We aim to explore chromatin signaling, how its deregulation can lead to pathological states and could be targeted to treat human diseases.
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Our team explores chromatin signaling pathways and how they are deregulated in human diseases.
We are investigating fundamental aspects of chromatin biology in model organisms and nuclear signaling. Indeed, we leverage a wide range of expertise in epigenomics, molecular and cell biology, biochemistry, structural biology, and bioinformatics.
Our team benefits from the active involvement of several clinicians who participate in national and international medical networks to develop our translational research programs. This allows us to further structure translational research in epigenetics in collaboration with Grenoble Alpes University Hospital (CHUGA).
Grenoble is an international center of excellence for R&D, recognized by Forbes as the 5th most innovative city in the world in 2013.
With 80,000 jobs in R&D (7.1% of the population, ranking n°1 in France), the science community of Grenoble offers the attractions of an exceptionally dense research plateau, together with a unique supportive atmosphere for investment and business development, within an outstanding location at the foot of the French Alps.
Grenoble hosts top class research organizations such as EMBL, CNRS, Inserm, INRIA, INRAE, CEA and IRSTEA. It benefits from an international high-tech cluster on digital and nano technologies, as well as R&D centers of multinational industrial R&D leaders (STMicroelectronics, Schneider Electric, etc).
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Improve clinical care with translational research in epigenetics
Our team explores chromatin signaling pathways and how they are deregulated in human diseases. Specifically, we study how chromatin factors control genome organization, gene expression, and cell identity. These mechanisms are largely conserved throughout evolution, from yeast to humans.
We investigate fundamental aspects of chromatin biology in model organisms and nuclear signaling in two distinct pathological contexts: infectious diseases and hematological cancers. For example, our work has led to demonstrating that a novel epigenetic reader is a potential drug target to treat pathogenic fungal infections. We also study abnormal gene expression in aggressive B-cell lymphomas to identify novel cancer drivers. This approach has revealed new lymphomagenesis pathways, including potential novel predictive biomarkers and targets for epigenetic-based therapies.
We leverage a wide range of expertise in epigenomics, molecular and cell biology, biochemistry, structural biology, and bioinformatics. We also benefit from the active involvement of several clinicians who participate in national and international medical networks to develop our translational research programs.
We are pursuing our fundamental exploration of epigenetic mechanisms in model organisms, notably sexual differentiation in the yeast S. cerevisiae. This work is be also carried out in models of aggressive lymphomas, for which treatment resistance currently remains a real clinical challenge. These two application models are perfectly suited to study the intricate link between epigenetic-mediated control of gene expression and the metabolic state of cells. Our current and future projects will therefore be focused on addressing the cross-talk between metabolism and epigenetics.
In addition, our projects will integrate single cell technologies to better capture epigenetic heterogeneity, notably to detect the emergence of drug-resistant cell populations and their contribution to disease progression. These approaches are being implemented in close connection with clinicians (infectiology / onco-hematology).
We have an optimal configuration to carry out truly operational translational research in epigenetics with both experts in biology, epigenetic signaling and medical care. The team comprises 7 physicians, including S. Carras (PHU), PI in the team, but also deputy director of the CHUGA Clinical Research and Innovation Direction (DRCI), and of the Biological Resources Center (CRB).
This active involvement of hospital staff, as well as the perfect alignment of our research objectives with the CHUGA/HCERES axis “Epigenetic, cancer and infertility” put us in a particularly effective position to conduct genuine translational research. We are also increasingly committed to national actions, through for instance, our involvement in the scientific board of the Lymphoma Study Association (LYSA).
Our team is also promoting the development of the local epigenetics community, especially within the Health Campus.
With Jérôme Govin leading the epigenetics department, we are actively working with our colleagues to further develop this community, boost its research potential and increase its local, national and international visibility through structuring actions, teaching and scientific animations (Meetings “Interface Clinics & Epigenetics”, Grenoble Epigenetics Club, Memorandum of Understanding IAB-EMBL).
This research program focuses on epigenetics and chromatin in yeast spores. Yeast sporulation is a widely established model for studying meiosis. However, post-meiotic events and the final differentiation of spores remain largely unexplored. In particular, spores display a very distinct organization of chromatin, which is highly compacted, but ready to reactivate rapidly when given nutrients. We are exploring how chromatin compaction conditions the gene expression program.
We are particularly interested in the mechanisms by which tumor cells escape the epigenetic controls that govern their somatic identity, enabling them to acquire aberrant identities. In collaboration with the EpiMed platform (IAB), we have adapted a bioinformatics pipeline, which was applied to transcriptomic data from large patient cohorts to identify “off-context” gene expression in lymphoma. This innovative approach has unraveled several aberrant gene reactivations associated with patient prognosis that are being functionally investigated with the objective of identifying novel druggable cell vulnerabilities.
Diffuse large-cell lymphoma (DLBCL) is an aggressive and frequent hematological malignancy. DLBCLs are driven by major epigenetic deregulations, as they harbor many mutations in chromatin factors. DLBCL therefore represents an attractive system to study the link between epigenetic deregulation and therapeutic resistance. We are currently investigating how these alterations shape the epigenetic landscapes and how their heterogeneity conditions the emergence of persistent cell populations using cutting edge single-cell epigenomics. In this objective, we are exploiting various lymphoma models and patient cohorts to reveal novel epigenomic mechanisms of lymphoma progression and resistance.
A first project is developing new molecules capable of acting on infections by pathogenic fungi. These infections kill around 1.6 million people every year, as many as tuberculosis or malaria. The alarming increase in drug-resistant strains, combined with the toxicity, high cost and limited repertoire of available drugs, has created an urgent need for new therapeutic agents.
We collaborated with Carlo Petosa (Structural Biology, IBS) and Charles McKenna (Medicinal Chemistry, USC, Los Angeles, USA), creating the perfect opportunity to transfer our expertise on the Bdf1 protein to biomedical applications. By screening chemical libraries, we have identified small-molecule compounds that inhibit this protein in pathogenic yeasts of the Candida genus. These results could ultimately lead to the development of new classes of antifungal drugs.
We are also interested in how epigenetic inhibitors can be used to treat high-grade B lymphomas. We are particularly interested in bromodomain inhibitors, to better characterize their molecular targets and rationalize their clinical use as single agents or in combination therapies.
Finally, we are studying also the impact of a new generation of bromodomain inhibitors on the inflammatory response. We are evaluating the anti-inflammatory effect of a new generation of BET inhibitors, derived from an innovative synthesis route based on green chemistry (collaboration Yung-Sing Wong, DPM/UGA) in cellular and preclinical models of inflammation (in ovo and in a rat model of inflammation-induced hepatocellular carcinoma, (collaboration T. Decaens / Z. Macek-Jilkova, IAB/CHUGA and Inovotion).
Post Docs and PhD students
Rotation students (2023 – 2024)
We are proud that 100% of our former members have a fulfilling job.
Post Docs & PhD
Former rotation students
The full list of publications can be found here.
Selection of our major papers