Federal Grant Award Summary

The University of Texas Health Science Center at Houston received a $390,000 Project Grant from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859), awarded March 1, 2026, with completion scheduled for December 31, 2030. This research project investigates inter-organelle unfolded protein response (UPR) coordination and cellular proteostasis, specifically examining how cells maintain protein homeostasis under stress conditions relevant to aging. The research focuses on understanding communication and coordination mechanisms between organelle-specific UPRs in mitochondria, the endoplasmic reticulum, and the cytosol, with particular emphasis on the previously underexplored interplay between lipid metabolism and protein-folding processes.

The project's central research objective is to elucidate the connection between lipid homeostasis and proteostasis through organelle-to-organelle communication, with a hypothesis that the cardiolipin-to-ceramide lipid ratio is critical for stress response pathway communication across cellular compartments. Preliminary findings from C. elegans and mammalian cell culture systems have demonstrated that mitochondrial UPR can simultaneously activate cytosolic UPR while inhibiting endoplasmic reticulum UPR to enhance cellular resistance to proteotoxic stress. This fundamental research addresses the broader goal of understanding how cells utilize different organelle stress responses to maintain homeostasis, with potential implications for understanding lipid dyshomeostasis in neurodegenerative diseases, cardiovascular disease, diabetes, and cancer.