Advances in Bioanalytics and Biomarkers

Therapeutic Targeting of the Unfolded Protein Response to Treat Disease

Tuesday, February 6
11:00 AM - 11:30 AM
Location: 6E

Imbalances in proteostasis are implicated in the onset and pathogenesis of etiologically-diverse disorders including systemic amyloid diseases and ischemic heart disease. Recent work has shown that activation of the unfolded protein response (UPR)-associated transcription factor ATF6 ameliorates imbalances in proteostasis associated with these disorders. However, the lack of pharmacologic approaches to selectively activate ATF6 has limited the development of this approach to intervene in disease. We employed a high-throughput screening approach to identify first-in-class compounds that preferentially activate the ATF6 arm of the UPR. Here, we will describe the mechanism of action for these compounds and highlight their therapeutic potential to correct pathologic imbalances in proteostasis. Collectively, these results will show that pharmacologic ATF6 activation is a broadly applicable strategy to therapeutically intervene in diverse types of disease.

Luke Wiseman

Associate Professor
The Scripps Research Institute

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Therapeutic Targeting of the Unfolded Protein Response to Treat Disease



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