2025 GIGA Annual Report | 1
2 | 2025 GIGA Annual Report EDITO “Medicine doesn’t end at the hospital; it only begins there. Upon leaving the hospital, the physician must go to his laboratory, and it is there that he will seek, through experiments, to understand what he has observed in his patients.” This plea for experimental medicine, both eloquent and concise, is to the credit of his father, Claude Bernard (1813-1878). However, since the late 1980s, on both sides of the Atlantic, voices have been raised to alert political and scientific authorities to the fact that the career of medical researcher (physician-scientist or clinician-scientist) is more and more neglected and that MD-PhDs were becoming an endangered species. The role of these physician-scientists in an academic hospital and/or in a research institute is indeed very important as they actively drive innovation across a wide range of medical specialties. Moreover, they could use their extensive training to focus their clinical practices on a selected patient population (rare diseases, intractable cancers, …). One can rapidly understand that they play a critical role both in translational medicine and clinical research by adapting biomedical research findings to health care improvements or new applications. About fifteen years ago, the Belgian Royal Academy of Medicine alerted our political and scientific authorities to the danger posed by the scarcity, or even disappearance, of such physician profiles in our university hospitals. Its voice was heeded, notably by the FNRS, which established the career path of clinical researchers by paying young colleagues part-time, thus allowing them to pursue research alongside their clinical work (https://www.facmed.uliege.be/ cms/c_9824204/en/facmed-clinical-researchers). At the University of Liège, we benefit from several valuable elements that are likely to support this clinical research activity: the proximity of the academic hospital to all the research laboratories of the Faculty of Medicine, including, of course, those of the GIGA; the fact that the Faculty of Medicine of the University
2025 GIGA Annual Report | 3 of Liège is complete, that is to say that it brings together all professional training courses that play a role in the context of human health; the growing proximity, particularly in various GIGA research units, to colleagues from the Faculty of Veterinary Medicine. These considerations lead the Faculty of Medicine to set up “Student-Researcher” mandates in 2008 to encourage clinical researcher vocations among young medical students. This initiative was joined by that of the Léon Fredericq Foundation several years ago to occasionaly replace the FNRS to cover half the salary of young doctors who submitted their application to the FNRS and who were well evaluated by the scientific committee but not taken on as a research fellow due to a lack of financial resources at the FNRS. These proactive policies, implemented by the Faculty of Medicine, the University Hospital and the Léon Fredericq Foundation, are bearing fruit. Indeed, in 2021 (the year of the last count in this area), there were 66 clinical researchers at the FNRS in the French Community in Belgium, 25 of whom worked both at the Liège University Hospital and in a GIGA laboratory. If we «normalize» the expected number of clinical researchers we should expect at the Faculty of Medicine by taking into account the number of Master’s medical students, we should have only 14. This promising observation, however, should not lead us to rest on our laurels. It is indeed essential to continue integrating clinicians into our research laboratories. Moreover, it is also crucial, at both the Faculty and University Hospital level, to ensure that these clinical researchers remain motivated in both their activities after completing their doctorate. It is indeed the responsibility of a Faculty of Medicine and a University Hospital to transform the alarming observation of a few years ago, namely that clinical researchers are an endangered species, into a new encouraging observation: that clinical researchers are an evolving species. Bernard Rogister, Vice-Dean of the Faculty of Medicine Full Professor ULiège Head of the Laboratory of Nervous system disorders and therapy Treasurer of the Léon Fredericq Foundation
4 | 2025 GIGA Annual Report OUR DIR General Director Head of the Laboratory Developmental Neurobiology Neuroscience BRIGITTE MALGRANGE Scientific Director Head of the Laboratory of Molecular Regulation of Neurogenesis Neuroscience LAURENT NGUYEN
2025 GIGA Annual Report | 5 RECTION TEAM Medical Director Head of the Laboratory of Rheumatology Immunobiology CLIO RIBBENS Administrative Director Head of the administration SANDRINA EVRARD
6 | 2025 GIGA Annual Report OUR DOMAINS CANCER PIs & Administrators Arnaud Blomme, Michael Herfs, Ingrid Struman PIs Akeila Bellahcène, Vincent Bours, Didier Cataldo, Alain Chariot, Pierre Close, Alain Colige, Christophe Deroanne, Christine Gilles, Stéphanie Herkenne, Pascale Hubert, Guy Jérusalem, Claire Josse, Erik Maquoi, Denis Mottet, Carine Munaut, Agnès Noel, Marie-Julie Nokin, Christel Péqueux, Olivier Peulen, Francesca Rapino, Nor Eddine Sounni, Marianne Voz, Luc Willems PIs & Administrators Julie Bakker, Vincent Bonhomme, Gilles Vandewalle PIs Christine Bastin, Fabienne Collette, Charlotte Cornil, Laurence Delacroix, Athena Demertzi, Dominique Engel, Ira Espuny Camacho, Rachelle Franzen, Gaetan Garraux, Olivia Gosseries, Sophie Laguesse, Jean-Marc Lassance, Didier Ledoux, Brigitte Malgrange, Pierre Maquet, Virginie Neirinckx, Laurent Nguyen, Anne-Simone Parent, Christophe Phillips, Bernard Rogister, Christina Schmidt, Vincent Seutin, Aurore Thibaut, Renaud Vandenbosch, Audrey Vanhaudenhuyse NEUROSCIENCE
2025 GIGA Annual Report | 7 IMMUNOBIOLOGY PIs & Administrators Christophe Desmet, Grégory Ehx, Thomas Marichal PIs Frédéric Baron, Fabrice Bureau, Jo Caers, Dominique de Seny, Emmanuel Dejardin, Nathalie Esser, Julien Guiot, Nathalie Jacobs, Marielle Lebrun, Sylvie Legrand, Edouard Louis, Renaud Louis, Marie-Alice Meuwis, Catherine Moermans, Clio Ribbens, Catherine Sadzot PIs & Administrators Franck Dequiedt, Liesbet Geris, Julien Hanson PIs Vincent Bours, Carole Charlier, Thomas Desaive, Tom Druet, Thibault Gendron, Michel Georges, Roland Hustinx, Marjorie Lienard, Philippe Morimont, Bernard Peers, Souad Rahmouni, Stephane Schurmans, Alain Seret, Jean-Claude Twizere, Anne Van den Broeke, Kristel Van Steen, Nadia Withofs MOLECULAR & COMPUTATIONAL BIOLOGY PI & Administrator Patrizio Lancellotti PIs Olivier Detry, Pierre Drion, François Jouret, Patricia Lassaux, Cécile Oury, Vincent Tchana-Sato METABOLISM & CARDIOVASCULAR BIOLOGY
8 | 2025 GIGA Annual Report KEY NUMBERS 667 members 60% women/40%men Researchers from abroad 37 nationalities
2025 GIGA Annual Report | 9 667 members 60% women - 40% men 37 nationalities - 17% foreigners 522 publications 44 PhD theses defended 401 active research projects 122 new projets in 2024 54 partner countries in the ongoing projects 101 Academics & Permanent Researchers 50 Clinicians (academics or not) in 2024 161 Contract scientists & Postdocs 243 PhD Students 112 Technical & Administrative Staff
10 | 2025 GIGA Annual Report Fundings In 2024 401 active research projects 122 new projets 54 partner countries in the ongoing projects All the active research projects in 2024 = 26 Mio € Wallonie/Bxl Federation Walloon Region ULiège UE Contracts Donations Federal FEDER/ERDF Others 23% 17% 15,5% 13% 12% 8% 5% 4%2,5%
2025 GIGA Annual Report | 11 SPW EER wishes to respond to the comments* made in the 2023 report by Professor Michel GEORGES. The full right of reply has been added to the 2023 report. It addresses inaccuracies in an interview with Professor Michel Georges, highlights the financial support GIGA has received from the Walloon Region, including over €61 million from ERDF funds between 2004 and 2024. The response refutes claims about the inefficiency of SPW-Research, emphasising the transparency and regularity of its funding calls. It also clarifies that the ERDF funds are not meant for structural financing but for funding projects with a positive cost-benefit ratio for the socio-economic development of Wallonia. The right of reply also clarifies SPW-Research’s procedures and the importance of economic valorisation in research funding. Finally, it takes stock of recent constructive discussions between the new heads of GIGA and SPW-EER. *Editor’s note : personal comments
12 | 2025 GIGA Annual Report SOME OF THE BEST 2024 PUBLICATIONS
2025 GIGA Annual Report | 13 Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with poor survival rates due to late diagnosis and lack of effective treatments. In this study, researchers from the Laboratory of Metastases Research, led by Olivier Peulen, investigated myoferlin, an oncoprotein overexpressed in PDAC, to understand its role in cancer cell behavior and mitochondrial dynamics. Using two PDAC cell lines (Panc-1 and MiaPaCa-2), the team explored myoferlin localization, its presence in mitochondria-associated membranes, and its role in mitochondrial calcium transfer. Results indicated that myoferlin is part of mitochondria- associated membranes and its silencing reduces mitochondrial calcium levels upon stimulation, likely through its interaction with inositol 1,4,5-triphosphate receptors. This work sheds light on myoferlin’s involvement in cancer biology and mitochondrial dynamics, offering insights into potential therapeutic targets. IDENTIFICATION OF MYOFERLIN AS A MITOCHONDRIA-ASSOCIATED MEMBRANES COMPONENT REQUIRED FOR CALCIUM SIGNALING IN PDAC CELL LINES Anania S, Farnir M, Peiffer R, Boumahd Y, Thiry M, Agirman F, Maloujahmoum N, Bellahcène A, Peulen O. Cell Commun Signal. 2024 Feb 17;22(1):133. doi: 10.1186/s12964-024-01514-z. p LINKS | Publication on ORBI | Olivier Peulen
14 | 2025 GIGA Annual Report Lijing Tang and colleagues from the Unit of Animal Genomics have developed a molecular method to quantify the transposition rate of endogenous retroviruses (ERVs) in bovine sperm, shedding new light on their life cycle. ERVs, viral remnants embedded in the genome, typically become inactive over time. However, the team identified an ERV family in cattle still undergoing expansion, capable of generating new insertions. By analyzing 430 bulls, they found that the de novo transposition rate (dnTR) varies significantly between individuals, averaging one new insertion per 150 sperm cells. A genome-wide association study revealed eight genetic loci influencing this rate, with four linked directly to polymorphic ERVs. Interestingly, while «C-type» ERVs (competent for replication) drive transposition, most new insertions come from «D-type» ERVs, which hijack the replication machinery. This discovery provides key insights into ERV dynamics and their evolutionary decline. GWAS REVEALS DETERMINANTS OF MOBILIZATION RATE AND DYNAMICS OF AN ACTIVE ENDOGENOUS RETROVIRUS OF CATTLE Tang L, Swedlund B, Dupont S, Harland C, Costa Monteiro Moreira G, Durkin K, Artesi M, Mullaart E, Sartelet A, Karim L, Coppieters W, Georges M, Charlier C. Nat Commun. 2024 Mar 9;15(1):2154. doi: 10.1038/s41467-024-46434-1. p LINKS | News GIGA | Publication on ORBI | Carole Charlier
2025 GIGA Annual Report | 15 Awareness of dependence in daily activities plays a significant role in the evolution of neurodegenerative dementias. Christine Bastin, from the Laboratory of Aging & Memory, led a study investigating how participant and caregiver assessments of dependence could predict changes in autonomy over one year. The study included mildly demented participants diagnosed with Alzheimer’s disease (AD, n = 186) and frontotemporal dementia (FTD, n = 29). The research tool assessed dependence in 98 daily activities and caregiver burden. Discrepancy scores between patient and caregiver assessments of dependence were calculated to evaluate awareness. Results showed that FTD patients had lower awareness of dependence than AD patients. Both groups benefited from cognitive rehabilitation, with a 25% decrease in dependence and reduced caregiver burden. In the AD group, both caregiver and participant assessments at baseline were positively correlated with greater dependence after one year, highlighting the importance of both perspectives in understanding the evolution of dementia and the benefit of care. AWARENESS AND COGNITIVE REHABILITATION IN ALZHEIMER’S DISEASE AND FRONTOTEMPORAL DEMENTIA Salmon E, Lekeu F, Quittre A, Godichard V, Olivier C, Wojtasik V, Bastin C. Alzheimers Dement (N Y). 2024 Apr 16;10(2):e12469. doi: 10.1002/trc2.12469. p LINKS | Publication on ORBI | Christine Bastin
16 | 2025 GIGA Annual Report Puberty is a critical period for the development of female sexual behavior, and stress during this phase can have lasting effects. A study led by Julie Bakker at the Laboratory of Neuroendocrinology found that chronic pubertal stress permanently impaired sexual performance in female mice without affecting sexual preference. This disruption was linked to reduced activation of nitric oxide-producing neurons in the ventromedial hypothalamus, a brain region essential for female sexual behavior. Notably, these neurons, which typically respond to male olfactory cues, showed diminished activation in stressed females. Treating affected mice with a nitric oxide donor partially restored sexual behavior, highlighting the importance of this neural pathway. These findings underscore puberty as a sensitive window in which stress can alter brain circuits involved in sexual function, potentially leading to long-term consequences for reproductive health STRESS DURING PUBERTAL DEVELOPMENT AFFECTS FEMALE SOCIOSEXUAL BEHAVIOR IN MICE Bentefour Y, Bakker J. Nat Commun. 2024 Apr 30;15(1):3610. doi: 10.1038/s41467-024-47300-w. p LINKS | News GIGA | Publication on ORBI | Julie Bakker
2025 GIGA Annual Report | 17 Grégory Ehx (WELRI Investigator) and his team at the Laboratory of Hematology, in collaboration with Canadian researchers, have uncovered a key limitation of azacitidine (AZA), a firstline treatment for elderly acute myeloid leukemia (AML) patients. AZA is known to reactivate silenced genes, including endogenous retroelements (EREs), ancient viral sequences in our DNA. While ERE activation triggers antiviral immune responses that hinder leukemia progression, the team discovered that AZA simultaneously induces autophagy, a cellular recycling process that degrades EREs before they can be presented to the immune system. By inhibiting autophagy, they restored the ability of leukemia cells to present ERE-derived peptides, enhancing immune recognition. Moreover, AML patients with high ERE expression but low autophagy showed stronger T-cell responses. These findings, published in Leukemia, suggest that combining AZA with autophagy inhibitors—many of which are already clinically approved—could improve AML treatment outcomes. AUTOPHAGY DEGRADES IMMUNOGENIC ENDOGENOUS RETROELEMENTS INDUCED BY 5-AZACYTIDINE IN ACUTE MYELOID LEUKEMIA Noronha N, Durette C, Cahuzac M, E Silva B, Courtois J, Humeau J, Sauvat A, Hardy MP, Vincent K, Laverdure JP, Lanoix J, Baron F, Thibault P, Perreault C, Ehx G. Leukemia. 2024 May;38(5):1019-1031. doi: 10.1038/s41375-024-02250-6. p LINKS | News GIGA | Publication on ORBI | Grégory Ehx
18 | 2025 GIGA Annual Report Eosinophils play diverse roles in immunity, tissue repair, and metabolism, yet their development remains poorly understood. Christophe Desmet and his team at the Laboratory of Cellular and Molecular Immunology used advanced single-cell techniques to map eosinophil maturation in both mice and humans. Their research challenges long-standing assumptions about Interleukin-5 (IL-5), a key cytokine in eosinophilia. Rather than directly promoting eosinophil maturation, IL-5 prolongs an intermediate phase where eosinophils multiply, thus increasing their numbers. Blocking IL-5, a strategy used in treating eosinophilic diseases like asthma, reduces eosinophilia by preventing this amplification step. The study provides valuable resources and insights into eosinophil biology, paving the way for improved therapeutic strategies. SINGLE-CELL PROTEOMICS AND TRANSCRIPTOMICS CAPTURE EOSINOPHIL DEVELOPMENT AND IDENTIFY THE ROLE OF IL-5 IN THEIR LINEAGE TRANSIT AMPLIFICATION Jorssen J, Van Hulst G, Mollers K, Pujol J, Petrellis G, Baptista AP, Schetters S, Baron F, Caers J, Lambrecht BN, Dewals BG, Bureau F, Desmet CJ p LINKS | News GIGA | Publication on ORBI | Christophe Desmet Immunity. 2024 Jul 9;57(7):1549-1566.e8. doi: 10.1016/j.immuni.2024.04.027.
2025 GIGA Annual Report | 19 Melanoma, one of the deadliest skin cancers, remains a major therapeutic challenge due to its ability to develop resistance to targeted therapies, ultimately leading to treatment failure and disease progression. Pierre Close (WELRI Investigator) and his team at the Laboratory of Cancer Signaling investigated the molecular mechanisms underlying this resistance and identified a crucial role for the enzyme VARS (Valyl tRNA synthetase) in sustaining the survival of therapy-resistant melanoma cells. Using protein and RNA sequencing data, the researchers demonstrated that resistant cells undergo a profound reprogramming of their protein synthesis machinery, shifting their reliance onto VARS. By inhibiting this enzyme, they were able to re-sensitize melanoma cells to treatment, effectively reversing resistance. These findings highlight the importance of transfer RNA regulation in acquired drug resistance and suggest that targeting VARS could enhance the efficacy of existing therapies. This discovery paves the way for new treatment strategies aimed at overcoming resistance mechanisms in melanoma, offering fresh hope for patients facing limited therapeutic options. VALINE AMINOACYL-TRNA SYNTHETASE PROMOTES THERAPY RESISTANCE IN MELANOMA El-Hachem N, Leclercq M, Susaeta Ruiz M, Vanleyssem R, Shostak K, Körner PR, Capron C, Martin-Morales L, Roncarati P, Lavergne A, Blomme A, Turchetto S, Goffin E, Thandapani P, Tarassov I, Nguyen L, Pirotte B, Chariot A, Marine JC, Herfs M, Rapino F, Agami R, Close P. p LINKS | News GIGA | Publication on ORBI | Pierre Close Nat Cell Biol. 2024 Jul;26(7):1154-1164. doi: 10.1038/s41556-024-01439-2.
20 | 2025 GIGA Annual Report Tom Druet from the Unit of Animal Genomcis participated to a study that explored the genetic history and composition of feral cattle on Amsterdam Island. The population, founded by just five animals that were abandoned on this remote and inhospitable island in the late 19th century, showed contributions from European taurine and Indian Ocean Zebu ancestry. The research revealed an intense but brief bottleneck during the population’s founding, followed by moderate genetic diversity reduction despite high inbreeding. This bottleneck resulted in high drift and slight relaxation of purifying selection on mildly deleterious variants, but no significant purging of harmful variants. The cattle’s success in the harsh environment was attributed to preadaptation from their European taurine ancestry, contradicting theories of insular dwarfism. The genome scan revealed selection footprints in genes related to nervous system function, indicating behavioral changes due to rapid feralization. The findings offer insights into population establishment, feralization, and genetic adaptation in challenging environments and raise ethical questions for conservation. GENOMIC RECONSTRUCTION OF THE SUCCESSFUL ESTABLISHMENT OF A FERALIZED BOVINE POPULATION ON THE SUBANTARCTIC ISLAND OF AMSTERDAM Gautier M, Micol T, Camus L, Moazami-Goudarzi K, Naves M, Guéret E, Engelen S, Lemainque A, Colas F, Flori L, Druet T. Mol Biol Evol. 2024 Jul 3;41(7):msae121. doi: 10.1093/molbev/msae121 p LINKS | Publication on ORBI | Tom Druet
2025 GIGA Annual Report | 21 Targeted therapies have significantly improved outcomes for patients with BRAF-mutant lung adenocarcinoma, but the emergence of drug-tolerant and resistant cancer cells limits long-term success. To address this challenge, Marie-Julie Nokin and her team conducted an in-depth investigation into the adaptive mechanisms that allow these cells to survive treatment. Using whole-genome CRISPR screening and RNA sequencing, the researchers uncovered distinct vulnerabilities in both early drug-tolerant and fully resistant cancer cells. Their findings reveal that drug-tolerant cells experience oxidative stress and lipid peroxidation, rendering them particularly susceptible to ferroptosis upon inhibition of GPX4, a key antioxidant enzyme. In contrast, resistant cells reactivate the MAPK pathway, reinforcing their antioxidant defenses and promoting survival. Importantly, the team identified that histone deacetylase (HDAC) inhibitors significantly reduce the viability of resistant cells, offering a promising therapeutic avenue to overcome resistance. These insights pave the way for novel treatment strategies that could enhance the efficacy of existing therapies, ultimately improving patient care and extending treatment response in BRAF-mutant lung adenocarcinoma. IN VIVO VULNERABILITIES TO GPX4 AND HDAC INHIBITORS IN DRUG-PERSISTENT VERSUS DRUG-RESISTANT BRAFV600E LUNG ADENOCARCINOMA Nokin MJ, Darbo E, Richard E, San José S, de Hita S, Prouzet-Mauleon V, Turcq B, Gerardelli L, Crake R, Velasco V, Koopmansch B, Lambert F, Xue JY, Sang B, Horne J, Ziemons E, Villanueva A, Blomme A, Herfs M, Cataldo D, Calvayrac O, Porporato P, Nadal E, Lito P, Jänne PA, Ricciuti B, Awad MM, Ambrogio C, Santamaría D; Bolero Consortium. Cell Rep Med. 2024 Aug 20;5(8):101663. doi: 10.1016/j.xcrm.2024.101663. p LINKS | News GIGA | Publication on ORBI | Marie-Julie Nokin
22 | 2025 GIGA Annual Report Macrophages play a crucial role in immune defense and tissue repair, yet their contributions to lung regeneration following viral infections remain incompletely understood. In a study led by Thomas Marichal (WELRI Investigator) and Coraline Radermecker at the Laboratory of Immunophysiology, researchers identified a previously unrecognized population of macrophages that are transiently recruited during the recovery phase of lung infections. These macrophages interact closely with alveolar progenitor cells to stimulate the regeneration of alveoli, the air sacs essential for gas exchange. Unlike resident alveolar macrophages, this newly identified subset displays atypical molecular markers, which likely contributed to their prior oversight in research. Their temporary yet significant role in lung healing suggests they may serve as a key therapeutic target for promoting tissue repair and preventing long-term pulmonary complications. By harnessing the regenerative potential of these macrophages, future therapies could help mitigate the consequences of severe respiratory infections, such as those caused by influenza or COVID-19, ultimately improving patient outcomes. RECRUITED ATYPICAL LY6G+ MACROPHAGES LICENSE ALVEOLAR REGENERATION AFTER LUNG INJURY Ruscitti C, Abinet J, Maréchal P, Meunier M, de Meeûs C, Vanneste D, Janssen P, Dourcy M, Thiry M, Bureau F, Schneider C, Machiels B, Hidalgo A, Ginhoux F, Dewals BG, Guiot J, Schleich F, Garigliany MM, Bellahcène A, Radermecker C, Marichal T. Sci Immunol. 2024 Aug 2;9(98):eado1227. doi: 10.1126/sciimmunol.ado1227 p LINKS | News GIGA | Publication on ORBI | Thomas Marichal
2025 GIGA Annual Report | 23 THE ISLET TISSUE PLASMINOGEN ACTIVATOR/PLASMIN SYSTEM IS UPREGULATED WITH HUMAN ISLET AMYLOID POLYPEPTIDE AGGREGATION AND PROTECTS BETA CELLS FROM AGGREGATION-INDUCED TOXICITY Esser N, Hogan MF, Templin AT, Akter R, Fountaine BS, Castillo JJ, El-Osta A, Manathunga L, Zhyvoloup A, Raleigh DP, Zraika S, Hull RL, Kahn SE. Islet amyloid deposition and reduced beta-cell mass are pathological hallmarks of type 2 diabetes. Aggregation of human islet amyloid polypeptide (hIAPP), the main peptide component of islet amyloid deposits in humans, is toxic to beta cells. A study led by Nathalie Esser from the Laboratory of Immunometabolism & Nutrition delineated a new role for the fibrinolytic system in modulating islet amyloidogenesis. Results showed a local tissue plasminogen activator (tPA)/plasmin system is specifically upregulated in vitro in amyloid-laden hIAPP transgenic mouse and human islets from donors with type 2 diabetes. Results also demonstrated that plasmin is an hIAPP-degrading enzyme that protects beta cells from hIAPP-induced toxicity. The study concluded that the tPA/ plasmin system could serve a protective function to limit islet amyloid deposition and its cytotoxic effects, suggesting that increasing tPA/plasmin activity could help prevent beta cell loss in type 2 diabetes. Diabetologia. 2024 Sep;67(9):1897-1911. doi: 10.1007/s00125-024-06161-0. p LINKS | Publication on ORBI | Nathalie Esser
24 | 2025 GIGA Annual Report REGIONAL RESPONSE TO LIGHT ILLUMINANCE ACROSS THE HUMAN HYPOTHALAMUS Campbell I, Sharifpour R, Balda Aizpurua JF, Beckers E, Paparella I, Berger A, Koshmanova E, Mortazavi N, Read J, Zubkov M, Talwar P, Collette F, Sherif S, Phillips C, Lamalle L, Vandewalle G. Exposure to bright light can enhance wakefulness and cognitive performance by influencing hypothalamic activity, according to a study led by Gilles Vandewalle at the Sleep Laboratory. Using 7 Tesla MRI, researchers examined how different light intensities affected the hypothalamus while 26 healthy adults performed auditory cognitive tasks. They found that higher illuminance increased activity in the posterior hypothalamus but decreased activity in anterior and inferior regions. Notably, improved performance on an executive task correlated with reduced posterior hypothalamic activity, suggesting that other brain regions contribute to light-induced cognitive benefits. These findings deepen our understanding of how light modulates brain function and could inform therapeutic lighting strategies to enhance alertness and cognitive function. Elife. 2024 Oct 28;13:RP96576. doi: 10.7554/eLife.96576. p LINKS | News GIGA | Publication on ORBI | Gilles Vandewalle
2025 GIGA Annual Report | 25 THE IMPACT OF CHARCOT-LEYDEN CRYSTAL PROTEIN ON MESOTHELIOMA CHEMOTHERAPY: TARGETING EOSINOPHILS FOR ENHANCED CHEMOSENSITIVITY Willems M, Hamaidia M, Fontaine A, Grégoire M, Halkin L, Vilanova Mañá L, Terres R, Jamakhani M, Deshayes S, Brostaux Y, Heinen V, Louis R, Duysinx B, Jean D, Wasielewski E, Scherpereel A, Blanquart C, Willems L. . Mesothelioma (MPM) patients show poor outcomes, with clinical evidence linking eosinophil count to overall survival and chemotherapy response. Researchers from the Laboratory of Cellular and Molecular Epigenetics, led by Luc Willems, investigated the role of eosinophil-derived factors in mesothelioma response to chemotherapy. They found that eosinophil-conditioned supernatants inhibited apoptosis in mesothelioma cells exposed to cisplatin and pemetrexed, both in 2D cultures and spheroids. The anti-apoptotic effect involved interactions with Charcot-Leyden Crystal protein or Galectin-10 (CLC-P/Gal10), and recombinant CLC-P/ Gal10 mimicked this effect. In a preclinical mouse model, eosinophilia altered chemotherapy response, but not tumor growth. Pre-treatment with anti-Siglec-F antibody restored chemotherapy effectiveness. This study provides mechanistic insight into the link between eosinophils and poor mesothelioma outcomes, opening avenues for potential therapeutic strategies. EBioMedicine. 2024 Nov;109:105418. doi: 10.1016/j.ebiom.2024.105418. p LINKS | Publication on ORBI | Luc Willems
26 | 2025 GIGA Annual Report EXTERNAL VALIDATION OF SERUM BIOMARKERS PREDICTING SHORT-TERM AND MID/LONG-TERM RELAPSE IN PATIENTS WITH CROHN’S DISEASE STOPPING INFLIXIMAB Pierre N, Huynh-Thu VA, Baiwir D, Mazzucchelli G, Fléron M, Trzpiot L, Eppe G, De Pauw E, Laharie D, Satsangi J, Bossuyt P, Vuitton L, Vieujean S, Colombel JF, Meuwis MA, Louis E; GETAID and the SPARE-Biocycle research group. Researchers, including Nicolas Pierre from the Laboratory of Translational Gastroenterology, have confirmed distinct blood protein profiles predicting short-term and mid/long-term relapse in Crohn’s disease patients discontinuing anti-TNF-α therapy. This study validates findings from a previous cohort (STORI) using an independent patient group (SPARE), strengthening their potential to guide treatment decisions. By identifying early signs of disease reactivation, these biomarkers could help personalize therapy, reducing unnecessary risks and costs. Conducted through international collaboration, the research leveraged advanced proteomics technology to analyze blood samples from 300 patients, offering a precise and innovative approach to Crohn’s disease management. Gut. 2024 Nov 11;73(12):1965-1973. doi: 10.1136/gutjnl-2024-332648. p LINKS | News GIGA | Publication on ORBI | Nicolas Pierre
2025 GIGA Annual Report | 27 APOMORPHINE FOR PROLONGED DISORDERS OF CONSCIOUSNESS: A MULTIMODAL OPEN-LABEL STUDY Sanz LRD, Lejeune N, Szymkowicz E, Bonin EAC, Panda R, Sala A, Thibaut A, Huerta-Gutierrez R, Dardenne N, Dikenstein D, Van Goethem S, Ledoux D, Hustinx R, Stender J, Farber NM, Zafonte RD, Schiff ND, Laureys S, Gosseries O. A study led by Leandro Sanz and Olivia Gosseries from the Coma Science Group explores the potential of apomorphine to aid recovery in patients with severe brain injuries and impaired consciousness. Thirteen patients received subcutaneous apomorphine treatment for 30 days, showing significant improvements in behavioral responses, including visual pursuit and command-following, compared to a control group. These gains persisted even after treatment cessation. Using EEG, and PET scans, the researchers found enhanced brain connectivity and metabolism in treated patients. This preliminary study shows promising results for apomorphine in post-coma recovery. While further trials are needed, the study highlights apomorphine as a potential therapeutic for disorders of consciousness. EClinicalMedicine. 2024 Nov 15;78:102925. doi: 10.1016/j.eclinm.2024.102925 p LINKS | News GIGA | Publication on ORBI | Olivia Gosseries
28 | 2025 GIGA Annual Report THE CIRCADIAN BRAIN AND COGNITION Cajochen C, Schmidt C. Christina Schmidt, Laboratory of Sleep and Chronobiology, has co-authored a review published in the Annual Review of Psychology with Christian Cajochen, Director of the Center for Chronobiology at the University of Basel, Switzerland. The review addresses circadian rhythms, fundamental biological processes governing the 24-hour cycle in living organisms, and their impact on human cognitive and brain functions. It explores how circadian rhythms regulate sleep/wake cycles and cognitive performance, depending on factors like sleep debt and cognitive domain. The review also highlights the consequences of circadian disruption, particularly its link to mental and neurological disorders. Annu Rev Psychol. epub dec 24. doi: 10.1146/annurev-psych-022824-043825. p LINKS | News GIGA | Publication on ORBI | Christina Schmidt
2025 GIGA Annual Report | 29 ALL THE PUBLICATIONS GIGA published 522 publications in 2024. You can find all these publications on the GIGA website or in ORBI, the ULiège repository : https://orbi.uliege.be
30 | 2025 GIGA Annual Report Anneline Pinson HER PROJECT Involvement of GnRH in alterations in neocortex development induced by exposure to endocrine disruptors We are all exposed to a growing number of endocrine disruptors. These endocrine disruptors have harmful effects on our health and represent a major public health problem. At the same time, we are facing a drastic increase in the incidence of cognitive and behavioral diseases such as autism spectrum disorders, attention deficit/hyperactivity disorder or anxiety, which cannot be explained by genetic factors alone. It has therefore been proposed that environmental factors, which affect essential developmental processes, are risk factors for neurodevelopmental diseases. My team will therefore aim to determine whether developmental exposure to endocrine disruptors affects the development and maturation of extra-hypothalamic circuits of the neuroendocrine system, within the neocortex, and alters cognitive functions. ABOUT HER Anneline Pinson obtained a Master’s degree in Biomedical Sciences from the University of Liège in 2012. She then completed her doctoral thesis in the laboratory of Prof. Anne-Simone Parent, within the Neuroendocrinology unit of the GIGA. Her research focused on the effects of persistent endocrine disruptors - such as polychlorinated biphenyls - on the hippocampus, a brain region essential for memory. During her doctorate, she spent two research periods in Portland, in the laboratory of Prof. Gary Westbrook, where she learned specialist techniques. After defending her thesis in 2016, Anneline Pinson continued her training in Germany, in Prof. Wieland Huttner’s laboratory at the Max Planck Institute (MPI-CBG) in Dresden. There, she became interested in the development of the neocortex, the largest region of the human brain. In 2023, she returned to Belgium to join Professor Anne-Simone Parent’s laboratory. New Research Associates
2025 GIGA Annual Report | 31 Coraline Radermecker HER PROJECT Study of the long-term effect of pulmonary marginal neutrophils on the identity, dynamics and functions of pulmonary endothelium. The project aims to investigate how pulmonary marginal neutrophils, short-lived immune cells, influence the heterogeneity and function of pulmonary capillary endothelial cells under conditions of homeostasis and during inflammatory processes. This will improve our understanding of endothelial cell dynamics and heterogeneity, as well as the role played by the neutrophil-endothelial cell axis in the lung. Finally, this project could help identify new therapeutic targets for diseases associated with dysfunction of the vascular system. ABOUT HER Coraline Radermecker has a degree in Veterinary Medicine from the University of Liège. After graduating in 2012, she was quickly drawn to the world of research, a passion that came to the fore when she met Professor Fabrice Bureau, a specialist in Cellular and Molecular Immunology. During her studies, although she initially intended to pursue a career in equine medicine, her curiosity for basic sciences such as physiology, biology and immunology led her to explore the field of research. It was during an internship in Professor Bureau’s laboratory that she discovered a real vocation for scientific research. This experience led her to undertake a PhD in Immunology in the same laboratory. After spending four years working on her doctoral thesis, she joined Professor Thomas Marichal’s Immunophysiology laboratory, where she continued her research. In 2024, she was appointed a qualified researcher by the F.R.S.-FNRS to continue her research on pulmonary neutrophils. Throughout her career, Coraline has combined her passion for basic science and applied research, while making a significant contribution to the advancement of knowledge in immunology and physiology.
32 | 2025 GIGA Annual Report H2020 projects 2024 Horizon Europe (2) Cluster 1 - Health MERLON Merging scientific Evidence with Regulatory practices and Leveraging identification Of endocrine disruptors using New approach methodologies p Anne-Simone Parent, Julie Bakker, Charlotte Cornil 798 125 € The MERLON project, coordinated by the Technical University of Denmark, unites 15 partners including GIGA in an international consortium addressing endocrine disrupting chemicals (EDCs), a rising health concern linked to hormone-related disorders. MERLON aims to improve identification of EDCs by integrating multispecies molecular research, new approach methodologies (NAMs), human epidemiology, and systems biology. The focus lies on sexual development stages from fetal differentiation to maturity. By closing knowledge gaps on EDC effects on human health, MERLON supports better regulatory frameworks in the EU and beyond. The consortium involves universities, research institutes, and hospitals across seven European countries. GIGA-Neurosciences contributes to studies on EDC impacts on brain development using in vivo and in vitro models. Funded by the EC’s Horizon 2020 program, MERLON advances safer chemical regulation through innovative science. Horizon Europe - Widening Participation and spreading excellence SYNHEALTH Synergy for Healthy Longevity p Souad Rhamouni 98 750 € Researchers at Genos pioneered highthroughput glycomics 15 years ago, integrating it into major epidemiological and clinical studies. Through participation in EU projects like 3TR and SYSCID, Genos analyzed over 200,000 glycomes and identified promising glycan biomarkers. The SynHealth project aims to valorize these discoveries and prepare them for ERDF funding and exploitation in two Croatian and one Slovenian region, in collaboration with the University of Maribor. Support comes from Horizon partners Karolinska Institute and University of Liège, alongside innovation and technology transfer partners F6S and GlycanAge, the latter commercializing glycan biomarkers in health and wellness. SynHealth will demonstrate adoption of glycan biomarkers for personalized preventive healthcare in real-world settings, paving the way for future clinical diagnostic applications.
2025 GIGA Annual Report | 33 Horizon Europe (1) MSCA - Marie Sklodowska-Curie Actions Staff Exchanges DOC-BOX Development of a multimodal toolbox to ensure a fast and reliable diagnosis of consciousness disorders. p Charlotte Martial 225 400 € DoCBox aims to develop a fast and easy-touse toolbox combining behavioral, neuroimaging, and neurophysiological assessments to accurately diagnose patients with disorders of consciousness (DoC). Designed to meet the strict time constraints of clinical settings, this toolbox will improve evaluation and care for this vulnerable population. The project promotes interdisciplinary research and international collaboration to translate and validate tools such as behavioral scales and software pipelines. Its three main goals are: provide new bedside tools to better detect signs of consciousness; identify reliable neurophysiological and neuroimaging biomarkers and develop user-friendly software; and engage both formal and informal caregivers in diagnosis. With 17 partners across Europe and beyond, the consortium aims to deliver guidelines and policy recommendations to enhance DoC diagnosis and care, advancing understanding of consciousness disorders. Horizon Europe (1) MSCA - Marie Sklodowska-Curie Actions Postdoctoral Fellowships TRIQ Searching for TRans-eQTL affecting the risk to develop Inflammatory Bowel Disease p Souad Rahmouni 191 760 € Inflammatory Bowel Disease, including Crohn’s disease and ulcerative colitis, now afflict close to 1/250 individuals in industrialized societies. There is a pressing need for effective preventive means as well as curative drugs. CiseQTL analyses are uncovering a growing list of genes that are perturbed by IBD risk variants detected by GWAS, constituting a list of prime drug targets for the pharmaceutical industry. Cis-eQTL effects trigger downstream effects – both within the same (intracellular) and other cell types(intercellular) – that culminate in disease declaration. Some of these downstream effects are accompanied by changes in transcriptlevels referred to as trans-eQTL effects. The aim of the TRIQ project is to take advantage of the CEDAR-II dataset – transcriptomedata for up to 400 individuals in > 75 IBD-relevant cell types – to identify trans-eQTL effects that mediate IBD predisposition. The genes that are perturbed by these trans-effect will include druggable targets that constitute prime targets for the development of new IBD therapies. Horizon Europe (1) MSCA - Marie Sklodowska-Curie Actions Postdoctoral Fellowships DENOVO Towards an Integrative Model of the Relationship Between Episodic Memory and Novelty Detection Through a Behavioural and Neuropsychological Approach p Christine Bastin 139 270 € DENOVO explores how different types of novelty—absolute (entirely new), contextual (familiar in a new context), and associative (new combinations of known elements)—interact with episodic memory. While novelty is known to support memory encoding, their precise relationship remains unclear. Unlike previous research based mainly on neuroimaging, DENOVO combines behavioral testing, cognitive psychology, and neuropsychology of aging. The project examines whether absolute novelty is directly linked to memory, while the other types may act more independently. Findings could improve understanding of memory mechanisms and inform the diagnosis and management of conditions like amnestic Mild Cognitive Impairment and Alzheimer’s disease.
34 | 2025 GIGA Annual Report WEL Research Institute projects 2024 Alain Chariot Laboratory of Medical Chemistry Translational reprogramming helps cancer cells to support cell survival and proliferation. This process is regulated by tRNA modifications. Many diseases are characterized by a deregulated translational reprogramming. The tRNA-modifying enzyme is acting as an oncogenic protein in the intestine and in the mammary gland. We recently showed that Elp3 deficiency in hepatocytes leads to lethality post-birth due to lower glucose levels. We will explore how Elp3 promotes cell differentiation in the liver and we will define new Elp3 targets involved in gluconeogenesis. Elp3 deficiency in adipocytes potentiates the gain of weight in mice subjected to a high fat diet. We will identify new actors involved in adipocyte hypertrophy whose mRNA translation is regulated by Elp3. We will also explore whether and how the loss of Elp3 in adipocytes sensitizes mice to obesity-driven liver cancer. Finally, we will address the role of the prolylhydroxylase Lepre-1, a candidate whose expression is regulated by Elp3, in tumor initiation and progression up to metastasis in the intestine. Collectively, our project will shed new lights into mechanisms through which some tRNA modifications are involved in the biology of both hepatocytes and adipocytes with important consequences in hepatic metabolism, obesity and obesity-driven liver cancer. We will also establish the landscape of proline hydroxylation during tumor development in the intestine. ALAIN CHARIOT TRANSLATIONAL REPROGRAMMING THROUGH tRNA MODIFICATIONS IN HEALTH AND DISEASES
2025 GIGA Annual Report | 35 Grégory Ehx Laboratory of Hematology Acute myeloid leukemia (AML) is the most frequent and lethal leukemia among adults. Although chemotherapy results in high rates of remission, most patients relapse, leading to average survival rates of ~10-40%. Relapse is notably mediated by leukemic cells (persisters) surviving chemotherapy, and remaining dormant throughout the remission phase. Because these cells are vastly outnumbered by T cells (the effectors of antileukemic immunity) during remission, targeting them with immunotherapies is a golden opportunity to prevent AML relapse. However, blasts can escape immune recognition through various mechanisms, notably through the expression of immune checkpoint molecules (ICMs). Therefore, our study aims to design immunotherapies targeting persisters by stimulating their T-cell recognition through vaccination and by inhibiting the ICMs protecting them. Recently, we designed a proteogenomic method enabling the detection of MHC-I-presented antigens specifically expressed by AML blasts (TSA) which could serve as vaccination targets. Here, we will use this approach to identify the TSAs presented by persisters generated by treating patient-derived AML cells with chemotherapy. To identify key ICMs protecting persisters, we will perform a large-scale molecular screening in vitro, and more detailed analyses in immunodeficient mice co-transplanted with primary AML blasts and T cells, or without T cells. Through singlecell RNA sequencing, we will track persisters in the bone marrow of AML patients and characterize the evolution of their ICM+TSA expression profile to prioritize the most desirable immunotherapeutic targets. Finally, we will test our immunotherapeutic strategy in a preclinical model of AML in humanized mice. Our study could help prevent AML relapse and could elucidate the immune escape mechanisms of AML cells following chemotherapy. GRÉGORY EHX IMMUNOERADICATION OF PERSISTER CELLS IN AML
36 | 2025 GIGA Annual Report TELEVIE projects 2024 Hematopoietic stem cell transplantation in children with malignant or nonmalignant disorders BARON Frédéric, BRICHARD Bénédicte, SMEESTERS Pierre Impact of methylglyoxal stress in cancer cells: characterization of glycation proteome BELLAHCÈNE Akeila Characterization of glycation stress in glioblastoma as a potential therapeutic target BELLAHCÈNE Akeila Translational reprogramming through tRNA modifications in liver cancer CHARIOT Alain Mechanisms linking a reprogramming of mRNA translation and proinvasive capacities to whole genome doubled cells in Triple Negative Breast Cancers CLOSE Pierre, JÉRUSALEM Guy Targeting Ewing-Sarcoma 3D-Chromatin architecture regulators as a new anti-cancer strategy DEQUIEDT Franck In-depth characterization of the tumor antigen landscape to prioritize actionable immunotherapeutic targets EHX Grégory Tailoring 3D bone-like models to characterize human coagulant circulating tumor cells GILLES Christine, JÉRUSALEM Guy, GERIS Liesbet Characterization of the anti-tumor properties of extracellular vesicles secreted from OPA1 (Opticatrophy protein 1) knock out cells HERKENNE Stéphanie Chemotherapy Impact and Protection: Preserving Ovarian Function and Fertility MUNAUT Carine, DOLMANS Marie-Madeleine, DEMEESTERE Isabelle Fibroblasts in tumor draining lymph nodes at premetastatic and metastatic stages NOËL Agnès Identifying targetable metabolic adaptations in drug tolerant BRAFV600E mutant lung Adenocarcinoma NOKIN Marie-Julie Targeting fatty acid metabolism to sensitize metastatic ovarian cancer to targeted therapy SOUNNI Nor Eddine Online Resilience Group-Based Training Program, Ecologically Boosted and Scheduled in the Early Cancer Treatment Period of AYAs with Cancer: a Longitudinal Multicenter Randomized Controlled Trial MERCKAERT Isabelle, VAN GESTEL Dirk, LIBERT Yves, LAHAYE Magali, VAN DAMME An, GREGOIRE Charlotte, JÉRUSALEM Guy, DEVALCK Christine, POIRÉ Xavier, DRESSE Marie-Françoise
2025 GIGA Annual Report | 37 TÉLÉVIE PLURI-UNIVERSITY RESEARCH PROGRAMS Intestinal cancers, tumor micro-environment and microbiota CHARIOT Alain, LETELLIER-LAMBERTY Elisabeth tRNAs Modifications and Translational Reprogramming in Leukemias-Associated Treg CLOSE Pierre, PAGGETTI Jérôme Metabolic Modulation for Enhanced Anticancer Immunity FERON Olivier, HERFS Michael Viral cancer models and single-cell genomics to study tumor evolution: retrospective tracing of a novel catalogue of tumor-specific somatic alterations in the rare tumor ancestor cell GEORGES Michel, CHARLIER Carole, JESCHKE Jana, VAN DEN BROEKE Anne Investigating formate-induced reprogramming of mRNA translation in lung cancer MEISER Johannes, BLOMME Arnaud PROJECTS RENEWAL Systems biology approaches for comprehensive analyses of immune response to BNT162b2 mRNA and inactivated influenza vaccines in allogeneic hematopoietic stem cell transplant recipients BARON Frédéric Impact of ozone exposure on pulmonary microenvironment and metastatic dissemination CATALDO Didier Importance of transfer RNA editing in colon cancer CLOSE Pierre Characterization of a novel role for FET oncogenic fusions in the regulation of mRNA stability DEQUIEDT Franck Discovery and targeting of tumor-specific antigens presented by diapaused acute myeloid leukemia cells EHX Grégory Inhibition of “second- generation” B7-H3 and CD112 immune checkpoints for the treatment of malignant pleural mesothelioma HERFS Michaël Identification of inhibitors of G proteincoupled receptors to protect against cisplatin-induced ototoxicity MALGRANGE Brigitte Impact of ovarian tissue preservation on future fertility in young cancer patients according to age and chemotherapy dose MUNAUT Carine VE-Cadherin dynamics and interactomics in tumoral lymphangiogenesis NOEL Agnes Study of PTK7 expression and roles in glioblastoma and targeting approaches ROGISTER Bernard Characterization of CXCR4 and ACKR3 receptors in glioblastoma tumor microenvironment ROGISTER Bernard Insights into the role of microRNA-encapsulated endothelial extracellular vesicles in pre-metastatic niche formation and metastasis in breast cancer STRUMAN Ingrid Eosinophils inhibit response to chemotherapy: mechanisms and preclinical investigation in mesothelioma WILLEMS Luc
38 | 2025 GIGA Annual Report Léon Fredericq Foundation The “Fondation Léon Fredericq” - created by the CHU de Liège, the Université de Liège, the Fonds Léon Fredericq ASBL and the Centre Anticancéreux ASBL - aims to strengthen support for fundamental, clinical and translational research, to mobilize against cancer and to support innovative projects carried out by the CHU and the Université de Liège for the benefit of patients. This is an essential project within a Faculty of Medicine and a university hospital with almost 800 researchers and over 50 medical departments, each working to improve patient care. In 2024, the Léon Fredericq Foundation provided almost 2.5 million euros in support of medical and biomedical research in Liège, awarding 196 grants to researchers and doctors at the University Hospital and the University of Liège, including 135 grants to GIGA researchers. A much-needed boost for young researchers in constant need of additional funding. Convinced of its raison d’être, the Léon Fredericq Foundation has always supported the GIGA with ardour and determination. To this end, it funds the work of its researchers through operating grants, their training through doctoral grants, their scientific development through travel grants, their collaboration with the CHU de Liège through the allocation of clinician-researcher mandates and subsidies for translational projects, and their use of technological platforms. By supporting the GIGA, the Léon Fredericq Foundation promotes the acquisition of new knowledge, scientific excellence and innovation, all in the service of patients. Values it holds dear. It also encourages multidisciplinary projects. It also favours the acquisition and implementation of the most advanced technological resources in the service of daring research. Last but not least, the foundation relies on the creativity of our young researchers, giving them the means to serve medical progress and meet the medical challenges of today and tomorrow. Since its inception, the Foundation has shared the GIGA’s challenges and perspectives, and is keen to contribute to its success. However, nothing would be possible on its own. That’s why, over the course of its history, the Léon Fredericq Foundation has become intimately involved in the life of the Cité Ardente. In this way, it has succeeded in forging privileged links with its environment and gaining the support of numerous citizens and partners who, over the years, have shared the essence of its missions and its enthusiasm. On behalf of the GIGA researchers and the Léon Fredericq Foundation, I would like to take this opportunity to extend my heartfelt thanks to each and every one of these invaluable supporters for their generosity, commitment and invaluable trust. Caroline Mazy, Director of the Fondation Léon Fredericq
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