Associate Professor, Neurology, University of North Carolina
Abstract: Our research is focused on mechanisms that underlie multisystem proteinopathies characterized by the formation of protein aggregates in the brain, spinal cord, and muscle. Though these are different cell types and, of course, lead to clinically distinct syndromes, the pathogenic mechanisms at play have surprisingly similar themes. For example, protein aggregation is at the heart of motor neuron degeneration in amyotrophic lateral sclerosis (ALS), but is also implicated in various forms of dementia and even muscle myopathies, all leading to cell-type specific vulnerabilities. We seek to uncover these molecular pathways, using both global and protein-targeted approaches, and to understand how and why the formation of toxic aggregates has emerged as the defining hallmark of these disorders. We use any approaches that address these problems including cell biology, biochemistry, proteomics, genetics, and in vivo animal modeling. Our work has raised the intriguing possibility of targeting specific post-translational modifications (PTMs) to suppress pathology in both disease scenarios and possibly during the normal aging process itself. Ongoing characterization of newly generated mouse models will be discussed, with the hopes that these new approaches and tools will help guide the development of therapeutics that had not been considered previously.
