Wel Research Institute projects
The Wel Research Institute is an inter-university life sciences research institute based in Wallonia, Belgium. WELRI aims at promoting scientific excellence in fundamental life sciences research and translating scientific achievements in medical, pharmaceutical and veterinary biotechnology applications.
wel RESEARCH INSTITUTE website
2024
Immunoeradication of persistent cells in AML | Starting Grant
CONTACT : Grégory EHX, Hematology
Acute myeloid leukemia (AML) is the most common and fatal leukemia in adults. Chemotherapy leads to high remission rates, but most patients relapse (survival ~10-40%). Relapse is due to AML blasts (persisters) surviving chemotherapy, and remaining dormant during the remission phase. As these cells are far less numerous than T cells (TCs) during remission, targeting them with immunotherapies would help prevent relapse. However, blasts can evade TC recognition, notably via the expression of immune checkpoint molecules (ICMs).
Our study therefore aims to design immunotherapies targeting persisters by stimulating their recognition by TCs and inhibiting their MCIs. We have designed a proteogenomic method to detect MHC-I peptides specifically expressed by blasts (TSAs) that could serve as vaccination targets. We will use this approach to identify TSAs presented by persisters generated by treating patient AML cells with chemotherapy. To identify critical MCIs, we will conduct a large-scale molecular screen in vitro, followed by more targeted analyses in immunodeficient mice grafted with AML blasts and TCs, or without TCs. Using single-cell RNA sequencing, we will track down persisters in patient bone marrow and characterize their TSA+MCI expression profile to prioritize the most interesting therapeutic targets. Finally, we will test our immunotherapeutic strategy in a preclinical model of AML. Our study could help prevent AML relapse and elucidate the mechanisms of immune evasion of AML cells following chemotherapy.
Translational reprogramming through tRNA modifications in health and diseases | Advanced Grant
CONTACT Alain Chariot, Medical Chemistry
Protein reprogramming enables cancer cells to proliferate and survive longer. Many human pathologies are characterized by deregulation of this reprogramming. Chemical modifications of transfer RNAs regulate the translation of messenger RNAs and therefore play an important role in protein reprogramming. The Elp3 enzyme modifies certain transfer RNAs and is involved in tumor development and metastatic progression. Loss of Elp3 function in hepatocytes leads to post-natal mortality via a blockade of glucose production. We will define the mechanisms by which Elp3 promotes cell differentiation in the liver. We will identify new targets whose translation involves Elp3. Loss of Elp3 function in adipocytes exacerbates weight gain following a high-fat diet. We will identify the molecular players involved in adipocyte hypertrophy whose translation is regulated by Elp3. Finally, we will determine whether loss of Elp3 function in adipocytes sensitizes mice to obesity-related liver cancer. Finally, we will also explore the role of Lepre-1, a hydroxylase that targets proline residues, in tumor development in the intestine. Our work will provide new insights into how chemical modifications of transfer RNAs regulate hepatocyte and adipocyte biology, with important consequences for hepatic metabolism, obesity and obesity-related liver cancer. Our project will also provide a signature of Lepre-1-hydroxylated prolines during tumor development.
2021
2021 selected projects
Translating into cancer: tRNA actors role in cancer stem cells establishment
Francesca Rapino (starting grant)
tRNA epitranscriptomics: a new vulnerability in cancer
Pierre Close (advanced grant)
Systematic eQTL and CMap based identification of IBD predisposing genes and interacting drugs.
Michel Georges (advanced grant)
Deciphering the contribution of the myeloid-epithelial crosstalk to viral-induced exacerbations of chronic airway diseases: an inescapable path towards precision medicine and improved quality of life.
Thomas Marichal (advanced grant)
Cell migration shapes cerebral cortex morphogenesis and function
Laurent Nguyen (advanced grant)
