Jeffrey Hord, Ph.D.

The current focus of Dr. Hord's Muscle Resilience Laboratory is to investigate the connection between the muscle cell membrane (i.e., sarcolemma) and the extracellular matrix (ECM), and how this relationship contributes to maintaining muscle fiber homeostasis. We aim to understand the factors involved in development, maintenance, repair, and regeneration of muscle. More specifically, we are examining the roles of the transmembrane receptor dystroglycan (DG) in excitation-contraction coupling and tissue repair. The broad goal of our current research is to determine the importance of the linkage between DG and the ECM in skeletal muscle and cardiac muscle.

In the Muscle Resilience Laboratory, we investigate a subset of neuromuscular diseases known as dystroglycanopathies. The dystroglycanopathies are caused by genetic mutations of DG or mutation of one of over 18 known genes involved in the modification of DG resulting in impaired or non-functional DG. DG is a protein embedded into the cell membrane that links the ECM outside of the cell to the cytoskeleton on the inside of the cell. Therefore, disruption of DG results in interruption of the extracellular-to-intracellular connection. Patients with the disease will have skeletal muscle weakness, which may be accompanied by brain and eye dysfunction. Clinical presentation of the disease can vary widely in severity, with early and late onset having been described. The primary known cause of death is cardio-respiratory complications, which includes sudden cardiac death. 

A barrier in our understanding of the dystroglycanopathies and evaluation of treatments has been the lack of preclinical animal models of the diseases. Dr. Hord and colleagues previously developed multiple mouse lines that model the symptoms and progression of human dystroglycanopathies. Our recent and ongoing studies will allow us to build upon our previous research and help us lead the charge in efforts to understand the dystroglycanopathies and assess treatment strategies. Results from our studies will provide new insights into pathogenesis, disease mechanisms, and evaluation of therapeutic strategies for those affected by the disease. Our mouse models will also facilitate basic science discoveries centered around the many roles of DG in healthy muscle tissue. 

To address our research questions, we utilize genetic mouse models, a combination of in vivo and ex vivo experiments, in addition to downstream biochemical, molecular biology, and microscopy techniques. These approaches will allow us to identify the factors that regulate muscle resilience, delineate the biochemical functions and biophysical properties associated with striated muscle repair and recovery. Ultimately, we aim to translate our findings to prevent or improve pathological conditions affecting striated muscle.