This COBRE has 6 objectives: 1) The development of a strong mentoring group of established investigators with complementary backgrounds in stem cell biology, molecular biology and transcriptional regulation of differentiation, pulmonary physiology and biology, and the translation of basic research to clinical therapy, 2) The enhancement of infrastructure support by providing core laboratories, administrative support and total resources to increase the research competitiveness of our faculty, 3) Recruit and retain funded young and established faculty so as to continue the establishment of RIH as a major stem cell research center. 4) Recruit underrepresented minority students, postdoctoral fellows and faculty through a Minority Mentor and Support Core, 5) Determine the true phenotype of marrow stem cells and its tissue fate. To study the transfer of phenotype information via microvesicles from injured tissue and to define mechanisms of transcriptional control of differentiation, 6) Translate basic stem cell studies into clinical trials on tissue restoration or correction in patients with chronic obstructive lung disease and refractory hematologic malignancies. An experienced group of scientists will mentor 3 promising young investigators and are prepared to mentor others in different research areas. The work is thematically coordinated around stem cell biology in general and approaches to modulating the stem cell phenoptype. The three projects are 1) Injured Lung and its Influence on Marrow Cell Phenotype, 2) Directed Stem Cell Hematopoieis and Differentiation and 3) Tyrosine Phosphatase Shp2 in Stem Cell Property Maintenance. These scientific projects are supported by the Administrative, Flow Cytometry, Molecular and Minority Mentor and Support Cores. Plans are outlined for the continued mentoring of junior P.l.s and specific approaches for evaluating the progress of the P.l.s and a plan to specifically guide the P.l.s to RO1 funding is included. Institutional commitment is strong. Plans are also outlined for the recruitment and development of new junior faculty. The award of this COBRE would effectively facilitate the continued development of a """"""""transplanted"""""""" Center for Stem Cell Biology. This grant holds real promise for expanding our understanding of stem cell biology and developing unique new approaches for tissue regeneration in lung and marrow diseases.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Exploratory Grants (P20)
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Special Emphasis Panel (ZRR1-RI-2 (01))
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Gorospe, Rafael
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Rhode Island Hospital
United States
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Aliotta, Jason M; Pereira, Mandy; Wen, Sicheng et al. (2017) Bone Marrow Endothelial Progenitor Cells Are the Cellular Mediators of Pulmonary Hypertension in the Murine Monocrotaline Injury Model. Stem Cells Transl Med 6:1595-1606
Wang, Lijun; Huang, Jiahui; Moore, Douglas C et al. (2017) SHP2 Regulates the Osteogenic Fate of Growth Plate Hypertrophic Chondrocytes. Sci Rep 7:12699
Wen, S; Dooner, M; Cheng, Y et al. (2016) Mesenchymal stromal cell-derived extracellular vesicles rescue radiation damage to murine marrow hematopoietic cells. Leukemia 30:2221-2231
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Quesenberry, Peter J; Goldberg, Laura R; Dooner, Mark S (2015) Concise reviews: A stem cell apostasy: a tale of four H words. Stem Cells 33:15-20
Mulvey, Hillary E; Chang, Audrey; Adler, Jason et al. (2015) Extracellular vesicle-mediated phenotype switching in malignant and non-malignant colon cells. BMC Cancer 15:571
Zhou, Yi; Mohan, Aron; Moore, Douglas C et al. (2015) SHP2 regulates osteoclastogenesis by promoting preosteoclast fusion. FASEB J 29:1635-45
Tang, Xiaoli; Zheng, Dong; Hu, Ping et al. (2014) Glycogen synthase kinase 3 beta inhibits microRNA-183-96-182 cluster via the ?-Catenin/TCF/LEF-1 pathway in gastric cancer cells. Nucleic Acids Res 42:2988-98
Quesenberry, Peter J; Goldberg, Laura; Aliotta, Jason et al. (2014) Marrow Hematopoietic Stem Cells Revisited: They Exist in a Continuum and are Not Defined by Standard Purification Approaches; Then There are the Microvesicles. Front Oncol 4:56
Mantripragada, Kalyan; Reagan, John L; Quesenberry, Peter J et al. (2014) Advances in cellular therapy for the treatment of leukemia. Discov Med 17:15-24

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