Mikkel Skjoldan Svenningsen - Postdoctoral Fellowship 2024

Project summary:
Heart transplantation as a model system: elucidating the effect of a diabetic environment on the human heart proteome

Heart transplantation creates a unique opportunity to study how the local environment impacts a healthy human heart. This project employs cutting edge proteomic methods to compare changes over time in hearts from nondiabetic donors transplanted into either diabetic or nondiabetic recipients. Through this, we aim to elucidate how a diabetic environment in isolation from other variables impacts the tissue of the heart.

Project Title

Heart transplantation as a model system: elucidating the effect of a diabetic environment on the human heart proteome

Background

Cardiovascular diseases are the leading cause of death in diabetic patients, yet the mechanisms of how diabetes affects the cardiac muscle remains unresolved. Diabetes has a direct effect on heart physiology beyond what can be attributed to other confounding factors, but these impacts are only partially characterised.

Aim

I will employ unbiased proteomic approaches to describe the direct effects of a diabetic environment upon the human heart by utilizing transplantation as a model system. Through this I aim to generate new insights into the pathological effects of diabetes upon the heart applicable to the diabetic population in general.

Methods

As part of routine follow-up of heart transplant recipients, cardiac biopsies are collected at defined time points and preserved for long term storage. Our group has established a workflow to acquire unbiased proteomic profiles of these samples. Using this data, I will analyze protein remodeling in human hearts resulting from diabetes. I will apply a newly established longitudinal statistical workflow to pinpoint diabetes-specific changes in the human heart proteome.