Assay Development for the Identification of Novel Therapeutics to Treat Heart Failure and Skeletal Muscle Disorders

Faculty Sponsor

Keith Stayrook

College

College of Arts & Sciences (CAS)

Department/Program

Biochemistry

Presentation Type

Poster Presentation

Symposium Date

Summer 7-23-2025

Abstract

This research is a collaborative effort between Pelagos Pharmaceuticals and Valparaiso University. The overall goal is to develop drugs that will halt and/or reverse congestive heart failure and muscle disorders by targeting two nuclear receptors: the Rev-Erb (REV-ERB) receptors and the estrogen-related receptors (ERRs). The work reported here is focused on the treatment of mouse myoblasts (skeletal muscle cell precursors) with potential ERR agonists and then looking for protective changes in gene expression. Previous studies have shown that activation of ERR can enhance mitochondrial function and certain agonists are effective in enhancing muscle function and reducing fibrosis. Additionally, ERR agonists are effective in maintaining oxidative metabolism which helps protect against induced heart failure in mice. These experiments aim to investigate the effects of SLU-PP-332, an ERR agonist, on the gene expression in both differentiated and undifferentiated myoblasts. Changes in gene expression will be assessed using RNA sequencing. Analysis of the gene expression results will be carried out in collaboration with the Valpo U. Dept of Mathematics. The goal of future work will be to characterize changes in gene expression in response to multiple REV-ERB and ERR agonists in order to identify suitable clinical development candidates for treatment of human disease.

Biographical Information about Author(s)

Micah Israel is a rising junior who is majoring in biochemistry. She has previous experience in environmental chemistry research and an interest in microbiology. She has a future interest in medical laboratory science. Brooke Ferkull recently graduated with a degree in Chemistry. She has extensive experience in organic chemistry research. Both were interested in aiding in the research process for the future treatment of heart disease patients.

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