Transfus Apher Sci 54:364-72
Huang, X; Lee, M-R; Cooper, S et al. (2016) Activation of OCT4 enhances ex vivo expansion of human cord blood hematopoietic stem and progenitor cells by regulating HOXB4 expression. Leukemia 30:144-53

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