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Matthew P. Vincenti, Ph.D.
Title(s):
Research Associate Professor of Medicine
Department(s):
Medicine
Education:
University of Vermont, Burlington, VT/ BA/ Biology/1984
SUNY Upstate Medical Center/PhD/Micro.Immuno./1991
Programs:
Program in Experimental and Molecular Medicine
Contact Information:
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VA Medical Center, Mail Code 151 215 North Main Street White River Junction VT 05001 |
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Phone: 802-295-9363 X6403 Fax: 802-296-6308 Email: mpv@dartmouth.edu |
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Selected Publications: |
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Elliott SF, Coon CI, Hays E, Stadheim TA, Vincenti MP. Bcl-3 is an interleukin-1-responsive gene in chondrocytes and synovial fibroblasts that activates transcription of the matrix metalloproteinase 1 gene. Arthritis Rheum. 2002 Dec;46(12):3230-9. (view details on MedLine) Elliott S, Hays E, Mayor M, Sporn M, Vincenti M. The triterpenoid CDDO inhibits expression of matrix metalloproteinase-1, matrix metalloproteinase-13 and Bcl-3 in primary human chondrocytes. Arthritis Res Ther. 2003;5(5):R285-91. Epub 2003 Jul 8. (view details on MedLine) Raymond L, Eck S, Mollmark J, Hays E, Tomek I, Kantor S, Elliott S, Vincenti M. Interleukin-1 beta induction of matrix metalloproteinase-1 transcription in chondrocytes requires ERK-dependent activation of CCAAT enhancer-binding protein-beta. J Cell Physiol. 2006 Jun;207(3):683-8. (view details on MedLine) Fava RA, Elliott S, Raymond L, Mollmark J, Hays E, Honda T, Gribble GW, Sporn MB, Vincenti MP. The synthetic triterpenoid TP-222 inhibits RANKL stimulation of osteoclastogenesis and matrix metalloproteinase-9 expression. J Rheumatol. 2007 May;34(5):1058-68. Epub 2007 Mar 15. (view details on MedLine) Vincenti MP, Brinckerhoff CE. Signal transduction and cell-type specific regulation of matrix metalloproteinase gene expression: can MMPs be good for you? J Cell Physiol. 2007 Nov;213(2):355-64. Review. (view details on MedLine) Cortez DM, Feldman MD, Mummidi S, Valente AJ, Steffensen B, Vincenti M, Barnes JL, Chandrasekar B. IL-17 stimulates MMP-1 expression in primary human cardiac fibroblasts via p38 MAPK- and ERK1/2-dependent C/EBP-beta , NF-kappaB, and AP-1 activation. Am J Physiol Heart Circ Physiol. 2007 Dec;293(6):H3356-65. Epub 2007 Oct 5. (view details on MedLine) |
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Professional Interests:
The Matrix Metalloproteinases (MMP) are zinc and calcium-dependent endopeptidases that control the deposition of a wide range of matrix proteins during normal development and wound healing. MMP expression is elevated in response to inflammatory signals and this contributes to abnormal matrix remodeling in cancer, arthritis and cardiovascular disease.
Research in Dr. Vincenti’s laboratory focuses on inflammatory signal transduction that leads to MMP transcription in mesenchymal, epithelial and myeloid cells. These studies have established that IL-1 activation of the nuclear factor-kappa B (NF-κB) and the extracellular signal regulated kinase (ERK) pathways are critical processes for transcriptional activation of collagenase-1/MMP-1. Recent data demonstrate that RelA and Bcl-3 are two NF-κB family members that are absolutely required for gene activation. Additional work has established that IL-1 activation of the ERK pathway leads to phosphorylation of the transcription factor C/EBPβ, which directly binds to the MMP-1 promoter and facilitates transcription.
The laboratory is also investigating the mechanisms of MMP repression by a group of synthetic compounds known as triterpenoids (TP). These compounds target many of the same pathways that are activated by inflammatory mediators, and can effectively inhibit Collagenase-1/MMP-1, GelatinaseB/MMP-9 and Collagenase-3/MMP-13 gene activation. An exciting new finding is that TP can inhibit MMP-9 expression and osteoclast formation by RANKL. Given the central role of osteoclasts in diseases such as rheumatoid arthritis and metastatic bone disease, this research has important clinical implications for the development of novel therapies.
Courses Taught:
Protein Kinase Cascades and Nuclear Factor Kappa B Pathway; Signaling Core Course, Pharmacology&Toxicology, DMS.
Connective Tissue Biology; Rheumatology Fellows Core Conference; DHMC
Grant Information:
VA Merit Review Award (Vincenti, Matthew) 10/1/2007 to 9/30/2011 “Regulation of Matrix Metalloproteinase-1 by the NF-kB and ERK Pathways”
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