Novel sphingolipid metabolites in myocardial ischemia
Description: Project Narrative This proposal is centered on the hypothesis that cardiac ischemia induces biosynthesis of a group of atypical, toxic sphingolipids that promote cardiomyocyte death. Our evidence indicates ischemia in humans and mouse models upregulates Sptlc3, a novel subunit of serine palmitoyltransferase (SPT), that shifts the substrate preference of SPT, leading to accumulation of atypical, toxic sphingolipids. We will explore whether cardiomyocyte-specific depletion of Sptlc3 attenuates cardiac pathology arising from acute and chronic ischemia in vivo, determine the mechanisms of Sptlc3 regulation, identify specific atypical sphingolipids produced, and determine the cell mechanism(s) by which Sptlc3 products induce apoptosis.
Funding type: research
Funder scheme: R01
Start date: 2020-07-07
End date: 2025-06-30
Investigator: LAUREN ASHLEY COWART
Institution: VIRGINIA COMMONWEALTH UNIVERSITY
Subfield: Molecular Biology
Domain: Life Sciences
Funded outputs count: 21
Funder award ID: R01HL151243
OpenAlex ID: G4830243258