Cartilage formation is driven by a developmental process known as chondrogenesis, which underlies growth and development of our joints and most bone. Failure in chondrogenesis leads to a variety of musculoskeletal diseases, including chondrodysplasias, osteoarthritis, heterotopic ossification, etc, affecting over 11 million Canadians and costing tens of billions in direct and indirect healthcare costs. Despite the increasing burden of musculoskeletal disease, there lacks effective therapeutics to alleviate these conditions, instead forcing us to rely on pain management, physiotherapy, or invasive joint replacement surgery.

The BMP signaling pathway is critically indispensable for chondrogenesis, and has emerged as a critical, druggable target for cartilage repair, with dozens of pre-clinical and clinical trials assessing the effectiveness of BMPs in joint and bone repair. Despite some preliminary success, too many gaps remain in our understanding of the molecular mechanisms underlying BMP signaling and chondrogenesis as a whole.

In close collaboration with Dr. Michael Underhill, this project aims to define the BMP-driven chondrogenic gene regulatory network, to identify potential novel therapeutic targets for treatment of chondrogenic diseases.

We model chondrogenesis using mice primary limb mesenchymal cells under differing levels of BMP activation, and employ a variety of techniques including Next Generation Sequencing at the School of Biomedical Engineering Sequencing Core (RNA-seq, ChIP-seq, CUT&Tag), bioinformatic tools, and immunohistochemistry.

We graciously acknowledge the Andrew Nord Fellowship in Rheumatology for funding this project.