Bone Biology Lab
Cancer in bone and cancer dormancy: A key research goal of the lab is to understand how tumours grow in the skeleton and to devise new ways to eliminate cancers in bone. To do this, we are developing a detailed cellular and molecular understanding of cancer cell dormancy in bone. This is the phenomenon in which cancer cells lodge in bone then become dormant (or sleeping) for months or years, before ‘waking’ to form actively growing cancers. We focus particularly 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 and the bony niche in which they reside.
Read more: Researchers reveal key to targeting dormant cancer cells
Read more: How to wake a sleeping cancer cell
Cancer-associated bone disease: When cancers grow in the skeleton, they can lead to devastating bone disease that is painful, debilitating and sharply worsens prognosis. We have developed animal models of myeloma bone disease, and used them to identify 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 led 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 into treatments.
Genetics of bone disease: With international collaborators, we are working to identify genetic causes and molecular mechanisms underlying the onset and progression of osteoporosis and other bone and cartilage disease. Among other advances, this work has recently identified over 500 sites across the human genome that determine bone mineral density, identifying numerous potential targets for future drug development in osteoporosis and other bone diseases.