Project description
Protecting the thymus during allogeneic haematopoietic stem cell transplantation
Allogeneic haematopoietic stem cell transplantation (alloHSCT) can cause significant damage to the thymus, impairing its ability to regenerate functional T cells. This is often exacerbated by conditioning regimens and graft-versus-host disease, leading to increased susceptibility to infections and malignancies. The ERC-funded ProtecTHY project aims to protect the thymus from alloHSCT-mediated damage by studying its intrinsic protective mechanisms. The research team will employ an innovative whole organ culture system and a unique collection of human thymus samples to identify how alloHSCT disrupts its structure and assess whether existing clinical treatments can restore thymopoiesis. Findings will pave the way towards new strategies for improved alloHSCT outcomes.
Objective
Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a common, often last-resort treatment for haematological diseases, but it is plagued by long-term morbidity and high mortality. Direct alloHSCT-induced damage to the thymus and subsequent loss of thymopoiesis, ie the production of new T cells, is considered one of the main reasons for these complications. Our limited understanding of how the thymus is damaged during alloHSCT restricts the development of thymus-protecting protocols. The goal of ProtecTHY is to unravel the intrinsic protective mechanisms of the human thymus and assess how alloHSCT affects them, with the ultimate objective of devising measures to prevent thymic damage. We take advantage of an innovative whole organ culture system for the human thymus developed in my laboratory and our extensive pre-existing collection of human thymus tissue samples spanning a diverse age range. ProtecTHY specifically aims to 1) discover how the thymus protects itself from external insults over the course of the human lifetime, 2) reveal how alloHSCT disrupts the human thymus microanatomy and how that damage can be prevented with a cellular therapy, and 3) examine how thymic damage affects the circulating true naive T cells and if existing clinical treatments for alloHSCT complications can restore the loss of thymopoiesis. We will apply state-of-the-art spatial and single-cell multiomics to dissect these protective layers of the thymus both ex vivo and after alloreactive challenge in vitro. Moreover, by testing the effect of treatments already in clinical use, ProtecTHY can resolve their specific mechanisms of action and impact on the thymus. Our results are thus directly translatable to the human condition and can direct future treatments to enhance outcomes following alloHSCT. As a translational immunologist and clinical microbiologist with extensive experience in human thymus research, I am well equipped to uncover the mechanisms of thymic protection.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- social sciences sociology demography mortality
- medical and health sciences clinical medicine transplantation
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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HORIZON.1.1 - European Research Council (ERC)
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(opens in new window) ERC-2024-STG
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00014 Helsinki
Finland
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