Research
We are interested in the molecular structure
and function of the extracellular matrix of bone, cartilage and other
tissues that form the mammalian skeleton.
Our focus is on protein assembly. We are studying mechanisms of
collagen polymerization, covalent cross-linking through the lysyl
oxidase mechanism, interactions between different types of collagens to
form hybrid fibrils and proteolytic pathways of matrix turnover and
degradation. One broad aim is to understand how articular cartilage is
destroyed in osteoarthritis, a common debilitating disease.
The
consequences of mutations that cause rare heritable disorders of the
skeleton are also being examined at the protein level to understand the
link from gene defect to tissue and clinical phenotype. A range of
methods in protein analysis is being applied, including ion-trap mass
spectrometry, to determine unique post-translational features and other
properties of functional domains. Chondrocyte cell lines provide an
experimental system for examining the assembly of macromolecules into
extracellular matrix.
Selected
Publications
Eyre DR, Wu J-J, Fernandes RJ, Pietka TA, Weis MA. (2002) Recent
developments in cartilage research: Matrix biology of the collagen
II/IX/XI heterofibril network. Biochem. Soc. Trans. 30(6), 894-899
Matsui
Y, Chansky HA, Barahmand-Pour F, Zielinska-Kwiatkowska A, Tsumaki N,
Myoui A, Yoshikawa H, Yang L, Eyre DR. (2003) COL11A2 collagen gene
transcription is differentially regulated by EWS / ERG sarcoma fusion
protein and wild-type ERG. J. Biol. Chem. 278(13), 11369-11375
Matsui
Y, Wu J, Weis MA, Pietka T, Eyre D. (2003) Matrix deposition of
tryptophan-containing allelic variants of type IX collagen in
developing human cartilage. Matrix Biol. 22(2), 122-128
Wu
JJ, Eyre DR. (2003) Intervertebral disc collagen: Usage of the short
form of ?1(IX) in bovine nucleus pulposus. J. Biol. Chem. 278(27),
24521-24525
Fernandes
RJ, Schmid TM, Eyre DR. (2003) Assembly of collagen types II, IX and XI
into nascent heterofibrils by a rat chondrocyte cell line. Eur. J.
Biochem. 270(15), 3243-3250
Matsui
Y, Mirza SK, Wu J-J, Carter B, Belgrouparba C, Shaffrey CI, Chapman JR,
Eyre DR. (2004) The Association of lumbar spondylolisthesis with
collagen IX tryptophan alleles. J. Bone Joint Surg.