Three researchers honored by the Belgian Royal Academy of Medicine
Marie-Julie Nokin (GIGA Cancer - Laboratory of Biology of Tumor and Development), Justine Huart (GIGA Metabolism & Cardiovascular Biology - Laboratory of Translational Research in Nephrology and CHU - Nephrology) and Grégory Ehx (GIGA Immunobiology - Laboratory of Hematology) were honored for their work at the Royal Academy of Medicine awards ceremony this weekend.
Marie-Julie NOKIN - Henri Fauconnier and Jeanne et Marie François Prizes
Identification of acquired vulnerabilities in the development of resistance to targeted therapies in lung adenocarcinoma
Marie-Julie Nokin holds a PhD in Biomedical and Pharmaceutical Sciences from the University of Liège, and is a Senior Assistant at the Laboratory of Tumor and Developmental Biology (GIGA-Cancer, ULiège), where she heads the "Resistance and vulnerabilities in lung cancer" research group. Her work on the mechanisms of resistance to targeted therapies in lung adenocarcinoma has just been awarded the Henri Fauconnier and Jeanne et Marie François Prizes.
Her research focused on two mutations frequently encountered in lung cancer: KRASG12C and BRAFV600E. In the first case, she has shown that resistance to inactive KRAS inhibitors, such as sotorasib, can emerge without new mutation, but via cellular adaptation leading to increased KRAS activation. By testing an inhibitor specifically targeting active KRAS (RMC-4998), his team has obtained promising results. In the case of BRAFV600E adenocarcinoma, treated with the combination dabrafenib/trametinib, they demonstrated two phases of resistance: a transient state of tolerance exploitable by induction of ferroptosis, followed by genetic resistance in which cells become sensitive to oxidative stress caused by HDAC inhibitors. This work, published in Nature Communications and Cell Reports Medicine in 2024, paves the way for new combinatorial strategies to prolong the clinical efficacy of targeted therapies and develop personalized approaches.
Justine HUART - Médaille du Prix Alvarenga de Piauhy 2024
Exploring the impact of gut microbiota and fecal short-chain fatty acids on blood pressure homeostasis
Justine Huart is a researcher at ULiège's Laboratoire de Recherche Translationnelle en Néphrologie and a nephrologist at Liège University Hospital. Her work on the link between microbiota and blood pressure, carried out as part of her doctoral thesis, has just been awarded the Prix Alvarenga de Piauhy medal.
Essential hypertension is a major cardiovascular risk factor whose pathophysiological mechanisms remain largely unknown. Various studies suggest the involvement of intestinal microbiota (IM) and fecal metabolites in blood pressure (BP) homeostasis. In a first study, we confirmed this association between BP levels and (i) the composition of the MI and (ii) the fecal content of metabolites derived from it in a cohort of 54 men subjected to 24-hour ambulatory BP measurement and stool collection. Stools were analyzed using 16S amplicon sequencing and nuclear magnetic resonance analysis of the fecal metabolome. A significant correlation between different bacteria belonging to the order Clostridiales and AP levels was demonstrated. A good correlation was also found between these AP levels and the entire fecal metabolome. More specifically, higher levels of the three main short-chain fatty acids (SCFAs) (i.e. acetate, butyrate and propionate) were measured in the stools of hypertensive patients (HT) compared with normotensive controls (NT). These SCFAs are produced by the MI in the digestive tract via fermentation of dietary carbohydrates. We then looked at the nocturnal BP profile. When the reduction is insufficient compared with daytime values, we speak of a "non-dipping" BP profile and refer to these patients as "non-dippers". Non-dippers have an increased cardiovascular risk, irrespective of their BP level. We retrospectively analyzed metabolomic data comparing dippers to non-dippers: a significantly higher level of SCFA in the stool of non-dippers compared to dippers was measured. MI composition did not differ between non-dippers and dippers. In a third study, we looked at the longitudinal aspect of MI composition and its metabolites, analyzing their evolution at 5 years, in parallel with the evolution of BP levels in 16 of our male patients recruited in the first study. Mates/wives were also included in this study (n=10). Good correlations between BP levels and the entire fecal metabolome were confirmed in this "mixed" cohort. The fecal content of SCFAs was also higher in HT and non-dipper patients than in NT and dipper patients, respectively. There was no significant difference in the composition of patients' MI after a 5-year follow-up, despite a change in blood pressure status for some of them. These observations suggest that functional changes, such as the differential production of certain metabolites, are more involved in blood pressure homeostasis than structural changes in the IM.
Grégory EHX - Fondation Bekales Prize (Leukemia)
Identification of targets for the development of AML immunotherapies
A qualified F.R.S.-FNRS researcher and head of the Translational Immunology & Leukemia group in the Hematology Laboratory, Grégory Ehx devotes his research to understanding the interactions between leukemia cells and the immune system. His work on new immunotherapy strategies for acute myeloid leukemia has just been awarded the Bekales Foundation Prize.
Acute myeloid leukemia (AML) is an aggressive form of blood cancer and the most common acute leukemia in adults. The aim of Grégory Ehx's research was to identify peptides specifically presented by the major histocompatibility complex (MHC) of leukemia cells, in order to develop a vaccine against this disease. This work led to the creation of BamQuery, a computerized tool for detecting the most specific tumor peptides. Thanks to an original proteogenomic approach, 58 immunogenic peptides widely shared between patients were identified, mainly from cryptic genomic regions such as introns, endogenous retroelements or non-coding RNAs. The team also showed that the hypomethylating agent azacitidine, used as a treatment for AML, increases the expression of these retroelements but induces autophagy in parallel, thus limiting the presentation of derived peptides. These results suggest that an anti-leukemia vaccine should ideally be combined with autophagy inhibitors to maximize its efficacy. Together, these findings pave the way for a new type of immunotherapy against AML.
