Bone Biology Lab

Cancer in bone and cancer dormancy

Cancer cell dormancy is the phenomenon in which cancer cells lodge themselves in bone tissue and then become dormant (sleeping) for months or years, before ‘waking’ to form actively growing cancers. We are developing a detailed cellular and molecular understanding of cancer cell dormancy in bone, to support our mission. We predominantly focus on the blood cancer multiple myeloma, which grows in bone, and on breast and prostate cancer, both of which commonly spread to bone.

Our work in cancer dormancy is underpinned by state-of-the-art imaging technology, including two-photon intravital imaging, and by single-cell transcriptomic analysis of cancer cells residing in bony niches.

Cancer-associated bone disease

When cancers grow in the skeleton, they can lead to bone disease that is painful, debilitating and significantly worsens a patient’s prognosis. Our lab has developed animal models of myeloma bone disease. Using these, we have identified the critical molecular pathways that tumour cells hijack to increase bone resorption (RANKL pathway) and inhibit bone formation (Wnt and Activin), causing bone disease. This has allowed us to identify targets and develop agents that inhibit bone resorption (anti-RANKL, ZOL) and stimulate bone formation (ActRIIA.Fc, anti-Dkk1, anti-sclerostin), and to translate these findings into treatments.

Genetics of bone disease

We are working with international collaborators to identify the genetic causes and molecular mechanisms underlying the onset and progression of osteoporosis, and other bone and cartilage diseases. Our achievements include identifying more than 500 sites across the human genome that determine bone mineral density, as well as numerous potential targets for future drug development in osteoporosis and other bone diseases.