Angiogenesis is the formation of new blood vessels from existing structures and is involved in the regulation of wound repair and the pathobiology of numerous disease states including solid tumor growth. Because angiogenesis is regulated by a complex interaction of receptor mediated signals modified by the activities of growth factors, cytokines, proteinases, lipid and components of the extracellular matrix, it sis important for institutions with a focus on angiogenesis to include experimental programs in these and other areas such as mechanisms and intracellular traffick. As a result, this application requests support from the IDeA Program to establish a COBRE in Angiogenesis and involves the collaborative interests of a group of four new (non-R01 funded) and two established investigators at the newly formed (1998) Center for Molecular Medicine at the Maine Medical Center. The theme focuses on Signaling Paradigms in Angiogenesis as a result of the long term research interests of the Program's PI in the biology of the endothelial cell at the cellular and molecular level and the institutional commitment to support a program in Angiogenesis. The motives for this application include the use of this award to (i) support promising young independent investigators in this field, (ii) expand existing institution resources to create a larger critical mass of mechanism-oriented junior and senior investigators in this area, investigator needs and (iv) provide resources requisite for the establishment of an internationally recognized non-profit research institution in the broad area of mechanistic Vascular Biology. The application is comprised of five projects which were chosen in the field of angiogenesis and the areas of interest include the mechanisms of (i) cooperativity between FGF and Jagged 1 signaling in the regulation of chord formation and in the regulation of a stable collateral circulatory system following ischemic heart damage, (ii) the antagonism of FGFR signaling and the regulation of branching by Sprouty, (iii) inflammatory- mediated release of FGF2 as a covalent complex with plasminogen fragments in vivo, (iv) the TGFbeta-receptor-associated protein, endoglin, to mediate arteriovenous malformations and (v) Twist as a transcriptional mediator of tubulogenesis. Program expansion by 2001 will include the recruitment of six investigators with genetic, cellular, and molecular signaling expertise mediated by (i) proteinases and their inhibitors, (ii) extracellular matrix, (iii) cadherins, (iv) VEGF in lymphogenesis and angiogenesis, (v) G-protein-coupled receptors and (vi) intracellular trafficking but the resources from this award will only be used for Program expansion in areas (i) and (ii). It is anticipated that this award will not only enable the Ctr. for Mol. Med. to achieve its goal at a more rapid and efficient rate but the insight derived from these investigators may significantly impact the fields of Angiogenesis and Vascular Biology.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Exploratory Grants (P20)
Project #
5P20RR015555-02
Application #
6394811
Study Section
Special Emphasis Panel (ZRR1-RCMI-2 (01))
Program Officer
Mccullough, Willie
Project Start
2000-09-15
Project End
2005-08-31
Budget Start
2001-09-01
Budget End
2002-08-31
Support Year
2
Fiscal Year
2001
Total Cost
$2,155,400
Indirect Cost
Name
Maine Medical Center
Department
Type
DUNS #
City
Portland
State
ME
Country
United States
Zip Code
04102
Soley, Luna; Falank, Carolyne; Reagan, Michaela R (2017) MicroRNA Transfer Between Bone Marrow Adipose and Multiple Myeloma Cells. Curr Osteoporos Rep 15:162-170
Young, K; Krebs, L T; Tweedie, E et al. (2016) Endoglin is required in Pax3-derived cells for embryonic blood vessel formation. Dev Biol 409:95-105
Ames, Jacquelyn J; Contois, Liangru; Caron, Jennifer M et al. (2016) Identification of an Endogenously Generated Cryptic Collagen Epitope (XL313) That May Selectively Regulate Angiogenesis by an Integrin Yes-associated Protein (YAP) Mechano-transduction Pathway. J Biol Chem 291:2731-50
Contois, Liangru W; Akalu, Abebe; Caron, Jennifer M et al. (2015) Inhibition of tumor-associated ?v?3 integrin regulates the angiogenic switch by enhancing expression of IGFBP-4 leading to reduced melanoma growth and angiogenesis in vivo. Angiogenesis 18:31-46
Motyl, Katherine J; Bishop, Kathleen A; DeMambro, Victoria E et al. (2013) Altered thermogenesis and impaired bone remodeling in Misty mice. J Bone Miner Res 28:1885-97
Bai, Hao; Chen, Kang; Gao, Yong-Xing et al. (2012) Bcl-xL enhances single-cell survival and expansion of human embryonic stem cells without affecting self-renewal. Stem Cell Res 8:26-37
Stohn, J Patrizia; Perreault, Nicole G; Wang, Qiaozeng et al. (2012) Cthrc1, a novel circulating hormone regulating metabolism. PLoS One 7:e47142
Kirov, Aleksandr; Al-Hashimi, Huda; Solomon, Phil et al. (2012) Phosphatidylserine externalization and membrane blebbing are involved in the nonclassical export of FGF1. J Cell Biochem 113:956-66
Apra, Caroline; Richard, Laurence; Coulpier, Fanny et al. (2012) Cthrc1 is a negative regulator of myelination in Schwann cells. Glia 60:393-403
Contois, Liangru W; Nugent, Desiree P; Caron, Jennifer M et al. (2012) Insulin-like growth factor binding protein-4 differentially inhibits growth factor-induced angiogenesis. J Biol Chem 287:1779-89

Showing the most recent 10 out of 101 publications