Targeting glutathione metabolism to shape blood and lymphatic vessel growth, regression and survival

• Applicant: Professorin Sofia Iris Bibli, Ph.D.
• Subject Area: Cardiology, Angiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 552773310

Blood and lymphatic vessels intricately sustain life by facilitating processes like oxygen and nutrient delivery, waste removal, tissue repair, and immune responses. These vascular systems are no longer considered only as transporting and responsive interfaces; they also play fundamental roles in organismal resilience. Despite their vital functions, many questions about the behavior of endothelial cells, the building blocks of these vessels, remain unanswered. While significant strides have been made in understanding the behavior of blood endothelial cells in processes like vessel growth, regression, and responses to injury, the same cannot be said for the lymphatic endothelial cells. This knowledge gap underscores the importance of initiatives like the proposed project, which aims to unravel the complexities of vascular dynamics. Our preliminary data highlight the metabolic diversity of glutathione-mediated effects in both blood and lymphatic endothelial cells, emphasizing the need to investigate glutathione oxidation's role in vascular growth and regression. As such, here we aim to unravel the impact of glutathione bioavailability on blood and lymphatic growth and investigate the molecular pathways that are responsible for each organotypic vascular response. Our project focuses on three aims: firstly, identifying how glutathione oxidation influences endothelial cell development, regression, and injury responses in both blood and lymphatic vessels; secondly, characterizing glutathione as a regulator of redox-related death signals and as a novel interactor of the endothelial proteome; and finally, identifying potential therapeutic approaches targeting glutathione oxidation to enhance vascular regeneration post-injury. By elucidating the role of glutathione, our study seeks to provide new insights into endothelial cell biology and its impact on vascular development and injury responses. Understanding these molecular mechanisms could pave the way for targeted therapies for vascular regeneration, offering promising treatments for cardiovascular diseases, cancer, and other vascular-related conditions.

• DFG Programme: Research Grants