Matthew P. Vincenti, Ph.D.
Associate Professor of Medicine
University of Vermont, Burlington, VT/ BA/ Biology/1984
SUNY Upstate Medical Center/PhD/Micro.Immuno./1991
Program in Experimental and Molecular Medicine
VA Medical Center, Mail Code 151
215 North Main Street
White River Junction VT 05001
Phone: 802-295-9363 X6403
The central focus of my research is to define how inflammation regulates matrix metalloproteinase (MMP) gene expression in arthritis and cancer. The MMPs are zinc- and calcium-dependent endopeptidases that remodel of a wide range of matrix proteins during normal development and wound healing. The inflammatory cytokine interleukin-1beta (IL-1B) drives MMP expression in connective tissue cells, leading to connective tissue destruction in arthritis. Similarly, IL-1B activates MMP expression by cancer cells, promoting a more invasive phenotype in tumors. Recent work in my laboratory has demonstrated that IL-1B stimulates MMP gene transcription through specific transcription factors such as nuclear factor-kappa B (NF-kB) and CCAAT/enhancer-binding protein beta (CEBPB). These and other transcription factors are recruited to defined regulatory elements in MMP promoter regions through IL-1B-dependent activation of specific cellular kinases. The long-term goal of this research is to identify pathway-specific targets in connective tissue cells and tumors that will help develop novel therapies for arthritis and cancer.
Rotations and Thesis Projects:
Characterization of the roles of interleukin-1beta and matrix metalloproteinases during tumor cell invasion.
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
Protein Kinase Cascades and Nuclear Factor Kappa B Pathway; Signaling Core Course, Pharmacology&Toxicology, DMS.
Connective Tissue Biology; Rheumatology Fellows Core Conference; DHMC
I received my Ph.D. in Microbiology and Immunology from SUNY Upstate Medical Center in 1992 and performed my postdoctoral work at Dartmouth. I joined the Dartmouth faculty in 1997 and established my current laboratory at the VA Medical Center in 2003.
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)
Armstrong DA, Phelps LN, Vincenti MP. CCAAT enhancer binding protein-beta regulates matrix metalloproteinase-1 expression in interleukin-1beta-stimulated A549 lung carcinoma cells. Mol Cancer Res. 2009 Sep;7(9):1517-24. Epub 2009 Sep 1. (view details on MedLine)
Petrella BL, Armstrong DA, Vincenti MP. CCAAT-enhancer-binding protein beta activation of MMP-1 gene expression in SW1353 cells: independent roles of extracellular signal-regulated and p90/ribosomal S6 kinases. J Cell Physiol. 2011 Dec;226(12):3349-54. doi: 10.1002/jcp.22693. (view details on MedLine)
Petrella BL, Armstrong DA, Vincenti MP. Interleukin-1 beta and transforming growth factor-beta 3 cooperate to activate matrix metalloproteinase expression and invasiveness in A549 lung adenocarcinoma cells. Cancer Lett. 2012 Jul 13 (view details on MedLine)
Petrella, BL, Armstrong, DA, Vincenti, MP. Interleukin-1 Beta and transforming growth factor-Beta 3 cooperate to activate matrix metalloproteinase expression and invasiveness in A549 aung adenocarcinoma cells. Cancer Letters. In press. 2012.