Clinical PhD Programme at the University of Cambridge: 'Defining the origin and fate of Fibroblast Activation Protein (FAP) expressing cells in health and disease'. (360G-Wellcome-094793_Z_10_Z)

A population of tumour stromal cells, identified by Fibroblast Activation Protein (FAP) expression, are essential for suppressing the immune response directed toward the tumour. FAP+ cells are present in inflamed tissues, in healing wounds, during embryological development and recent work from our laboratory has found them in a wide range of normal adult tissue, including muscle, bone marrow and the kidney. Depleting FAP+ cells in mice leads to significant weight loss and skeletal muscle loss. Clearly FAP+ cells have a fundamental role in both health and disease. Their function in different tissues is not clearly defined but raises the question of whether they are all related. Are all FAP+ cells derived from a common lineage? Understanding the origins and fates of these cells will have significant implications for developing effective cancer therapies but may also provide evidence of a cell linking inflammation, healing and tissue specific regeneration. Key goals 1. Generate a BAC Transgenic (Tg) mouse in which FAP+ cells, and all their progeny, can be conditionally marked to express yellow fluorescent protein in vivo. 2. Use the Tg mouse to determine whether FAP+ cells in the tissues are derived from a common embryonic precursor and whether FAP+ cells can become FAP- in vivo. 3. Define the origins of FAP+ cells in acutely and chronically inflamed tissues.