Graduate Student Hong Kong University of Science and Technology Hong Kong University of Science and Technology, Hong Kong
Abstract: Blood-based biomarkers are gaining prominence in clinical research for disease prognosis, diagnosis, and monitoring of disease progression. Sarcopenia and muscular dystrophies are diseases that result in the loss of muscle mass and functional decline, leading to frequent falls and reduced mobility. Currently, there are no definitive sets of biomarkers for muscle-related diseases. This project aims to identify blood-based biomarkers to stage muscle disease progression and muscle regeneration. We profiled the blood proteome across different timepoints following injury and regeneration using an induced hindlimb muscle injury mouse model. In addition to observing the upregulation of DNA damage and repair mechanisms at 1dpi (day post-injury), muscle-associated proteins were upregulated, correlating to muscle structure development and myogenesis. Also, proteins correlated to oxidative phosphorylation are enriched at 1 and 3 dpi, whereas proteins associated with neurogenesis and epithelial-mesenchymal transition are enriched at 5 and 7 dpi. We will then focus on determining the origin of these circulating proteins, identifying the role of adult muscle stem cells (MuSCs) and fibro-adipogenic progenitors (FAPs) in secreting signaling factors into the bloodstream and facilitating the muscle repair process. Finally, we strive to verify those biomarkers during physiological and pathological conditions by profiling the muscle strength and blood proteome in physiologically aged and dystrophic mice. Using a blood proteomics approach to stage muscle pathologies, we can investigate the functional status of MuSCs and FAPs in aging and diseased mice, allowing for the non-invasive assessment of disease progression and the regenerative capacity of skeletal muscle.
Funding Source: Work was supported by the Hong Kong Research Grant Council (GRF16100322, GRF16102021, GRF16101524), the University Grants Committee, the Croucher Foundation, and the Hong Kong Center for Neurodegenerative Diseases, InnoHK,HKSAR.
