The guiding framework of our research is that healthy muscles lead to healthy aging. Skeletal muscle is the “motor” for movement, but during aging often becomes dysfunctional, leading to mobility limitations and lower life satisfaction. In our lab, we tap into the basic biology of aging and muscle to discover new ways to help older adults keep moving to maintain the independent lifestyle they deserve.

Muscle contraction is carried out by contracting myofibers in an extracellular matrix (ECM). Muscle-resident stromal cells, termed fibro-adipogenic progenitor cells (FAPs), maintain the ECM, equipping it for force transmission. With aging, FAPs lose their homeostatic roles and contribute to the accumulation of their fibrogenic and adipogenic progeny. FAP dysfunction creates a transformed cellular neighborhood that no longer supports muscle function.

Our lab examines muscle-resident FAP dysfunction with aging through a systems-based and cellular lens. We focus on how changes in circulating endocrine signals with age influence muscle-resident FAPs to adopt fibrogenic and adipogenic lineages. The gradual loss of androgens in males and the more rapid loss of estrogens in females during aging leads to breakdowns in endocrine feedback regulatory loops, which dramatically alter the circulating hormonal milieu. Our lab examines how the transition from a “youthful” to an “aged” circulating hormone profile influences the ability of FAPs to support muscle homeostasis using a combination of animal models and cell culture assays.

We also research whether aging impairs FAPs ability to maintain a “youthful” gene regulatory network (GRN) by altering the intracellular biophysical environment. The maintenance of a functional GRN relies on the efficient processing of cell state-specific genetic information, which, at its core, hinges on the ability of the “right” proteins being able to interact with the “right” genes. In our lab, we combine single-cell genomics with super-resolution microscopy to investigate whether aging impairs the ability of FAPs to undergo liquid-liquid phase separation and protect GRN-related genetic material.

My Publications