Research

Cells modulate their internal stiffness (cortical tension) in response to external forces, such as the stiffness or chemical composition of their extracellular environment.  Poorly understood signaling pathways downstream of mechanical stimulation regulate cell growth, survival and differentiation.  Increased stiffness of the extracellular matrix (ECM) can promote tumor growth or lead to increased size (hypertrophy) of muscles.  Cross-talk between these growth and survival pathways is limits some cancer treatments, resulting in choices between cancer reoccurrence and heart failure.

We study how signaling and cytoskeletal proteins at the plasma membrane participate in cellular responses to extracellular force.  Our major area of interest is how the stiffness of the extracellular matrix causes increased internal stiffness (cortical tension) and, in turn, how increased cortical tension regulates cell growth, survival and differentiation.  With our collaborators, we have linked membrane proteins studied for their roles in muscular dystrophies, e.g. dystrophin, to signaling pathways (FAK, Rac, ERK) understood best in the context of axonal outgrowth and tumor cell migration.  There are similarities and differences between these signaling pathways in tumor cells and fibroblasts versus skeletal muscle and cardiac myocytes, due to cell type-specific protein expression and differential splicing.  In addition to increasing our basic understanding of stiffness-mediated biochemical signaling, a long-term goal of this research is to identify ways to up-regulate myofiber survival in dystrophic muscle.  Another long-term aim is to identify cell type-specific interactions that can be exploited to prevent or treat the cardiac side effects associated with many chemotherapeutics. 

This research is supported by a collaborative R01 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases at the National Institutes of Health with Dr. Elisabeth Barton at the University of Florida Wellstone Muscular Dystrophy Cooperative Research Center.