Integrative Muscle Physiology
We focus on understanding how changes at the cellular level in skeletal muscle affect muscle structure and function, and, in turn, how pathological changes in muscle affect cellular processes.
At any given time, muscle tissue houses 5-10 distinct populations of cells, all of which communicate with each other and with their environment to regulate homeostasis and ensure proper muscle function. We know that when something goes awry, as in injury or disease, this communication gets interrupted or misdirected, and cells, such as fibroblasts and adipose progenitors, respond inappropriately by replacing healthy muscle tissue with connective tissue and fat. Yet we don’t fully understand the “language” of these cells, and this keeps us from being able to fully restore cellular interaction and tissue function in many pathologies.
Our main projects are focused on the interaction between muscle and fat. Though much less studied than its “pathological sibling”, fibrosis, the formation of fat in and around muscle is equally prevalent across myopathies. Our research investigates fat’s effect on muscle function and how that effect is regulated at cellular and tissue levels.
Nicole Biltz, DPT Student
Anna Bryniarski, Undergraduate Student
Isacc Na, Undergraduate Student
Current Research Studies
Mapping of Intramuscular Fat to Physiology
Funding Source: Washington University Program in Physical Therapy
A major question standing in the way of understanding fat in muscle is whether this intramuscular adipose tissue (IMAT) is just a feature of disease or whether it independently contributes to poor muscle function. We have developed novel imaging techniques to map IMAT adipocytes in 3-D space to directly correlate IMAT features to physiological function. We use this system to both describe functional effects of IMAT and investigate IMAT-targeted interventions.
Targeting Epimuscular Fat in the Rotator Cuff
Funding Source: Washington University Musculoskeletal Research Center
In the body, fat comes in different “flavors” (e.g. brown and white), that have very different physiological functions – brown fat is metabolically beneficial while excess of white fat is not. A newly discovered fat type, called “beige fat” has features similar to white fat but can be induced to behave, in some ways, like brown fat. The fat that surrounds the muscles of the rotator cuff is a newly identified “depot” of beige fat. We want to know what this means for muscle. Is muscle sensitive to the phenotype of its local fatty environment? Can we engineer the beige fat to behave more like brown fat to improve muscle regeneration and healing following rotator cuff injury? We are examining the mechanisms by which fat might signal muscle in the local environment of the mouse shoulder and combining these findings with studies of human biopsies from rotator cuff surgeries to identify putative therapeutic targets.
Collaborative Research Studies
Defining the Influence of Inflammation in Rotator Cuff Pathology
With Dr. Steve Thomopoulos, Columbia University and Dr. Leesa Galatz, Mount Sinai
The tissues of the rotator cuff degenerate significantly in the context of a chronic tear. This project seeks to investigate the role of inflammation in this degeneration and the potential for therapeutics targeting inflammation to improve tendon-to-bone healing and recovery of muscle function.
Investigating the Role of Intramuscular Adipose Tissue in Diabetic Myopathy
With Dr. Mary Hastings, Washington University, Program in Physical Therapy
Accumulation of intramuscular adipose tissue (IMAT) in the muscles of the distal lower extremity is a prominent feature of Type 2 Diabetes (T2D). It is associated, though not yet causally linked, with reduced muscle strength, poor physical performance and increased risk for falls in individuals with T2D. This project seeks to investigate changes in muscle gene expression local to these IMAT deposits in individuals with T2D to better understand how IMAT might be influencing the muscle environment.