Joel Schilling, MD, PhD

Appointments

Associate Professor of Medicine Cardiovascular Division

Research interests

The role of cytokine signaling in cardiac metabolism.

Our lab is focused on understanding the role of macrophage dysfunction in the pathogenesis of diabetes complications such as poor wound healing, infections, and heart failure.

Molecular mechanisms of lipid toxicity in macrophages

In order to understand how Toll-Like Receptor (TLR) activation in fatty acid (FA)-rich environments produces lysosome dysfunction we have focused on two major questions:

How is macrophage metabolism reprogrammed during activation and how is this altered by the presence of free fatty acids (FFAs)?
What are the pathways downstream of TLR4 and TRIF that combine with FA to mediate toxicity?

To achieve these aims we are utilizing a combination of myeloid specific gene knockouts, macrophage function assays (cytokine release, phagocytosis, survival), cell metabolism assays (Seahorse), and metabolomics approaches. The main objective of this line of research is to identify metabolic pathways in macrophages that could serve as therapeutic targets for diabetes complications and other inflammatory disorders.

Disease models of metabolic complications

Diabetes impairs the body’s response to tissue damage and/or infection and macrophage dysfunction is a likely contributor this phenotype. Clinically relevant manifestations of this phenomenon include poor skin wound healing after injury, increased frequency and severity of urinary tract infections, and heart failure following myocardial infarction or inflammatory injury. To investigate these complications at a cellular and molecular level we have models of skin, cardiac, and infectious injury that we have combined with high-fat diet induced metabolic stress. These in vivo systems are being used to translate molecular findings from our ex vivo work using myeloid specific knockout approaches.