About our research

Connective tissues are dynamic systems, which are continually undergoing change throughout development and adult life. Connective tissue homeostasis (the biosynthesis, deposition, degradation and turnover of extracellular matrix (ECM) molecules) is controlled primarily by the major resident cell type and their response to stimuli such as specific cytokines, growth factors and surface receptors. The turnover of ECM is regulated by proteolytic enzymes including metzencin family of enzymes, as well as others.  We are using transgenic approaches to investigate the disregulation of ECM synthesis and breakdown that leads to two opposing pathology aspects of connective tissue.

 

1. Fibrosis

In fibrosis the repair process that includes synthesis and deposition of new components is impaired for unknown reasons. Accompanying these events is a fundamental genetic reprogramming of the resident cell, the fibroblast, resulting in differential expression of matrix-modulating enzymes such as metalloproteinases (MMPs) and their inhibitors (TIMPs). We are investigating the effect of genes that influence that balance in gain and loss of function experiments to readdress the balance.

 

2. Osteoarthritis

Osteoarthritis (OA), the commonest form of joint disease, is characterised by the progressive destruction of articular cartilage matrix. We are taking a broad view at the whole synovial joints from synovium, ligaments, bone and articular cartilage to investigate what goes wrong in OA and ways to ameliorate the disease.

 

We are situated in the Institute of Ageing and Chronic Disease

William Henry Duncan Building

6 West Derby Street

Liverpool

L7 8TX

United Kingdom

  

  • We have vast experience of generating transgenic mice for gain and loss of function.
  • We have recently adopted CRISPR for genetic modification.
  • We have used in vivo imaging to trace cell-specific populations in musculoskeletal environments.
  • We have a number of inducible Cre recombinase mice that can target fibroblasts, chondrocytes and osteoblasts