Projects Debrief
Skeletal muscle exhibits remarkable structural and functional heterogeneity, demonstrating a high degree of plasticity that allows it to adapt to physiological and pathological conditions, including exercise training, disuse, aging, muscular dystrophy, chronic disease, and pharmacological interventions. This plasticity is crucial for maintaining physical performance and responding to metabolic challenges such as changes in energy and amino acid availability during starvation or chronic disease states. My research program focuses on two fundamental aspects of skeletal muscle physiology: glucose homeostasis and muscle performance, under both normal and diseased conditions. My lab explores these themes through three interconnected research projects:
1. Role of Metabolic Signaling in the Maintenance of Skeletal Muscle and Neuromuscular Junction (NMJ) Plasticity: The AKT signaling pathway in skeletal muscle is a critical regulator of glucose homeostasis, growth, and function. While skeletal muscle-specific AKT is dispensable for glucose uptake, it is indispensable for muscle mass maintenance and performance. Preliminary findings from my lab suggest that insulin signaling via AKT in skeletal muscle regulates NMJ structural stability, a key determinant of motor function. Given the NMJ’s role as the primary communication site between motor neurons and muscle fibers, its integrity is essential for maintaining contractile function. This project employs RNA in situ hybridization to track Acetylcholine Receptor (AChR) turnover, providing insights into NMJ remodeling dynamics. Additionally, we are implementing a gene therapy approach to assess the sufficiency of downstream AKT-regulated molecules in maintaining NMJ stability. These studies will provide novel mechanistic insights into how metabolic signaling interfaces with neuromuscular function, with potential therapeutic implications for conditions like sarcopenia, insulin resistance, and neuromuscular disorders.
2. Understanding the Molecular Mechanisms maintenance of lean mass in Obesity and Aging: Skeletal muscle insulin resistance is a hallmark of metabolic disorders such as obesity and type 2 diabetes (T2D), particularly in aging populations. Sarcopenia, characterized by the progressive loss of muscle mass and function, increases the risk of metabolic diseases, with a more pronounced impact in the context of obesity, termed sarcopenic obesity. This condition represents a major public health concern due to its profound impact on mobility, metabolism, and overall health-span. Using genetic mouse models and human translational studies, we are applying single-cell transcriptomics, phosphoproteomics, and metabolic assays to decipher the signaling pathways mediating the maintenance of lean mass during obesity and sarcopenic obesity.
3. Gut-Muscle Axis: Investigating the Role of the Microbiome in Muscle physiology: Emerging evidence suggests that gut microbiota composition influences skeletal muscle physiology through microbial-derived metabolites, inflammatory mediators, and gut-derived hormones. My lab is spearheading a gut-muscle axis project to explore the impact of microbiome alterations on muscle strength, insulin sensitivity, and metabolic flexibility.
4. Mitochondrial health assessment in health and disease: This project aims to understand the mechanism for mitochondrial dysfunction in both health and disease conditions.