Award
National Institute of Neurological Disorders and Stroke 1R01NS148075-01
Metabolic regulation of KLHL proteins and targets through O-glycosylation
Recipient
Duke University, Durham, NC, United States
Award Amount
$422,150.00
Ceiling
$422,150.00
Awarded
July 14, 2026
Identifier
1R01NS148075-01
This award funds research on how O-GlcNAcylation regulates KLHL proteins and their substrates, which are involved in neurodegeneration, hypertension, and stroke, aiming to uncover mechanisms and therapeutic opportunities.
Description
The 42-member Kelch-like (KLHL) family of human proteins are critical substrate adapters for E3 ubiquitin ligases, and mutations in KLHL genes cause myriad diseases, including neurodegeneration, hypertension, and cancer. This project aims to elucidate the regulatory mechanisms of KLHL proteins via O-GlcNAcylation and explore therapeutic avenues for neurodegenerative diseases, hypertension, and stroke. The research will characterize the upstream stimuli and downstream effects of O-GlcNAcylation on three model KLHL proteins and their canonical substrates, leveraging interdisciplinary expertise to provide significant insight into proteostasis regulation and potential therapeutic manipulation.