Abstract

The purpose of this project is to characterize the role of GRO-a, an a-chemokine recently demonstrated by Dr. Miller's laboratory to be a major environmental factor that modulates the response of oligodendrocyte precursors to PDGF. In the first Specific Aim, the chemokine structural motifs required to enhance the PDGF proliferation response of oligodendrocyte precursors will be defined. In the second Specific Aim, the applicant intends to establish optimal conditions for interactions between GRO-alpha and PDGF to elicit oligodendrocyte precursor chemotaxis, and the capacity of GRO-alpha to enhance PDGF receptor signaling. In the third Specific Aim, molecular mechanisms of GRO-alpha action will be elucidated by evaluating ligand binding characteristics, as well as by determining the involvement of calcium and G proteins in signal transduction cascade. In the fourth Specific Aim, the distribution of biologically effective chemokines in the developing spinal cord will be determined.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS036674-04
Application #
6187875
Study Section
Special Emphasis Panel (ZRG1-NEUC (01))
Program Officer
Behar, Toby
Project Start
1997-08-01
Project End
2001-05-31
Budget Start
2000-06-01
Budget End
2001-05-31
Support Year
4
Fiscal Year
2000
Total Cost
$201,233
Indirect Cost

  Institution

Name
Case Western Reserve University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106

  Publications

Liu, LiPing; Belkadi, Abdelmadjid; Darnall, Lindsey et al. (2010) CXCR2-positive neutrophils are essential for cuprizone-induced demyelination: relevance to multiple sclerosis. Nat Neurosci 13:319-26
Tsai, Hui-Hsin; Macklin, Wendy B; Miller, Robert H (2009) Distinct modes of migration position oligodendrocyte precursors for localized cell division in the developing spinal cord. J Neurosci Res 87:3320-30
Caprariello, A V; Miller, R H; Selkirk, S M (2009) Foamy virus as a gene transfer vector to the central nervous system. Gene Ther 16:448-52
Kerstetter, A E; Padovani-Claudio, D A; Bai, L et al. (2009) Inhibition of CXCR2 signaling promotes recovery in models of multiple sclerosis. Exp Neurol 220:44-56
Bai, Lianhua; Lennon, Donald P; Eaton, Valerie et al. (2009) Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis. Glia 57:1192-203
Liu, Jinbo; Lin, Feng; Strainic, Michael G et al. (2008) IFN-gamma and IL-17 production in experimental autoimmune encephalomyelitis depends on local APC-T cell complement production. J Immunol 180:5882-9
Selkirk, Stephen M; Morrow, Jay; Barone, Tara A et al. (2008) Elevation of osteopontin levels in brain tumor cells reduces burden and promotes survival through the inhibition of cell dispersal. J Neurooncol 86:285-96
Miller, Robert H; Mi, Sha (2007) Dissecting demyelination. Nat Neurosci 10:1351-4
Miller, Robert H; Bai, Lianhua (2007) Cellular approaches for stimulating CNS remyelination. Regen Med 2:817-29
Fuller, Molly L; DeChant, Anne K; Rothstein, Brian et al. (2007) Bone morphogenetic proteins promote gliosis in demyelinating spinal cord lesions. Ann Neurol 62:288-300

Showing the most recent 10 out of 25 publications