Determinants of cardioprotection by circulating prohibitin-1 during sepsis

Summary

This research project investigates the role of circulating prohibitin-1 (PHB1) as a cardioprotective 'hepatokine' during sepsis, aiming to understand its mechanisms and validate its potential as a therapeutic target and biomarker for septic cardiomyopathy.

What they want

The project will test the central hypothesis that bloodborne PHB1 mediates a liver-to-heart protective feedback signal during sepsis by enhancing oxidative glucose metabolism and preserving mitochondrial structure and function in the myocardium. This will be achieved through three aims: Aim 1 will determine Nrf2-mediated mechanisms controlling PHB1 secretion in hepatocytes. Aim 2 will identify the mechanisms of cardioprotection conferred by circulating PHB1 during sepsis. Aim 3 will validate serum PHB1 as a predictive biomarker of morbidity and mortality in a cohort of patients with established sepsis (INVACS cohort).

Deliverables

Identification of Nrf2-mediated mechanisms controlling PHB1 secretion in hepatocytes
Identification of mechanisms of cardioprotection conferred by circulating PHB1 during sepsis
Validation of serum PHB1 as a predictive biomarker of morbidity and mortality in sepsis patients

Technical requirements

Gain/loss-of-function approaches in primary cell culture
Clinically relevant mouse models of severe sepsis
Analysis of serum samples from a well-characterized cohort of sepsis patients

Key personnel

Established interdisciplinary research team with complementary and uniquely distinct expertise