Summary of project PR000427

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR000427. The data can be accessed directly via it's Project DOI: 10.21228/M8VK5D This work is supported by NIH grant, U2C- DK119886.


Project ID: PR000427
Project DOI:doi: 10.21228/M8VK5D
Project Title:Mayo Metabolomics Pilot and Feasibility Award: Deciphering cardioprotective effects of mTOR inhibition via metabolite profiling
Project Summary:Cardiomyopathy is the most common cause for sudden death and heart failure with tremendous public health burden in the U.S. Accumulating evidence from both animal models and clinical studies in human transplant patients suggests that partial inhibition of mechanistic Taget of Rapamycin (mTOR) signaling is a viable avenue for therapeutic intervention. Specifically, we recently showed both compound (rapamycin) treatment and genetic manipulation using a mechanistic Target of Rapamycin (mTOR) haploinsufficient (mTOR+/-) mutant confers cardiac protection against cardiomyopathies of two different etiologies in zebrafish. Mechanistically, antihypertrophy, anti-apoptosis and proautophagy of mTOR inhibition play important roles in this cardioprotection process. Our central hypothesis is that this mTOR inhibition-mediated cardioprotection is conferred by transcription factor EB (TFEB)-regulated autophagy activation. To test this hypothesis, we propose to pursue a systematic metabolite profiling analysis in the heart upon DOX stress under fine-tuned mTOR inhibition. We expect to define metabolite signatures in different types of cardiomyopathy, metabolite signature for the cardioprotective effects of mTOR inhibition, as well as metabolite signatures for TFEB genetic manipulations. These data will be compared with transcriptome studies to prove functions of TFEB signaling in cardioprotective effects of mTOR inhibition, which shall provide a solid foundation for renewing our current RO1 grant aiming to develop mTOR-based therapy for heart failure.
Institute:Mayo Clinic
Last Name:Xu
First Name:Xiaolei
Address:200 First Street SW, Rochester, MN 55905

Summary of all studies in project PR000427

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : Contains raw data)
ST000584 Fasting wildtype, tfeb -/- knockout, and lmna -/- knockout metabolite profiling of adult zebrafish Danio rerio Mayo Clinic MS* 2019-05-15 1 836 Uploaded data (31.9M)