An understanding of unique properties of stem and progenitor cells is advancing rapidly. Initial successes in manipulating such cells for therapeutic advantages have intensified investigations (and enabled national centers that focus on embryonic stem cell plasticity, adult stem cell sources &potentials, and therapies for defined disorders). This revolution has opened new doors, but has also raised important new questions concerning key niche-specific regulators of progenitor cell growth, survival, and development. Our COBRE Program has been developed to address such questions. In Phase-I, we have: assembled a thematically focused team of talented investigators;engaged expert IAC, EAC and mentoring components;acquired several R01 and K01 awards;made major infrastructural advances (eg, new cores in cell separation, histopathology, bioinformatics and a new research building addition);and have extended intra-inter Institute interactions. Impacting scientific discoveries also have been made. In Phase-II, aims are to: #1] Support six exciting new research projects to advance mechanistic understandings of blood, vascular, neural, and skeletal muscle progenitor cell development in important disease and injury contexts;#2] Guide additional investigators to R01 funded status, recruit an additional senior scientist and at least two additional outstanding new junior investigators to bolster our Program;#3] Further develop key core facilities;#4] Continue to fortify infrastructure (new research wing, State biomedical bonds);and #5] Support new interactive seed projects towards synergistic co-investigator programs, and grant support. We will continue to investigate important niche-specific progenitor cell problems, and will focus on: BMP orthologue regulation of kidney response to injury and regeneration;R-spondin2 as a novel candidate regulator of skeletal muscle regeneration;Mechanisms of mural cell assisted de novo blood vessel formation from hES cells;DMA break repair in stem cells and affected microenvironments during lymphomagenesis;Slug as a key regulator of hematopoietic stem cell survival;and Jagged 1 maintenance of neural stem cell expansion and pluripotency. These projects share common scientific (and clinically relevant) themes;will foster state and national interactions;will advance the field (and funding) in significant ways;and will attract additional high caliber investigators to our Program. Overall efforts will forge a nationally competitive Center in this exciting discipline.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory Grants (P20)
Project #
8P20GM103465-10
Application #
8288119
Study Section
Special Emphasis Panel (ZRR1-RI-6 (01))
Program Officer
Gorospe, Rafael
Project Start
2003-09-30
Project End
2013-08-31
Budget Start
2012-06-01
Budget End
2013-08-31
Support Year
10
Fiscal Year
2012
Total Cost
$1,987,665
Indirect Cost
$666,957
Name
Maine Medical Center
Department
Type
DUNS #
071732663
City
Portland
State
ME
Country
United States
Zip Code
04102
He, Qing; Yang, Xuehui; Gong, Yan et al. (2014) Deficiency of Sef is associated with increased postnatal cortical bone mass by regulating Runx2 activity. J Bone Miner Res 29:1217-31
Han, Xiang Hua; Jin, Yong-Ri; Tan, Leonard et al. (2014) Regulation of the follistatin gene by RSPO-LGR4 signaling via activation of the WNT/*-catenin pathway in skeletal myogenesis. Mol Cell Biol 34:752-64
Ufkin, Melanie L; Peterson, Sarah; Yang, Xuehui et al. (2014) miR-125a regulates cell cycle, proliferation, and apoptosis by targeting the ErbB pathway in acute myeloid leukemia. Leuk Res 38:402-10
Bornstein, Sheila; Brown, Sue A; Le, Phuong T et al. (2014) FGF-21 and skeletal remodeling during and after lactation in C57BL/6J mice. Endocrinology 155:3516-26
Chen, Ying; Gridley, Thomas (2013) The SNAI1 and SNAI2 proteins occupy their own and each other's promoter during chondrogenesis. Biochem Biophys Res Commun 435:356-60
Yang, Xuehui; Gong, Yan; Tang, Yuefeng et al. (2013) Spry1 and Spry4 differentially regulate human aortic smooth muscle cell phenotype via Akt/FoxO/myocardin signaling. PLoS One 8:e58746
Boucher, Joshua M; Harrington, Anne; Rostama, Bahman et al. (2013) A receptor-specific function for Notch2 in mediating vascular smooth muscle cell growth arrest through cyclin-dependent kinase inhibitor 1B. Circ Res 113:975-85
Hoekstra, Elisa J; von Oerthel, Lars; van der Heide, Lars P et al. (2013) Lmx1a encodes a rostral set of mesodiencephalic dopaminergic neurons marked by the Wnt/B-catenin signaling activator R-spondin 2. PLoS One 8:e74049
Brown, Aaron C; Muthukrishnan, Sree Deepthi; Guay, Justin A et al. (2013) Role for compartmentalization in nephron progenitor differentiation. Proc Natl Acad Sci U S A 110:4640-5
Gong, Yan; Yang, Xuehui; He, Qing et al. (2013) Sprouty4 regulates endothelial cell migration via modulating integrin *3 stability through c-Src. Angiogenesis 16:861-75

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