Our Specific aims continue to explore the biology of stem cells.
Specific aim 1 uses simplified gradient separation to isolate stem cells. We plan studies which will isolate stem cells by functional characteristics. We believe that the most primitive quiescent stem cell may not express cell surface antigens attributable to long term engrafting cells. We have evidence that mul tipotential stem cells can proliferate and differentiate into cells of different germ layers. We plan additional clonal a nalysis to evaluate the engraftment capacity of pure stem cell populations. We will examine the nonhematopoieitc (epithelial) engraftment of our enriched populations of marrow derived stem cells. We plan to examine the factors which are known to regulate the proliferation and differentiation of mouse adult and embryonic stem cell populations. Finally, in specific aim 1, we will determine if stem cells isolated by gradient separation technology have the capacity to convert marrow cells into epithelial tissues in response to injury signals. In the second aim, importantly, we will attempt to distinguish between the presence of tissue specific stem cells and the existence of a pluripotent stem cell which resides in the bone marrow which, when stimulated by external injury signals, will respond by mobilization to the site of injury, convert into a new germ layer, and aid in repair of the injury. Relevance Bone marrow transplantation has been utilized for hematological failure or malignancy with increasing success. Recent animal models and a few clinical trials have used stem cell populations to repair injury via transplantation. We are attempting to define the cell types which can be used for such repair, develop simple and universal methods for isolating those cells and determining what factors in the microenvironment are responsible for stem cell self renewal and differentiation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA070970-13
Application #
8212936
Study Section
Special Emphasis Panel (ZCA1)
Project Start
2011-02-01
Project End
2013-01-31
Budget Start
2011-02-01
Budget End
2012-01-31
Support Year
13
Fiscal Year
2011
Total Cost
$302,974
Indirect Cost
Name
Johns Hopkins University
Department
Type
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Sharrow, Allison C; Perkins, Brandy; Collector, Michael I et al. (2016) Characterization of aldehyde dehydrogenase 1 high ovarian cancer cells: Towards targeted stem cell therapy. Gynecol Oncol 142:341-8
Gamper, Christopher J; Takemoto, Clifford M; Chen, Allen R et al. (2016) High-dose Cyclophosphamide is Effective Therapy for Pediatric Severe Aplastic Anemia. J Pediatr Hematol Oncol 38:627-635
Fox, Jennifer M; Moynihan, James R; Mott, Bryan T et al. (2016) Artemisinin-derived dimer ART-838 potently inhibited human acute leukemias, persisted in vivo, and synergized with antileukemic drugs. Oncotarget 7:7268-79
Kim, MinJung; Tan, Yee Sun; Cheng, Wen-Chih et al. (2015) MIR144 and MIR451 regulate human erythropoiesis via RAB14. Br J Haematol 168:583-97
Candia, Julián; Cherukuri, Srujana; Guo, Yin et al. (2015) Uncovering low-dimensional, miR-based signatures of acute myeloid and lymphoblastic leukemias with a machine-learning-driven network approach. Converg Sci Phys Oncol 1:
Brodsky, Robert A (2014) Paroxysmal nocturnal hemoglobinuria. Blood 124:2804-11
Rau, Rachel; Magoon, Daniel; Greenblatt, Sarah et al. (2014) NPMc+ cooperates with Flt3/ITD mutations to cause acute leukemia recapitulating human disease. Exp Hematol 42:101-13.e5
Tan, Yee Sun; Kim, MinJung; Kingsbury, Tami J et al. (2014) Regulation of RAB5C is important for the growth inhibitory effects of MiR-509 in human precursor-B acute lymphoblastic leukemia. PLoS One 9:e111777
Ma, Hayley S; Nguyen, Bao; Duffield, Amy S et al. (2014) FLT3 kinase inhibitor TTT-3002 overcomes both activating and drug resistance mutations in FLT3 in acute myeloid leukemia. Cancer Res 74:5206-17
Belet, Stefanie; Fieremans, Nathalie; Yuan, Xuan et al. (2014) Early frameshift mutation in PIGA identified in a large XLID family without neonatal lethality. Hum Mutat 35:350-5

Showing the most recent 10 out of 60 publications