Most of the bones of our body develop and grow by way of a cartilage template in a process called endochondral ossification. Cartilage has a single cell type, known as the chondrocyte, which secretes the abundant extracellular matrix in which these cells are embedded. The cartilage template of the skeleton deposited during development is transformed to bone in a highly organised developmental sequence that drives bone growth. Mutations in the genes encoding the cartilage ECM affect the way in which our long bones grow and result in a range of diseases classed as chondrodysplasias, the major feature of which is dwarfism. Chondrodysplasias are also often associated with early-onset osteoarthritis where the articular cartilage degrades causing joint failure and significant pain.
Our studies are focused on understanding how cartilage ECM proteins function, defining the mechanisms by which mutations in cartilage proteins cause chondrodysplasia, and understanding the mechanisms by which osteoarthritis develops. Defining precisely the mechanisms by which these diseases develop has the potential to highlight new opportunities for treatment which is the long-term goal of these studies.
Ray Boot-Handford is a Professor of Biochemistry within the Wellcome Trust Centre for Cell-Matrix Research. He is the Academic Lead for the Manchester BBSRC Doctoral Training Partnership. Ray chaired the British Society for Matrix Biology (2009-2015) and has served on the Arthritis Research UK Research Grant Subcommittee (1996-2000 & 2011-2015).
Ray obtained a Biochemistry degree from University College, Cardiff (1976) and PhD from University College London (1980). Ray moved to a postdoc with Mike Grant in Manchester to research basement membrane changes in diabetes. In 1985 Ray was awarded a Lions Club Fellowship to continue his work firstly at Rutgers Medical School, NJ, USA and more latterly at newly formed Jefferson Institute of Molecular Medicine in Philadelphia. In 1987, he returned to The University of Manchester on a RNIB Fellowship and was appointed to a lectureship in 1989. Ray’s lab was the first to clone mammalian collagen X sequences and went on to identify chondrodysplasias associated with mutations in collagen X. In 1999, Ray was awarded a Wellcome Trust Research Leave Fellowship to learn and apply mouse gene targeting techniques. The major current focus of the lab is in determining disease mechanisms associated with osteoarthritis and with mutations in cartilage genes such as type X collagen using in vivo mouse models of disease.