Abstract

Matrix Metalloproteinases and their natural inhibitors (TIMPs) regulate the dissolution of the extracellular matrix in growth and development, inflammatory and neoplastic diseases. The objective of this project is to investigate how cells orchestrate the episodic local dissolution of extracellular matrix by the orderly expression and function of MMPs and their inhibitors. Initially our studies are aimed at determining which MMPs are involved in the degradation of a single substrate (reconstituted fibrils of type I collagen) by a single cell type. To address this question we are employing a variety of molecular and cell biological approaches. Specifically we are pursuing mouse genetic approches (gene knock-out and replacement) in order to determine the function of various MMPs in extracellular matrix remodeling in health and disease.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Intramural Research (Z01)
Project #
1Z01DE000676-08
Application #
6814528
Study Section
(ODIR)
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2003
Total Cost
Indirect Cost

  Institution

Name
Dental & Craniofacial Research
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Szabova, Ludmila; Yamada, Susan S; Wimer, Helen et al. (2009) MT1-MMP and type II collagen specify skeletal stem cells and their bone and cartilage progeny. J Bone Miner Res 24:1905-16
Markovic, D S; Vinnakota, K; Chirasani, S et al. (2009) Gliomas induce and exploit microglial MT1-MMP expression for tumor expansion. Proc Natl Acad Sci U S A 106:12530-5
Tsutsui, T W; Riminucci, M; Holmbeck, Kenn et al. (2008) Development of craniofacial structures in transgenic mice with constitutively active PTH/PTHrP receptor. Bone 42:321-31
Ingvarsen, Signe; Madsen, Daniel H; Hillig, Thore et al. (2008) Dimerization of endogenous MT1-MMP is a regulatory step in the activation of the 72-kDa gelatinase MMP-2 on fibroblasts and fibrosarcoma cells. Biol Chem 389:943-53
Szabova, L; Chrysovergis, K; Yamada, S S et al. (2008) MT1-MMP is required for efficient tumor dissemination in experimental metastatic disease. Oncogene 27:3274-81
Shi, Joanne; Son, Mi-Young; Yamada, Susan et al. (2008) Membrane-type MMPs enable extracellular matrix permissiveness and mesenchymal cell proliferation during embryogenesis. Dev Biol 313:196-209
Michienzi, Stefano; Cherman, Natasha; Holmbeck, Kenn et al. (2007) GNAS transcripts in skeletal progenitors: evidence for random asymmetric allelic expression of Gs alpha. Hum Mol Genet 16:1921-30
Atkinson, Jeffrey J; Toennies, Holly M; Holmbeck, Kenn et al. (2007) Membrane type 1 matrix metalloproteinase is necessary for distal airway epithelial repair and keratinocyte growth factor receptor expression after acute injury. Am J Physiol Lung Cell Mol Physiol 293:L600-10
Madsen, Daniel H; Engelholm, Lars H; Ingvarsen, Signe et al. (2007) Extracellular collagenases and the endocytic receptor, urokinase plasminogen activator receptor-associated protein/Endo180, cooperate in fibroblast-mediated collagen degradation. J Biol Chem 282:27037-45
Basile, John R; Holmbeck, Kenn; Bugge, Thomas H et al. (2007) MT1-MMP controls tumor-induced angiogenesis through the release of semaphorin 4D. J Biol Chem 282:6899-905

Showing the most recent 10 out of 40 publications