Ferroptosis monitoring and targeting in lung ischemia-reperfusion injury from mice to human. 01/11/2023 - 31/10/2025

Abstract

Ferroptosis is an iron-catalyzed form of regulated cell death that occurs due to excessive lipid peroxidation in cellular membranes. Since the discovery in 2012, the high clinical relevance of ferroptosis in e.g. diseases driven by ischemia reperfusion injury (IRI) has boosted the development of ferroptosis therapeutics. To date, the most potent inhibitors in vitro are lipophilic radical trapping antioxidants (RTAs). Our-in house developed and patented candidate lead RTA (UAMC-3203), proved to be superior to the benchmark inhibitors in protecting against organ injury and is therefore considered an excellent drug candidate for clinical translation. At present, the success of transplantation is hampered by the adverse effect of IRI. Supported by multiple preclinical studies, ferroptosis targeting appears a promising strategy to block IRI. We are currently exploring the implementation of ferroptosis inhibitor strategies in the clinical practice of transplantation. Since the in vivo efficacy of UAMC-3203 to block ferroptosis or IRI in the lung is still unclear, we want to monitor ferroptosis during lung IRI in mouse, pig and human and determine its therapeutic potential using UAMC-3203 to block lung IRI in mice and pig.

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  • Research Project

Study the role of cell death in organ injury and/of degeneration. 01/04/2019 - 31/03/2023

Abstract

Unprotected iron can rust due to the attack of oxygen. Similarly, in our body, oxidative stress can kill cells in an iron-dependent way, which can give raise to organ injury or degeneration. This newly discovered type of cell injury or necrosis is referred to as ferroptosis. The study of how this type of cell death works at the molecular levels gains a lot of interest, due to its assumed high clinical relevance. On the one hand, our research focusses on using ferroptosis or 'biological rust' to eradicate cancer such as neuroblastoma using nanomedicinal approaches. On the other hand, blocking ferroptosis using small compounds is intensively investigated in an attempt to interfere with e.g. acute organ failure in intensive care patients or patients with chronic degenerative diseases. This work is imbedded in an interdisciplinary approach and occurs in collaboration with experts and physicians in the field.

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    • Research Project