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Project 1: Provide Mechanistic Insights into the Dystroglycanopathies to Facilitate the Development of Diagnostic and Therapeutic Strategies

Principal Lead: Dr. Kevin P. Campbell

Dr. Campbell is using patient-derived biosamples to investigate the molecular pathogenesis of the dystroglycanopathies, with future studies planned in a dystroglycanopathy mouse model. This research will facilitate the rational design of novel diagnostic and therapeutic strategies.  

This project will investigate the cellular and molecular mechanisms that underly dystroglycanopathies. The proposed studies will establish the relationship between α-DG matriglycan length and laminin-binding properties of matriglycan on α-DG in dystroglycanopathy patient fibroblasts and muscle biopsies. These studies will reveal abnormalities in the post-translational processing of α-DG that result in shorter matriglycan with reduced affinity for laminin leading to muscular dystrophy. The regulation of matriglycan synthesis and its role in the receptor function of α-DG will be established. Finally, the mechanisms underlying the pathophysiology of the dystroglycanopathies will be determined using mouse models with established dystrophic muscle pathology. Collectively, these studies will define the structure of matriglycan that will be required to prevent muscular dystrophy and provide an understanding of the pathological mechanisms underlying dystroglycanopathies, all of which will provide a rationale for the design of novel diagnostics and therapeutic strategies, as well as approaches to monitoring therapeutic engagement and efficacy.

Lab in red tone

Dr. Campbell's Research Laboratory Website

Dr. Campbell's Department of Molecular Physiology & Biophysics Website

Dr. Campbell's HHMI Profile