Project description:The study explores how maximal-intensity contractions and rapamycin impact the proteome and phosphoproteome of mouse skeletal muscle.
Project description:Cancer is considered as a disease of a specific organ, but its effects are felt throughout the body. The systemic effects of cancer can lead to weakness in muscles and heart, which hastens cancer-associated death. The majority of preclinical studies, including our own, on cancer-induced skeletal muscle defects utilized mouse models and C2C12 myoblast cell line of mouse origin (>7,700 publications). However, a recent study reported distinct metabolic pathways in mouse compared to human. For example, while higher fasting circulating levels of glucose in human is associated with shortened lifespan, it is associated with longer lifespan in mouse. Since the metabolic activity of the skeletal muscle primarily determines circulating glucose levels, skeletal muscle in mouse and human may function differently and not all skeletal muscle defects noted in tumor-bearing mice may not translate into human. Therefore, we developed a robust human model system using human muscle stem cells to understand cancer-induced skeletal muscle defects in human. We found conditioned media from breast cancer cell lines affected cell molecular biomarkers (e.g. PAX7 annd MyOD) and cell surface markers (e.g. CD82, CD54 and CD90) which were associated with dynamic changes of mRNAs, proteins and peptides in human muscle stem cells or human myotubes differentiated from human muscle stem cells. This study will help in cost-effective discovery of drugs that are effective irrespective genetic ancestry and reveal utility of two class of drugs to overcome cancer-induced skeletal muscle defects
Project description:This study aimed to investigate the effects of glucose restriction (GR) on energy metabolism and muscle fiber type in skeletal muscle. To achieve this goal, we created a mouse model of innate glucose limitation by mutating the major glucose transporter 4 (Glut4) in skeletal muscle. We performed proteomic and phosphoproteomic analyzes of gastrocnemius samples from 12-week-old male Glut4m mice, with or without low-intensity treadmill training.
Project description:To identify BVES-interacting proteins from mouse skeletal muscle, we performed IP-mass from AAV9-BVES-HA injected mouse skeletal muscle using the anti-HA magnetic beads.
Project description:This study aimed to investigate the effect of glucose restriction (GR) on energy metabolism and muscle fibre type in skeletal muscle. To achieve this goal, we constructed a mouse model of innate glucose restriction by mutating the glucose transporter 4 (Glut4), the major glucose transporter in skeletal muscle. We performed proteomic and phosphoproteomic analysis on gastrocnemius samples of male Glut4m mice at 12-week age, with or without a 4-week low-intensity training.
Project description:The epigenomic regulation is a part of Gene Regulatory Network (GRN). During we study the reprogramming of GRN adaptive to atrophic stimulation in skeletal muscle, we performed Histone 3 lysine 27 (H3K27) acetylation (H3K27ac) ChIP-seq assay using mouse skeletal muscle with or without denervation. This dataset combining with our snATAC datasets enable us to infer the candidate enhancer that could regulate muscle protein metabolism and energy metabolism during atrophy.
Project description:Investigation of age-dependent changes in the proteomic profile of Dysferlin-deficient mouse skeletal muscle relative to healthy muscle.
