The effective genetic manipulation of pluripotent, reconstituting hematopoietic stem cells should lead to function correction of the mutant phenotype in inherited disorders of bone marrow-derived cells. The long term goal of our 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 stem cell behavior both in vitro and in vivo. The proposed Center membership draws from a group of well-funded investigators with diverse but complementary experience in hematopoiesis and stem cells biology, retroviral- and AV-mediated gene transfer, molecular genetics, virology, bone marrow transplantation and neonatology. The group is highly collaborative and interactive with NIH-funded projects that span basic, translational and clinical research. The cores proposed in this CCEMH submission are both more mature versions of the original cores supported by our previous Centers of Excellence in Molecular Hematology grant (Stem Cell Laboratory, Vector Production Facility and Mouse Core) and extensions of these 3 existing cores (Cell and Molecular Biology Core and Gene Therapy Working Group/Biostatistics Core) to further support hematology basic research, translational hematology trials utilizing stem cells and growth factors, and the development of gene transfer technology into translational trials. These two new cores are noteworthy, as they provide the infrastructure to rigorously perform human trials, while assessing quantitatively transgene expression and biochemical endpoints, a critical component in the evaluation of gene transfer protocols. Together the CCEMH represent a logical assembly of cores needed to continue the basic work in progress and to put in place support which we believe will be needed over the next 5 years.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Center Core Grants (P30)
Project #
5P30DK049218-08
Application #
6380949
Study Section
Special Emphasis Panel (ZDK1-GRB-6 (M1))
Program Officer
Badman, David G
Project Start
1999-09-15
Project End
2004-08-31
Budget Start
2001-09-01
Budget End
2002-08-31
Support Year
8
Fiscal Year
2001
Total Cost
$915,000
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Pediatrics
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Hoggatt, Jonathan; Singh, Pratibha; Tate, Tiffany A et al. (2018) Rapid Mobilization Reveals a Highly Engraftable Hematopoietic Stem Cell. Cell 172:191-204.e10
Xu, Linlin; Mohammad, Khalid S; Wu, Hao et al. (2016) Cell Adhesion Molecule CD166 Drives Malignant Progression and Osteolytic Disease in Multiple Myeloma. Cancer Res 76:6901-6910
Prasain, Nutan; Lee, Man Ryul; Vemula, Sasidhar et al. (2014) Differentiation of human pluripotent stem cells to cells similar to cord-blood endothelial colony-forming cells. Nat Biotechnol 32:1151-1157
Waning, David L; Li, Binghui; Jia, Nan et al. (2008) Cul4A is required for hematopoietic cell viability and its deficiency leads to apoptosis. Blood 112:320-9
Cai, Shanbao; Hartwell, Jennifer R; Cooper, Ryan J et al. (2006) In vivo effects of myeloablative alkylator therapy on survival and differentiation of MGMTP140K-transduced human G-CSF-mobilized peripheral blood cells. Mol Ther 13:1016-26
Li, Xiaxin; Le Beau, Michelle M; Ciccone, Samantha et al. (2005) Ex vivo culture of Fancc-/- stem/progenitor cells predisposes cells to undergo apoptosis, and surviving stem/progenitor cells display cytogenetic abnormalities and an increased risk of malignancy. Blood 105:3465-71
Srour, Edward F; Tong, Xia; Sung, Ki Woong et al. (2005) Modulation of in vitro proliferation kinetics and primitive hematopoietic potential of individual human CD34+CD38-/lo cells in G0. Blood 105:3109-16
Rinne, M L; He, Y; Pachkowski, B F et al. (2005) N-methylpurine DNA glycosylase overexpression increases alkylation sensitivity by rapidly removing non-toxic 7-methylguanine adducts. Nucleic Acids Res 33:2859-67
Tell, Gianluca; Damante, Giuseppe; Caldwell, David et al. (2005) The intracellular localization of APE1/Ref-1: more than a passive phenomenon? Antioxid Redox Signal 7:367-84
Bijangi-Vishehsaraei, Khadijeh; Saadatzadeh, M Reza; Werne, Adam et al. (2005) Enhanced TNF-alpha-induced apoptosis in Fanconi anemia type C-deficient cells is dependent on apoptosis signal-regulating kinase 1. Blood 106:4124-30

Showing the most recent 10 out of 42 publications