Objective Following skeletal muscle injury, resident fibroblasts proliferate and release cytokines that enhance muscle regeneration. Fibroblasts also secrete chemokines to recruit cellular migration, and extracellular proteins that stabilize the site of injury. However, in chronic diseases, such as Duchenne Muscular Dystrophy (DMD), continual muscle damage shifts fibroblasts towards an uncontrolled fibrotic and inflammatory phenotype. Excessive fibrosis and inflammation are prominent pathological features of DMD and inhibit muscle function and repair by replacing the tissue with fibrotic scars, adipose tissue, and necrosis. The fundamental question my proposal will address is why fibroblasts shift from regenerative-favouring cells in healthy muscle, but lead to fibrotic accumulation in dystrophic muscle. My proposal will use a novel approach to investigate specific fibroblast populations. Whether all fibroblasts are capable of promoting both fibrosis and muscle regeneration, or if there are fibroblast subpopulations that produce factors leading to one or the other outcome, is not currently known. The heterogeneity of fibroblast populations within skeletal muscle remains to be determined. By using lineage tracing and flow cytometry to map cell fate during the progression of muscle degeneration in a mouse model of DMD, my project will identify aberrant changes in fibroblast populations and elucidate how these cells interact with inflammatory cells and satellite cells. Finally, I will extract dystrophic fibroblasts and transplant them into non-dystrophic mouse muscle to determine whether fibroblasts populations can reprogram, or shift, towards a regenerative-favouring cell fate which could lead to a new tailored field of personalized medicines. These provocative studies will be integrated with ongoing research in Dr Morgan’s laboratory aimed at developing new therapeutics regimens for DMD. Fields of science medical and health sciencesbasic medicineneurologymuscular dystrophiesduchenne muscular dystrophy Keywords Muscular Dystrophy Fibrosis Transplantation Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Call for proposal H2020-MSCA-IF-2014 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator UNIVERSITY COLLEGE LONDON Net EU contribution € 183 454,80 Address GOWER STREET WC1E 6BT London United Kingdom See on map Region London Inner London — West Camden and City of London Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 183 454,80