Research

Research Overview

The Szczesny Laboratory integrates biochemical, cellular, in vivo, and ex vivo models to investigate the roles of mitochondria under both physiological and pathological conditions.

Mitochondrial DNA and Inflammatory Response

Our research explores mitochondrial DNA (mtDNA) as both a target and an active mediator linking cellular stress to inflammation. Using multiple experimental models, we have shown that chronic low-level oxidative stress damages mtDNA, leading to its release into the cytoplasm and extracellular space via extracellular vesicles (EVs). Once released, damaged mtDNA interacts with Z-DNA binding protein 1 (ZBP1), activating the TANK-binding kinase 1 (TBK1)/interferon regulatory factor 3 (IRF3) signaling pathway and initiating inflammation. We are currently investigating the contribution of the mtDNA/ZBP1 pathway to inflammatory responses in traumatic brain injury, glaucoma, and lung injury.

Extracellular Vesicles in Cell-to-Cell Communication and as Biomarker Sources

We have identified increased levels of mtDNA in EVs released from various cell types, including neurons and epithelial cells, under chronic oxidative stress and in multiple trauma models. Using both in vitro and in vivo approaches, we are investigating how mtDNA-containing EVs influence immune cell activation across different pathological conditions. Building on our findings of elevated circulating mtDNA-enriched EVs in models of acute lung and traumatic brain injury, we are further characterizing EV composition in biofluids as a potential source of novel biomarkers for tissue injury.