Jérémie Gautheron
CRCN Inserm HDR, Team Leader at Centre de Recherche Saint-Antoine – UMR 938 Biliary and Fatty Liver Diseases
Awards / Distinctions
- 2021 Winner of the G. & JL. Smadja Award, Société Francophone du Diabète (SFD)
- 2018 Winner of the Émergences program from the Paris City Hall
- 2017 Winner of the FRM return assistance program
- 2015 and 2017 Best Paper Award – RWTH Aachen University
- 2008-2011 MESR grant
Training
My academic career has been marked by a coherent progression in the field of Cellular and Molecular Biology, starting with a Licence at the Université Picardie Jules Vernes, followed by a Master 2 at the UPMC in Cellular and Molecular Biology (BMC).
After passing the doctoral school entrance exam (2008), I began my thesis at Necker Hospital, Université Paris 5, in Prof. Arnold Munnich’s team and under the supervision of Dr. Gilles Courtois, my mentor (2008-2011). During this period, I focused my research on ubiquitination processes in the NF-kappaB signaling pathway, and their dysfunctions associated with various genetic pathologies.
After obtaining my PhD, I spent a long post-doctoral period in Germany in Prof. Tom Luedde’s team (2011-2017). There, I explored programmed cell death processes, using murine cell lines in particular, in the context of various liver pathologies ranging from MASLD to HCC.
My work has demonstrated the key role of necroptosis, a necrosis-like programmed cell death pathway, in the progression of MASLD to steatohepatitis. Ten years ago, our publications in EMBO Mol Med and Nat Commun challenged the predominant perception of apoptosis as the main driver of disease progression. At that time, we hypothesized that blocking apoptosis could lead to a redirection towards necroptosis, a hypothesis confirmed by the deterioration in biological parameters of MASH patients treated with pan-caspase inhibitors in a recent clinical trial.
In August 2017, I returned to France to head up a research group in Pr Chantal Housset’s team. Our research brought new perspectives by demonstrating that the use of specific necroptosis inhibitors offers protection not only against the development of steatohepatitis, but also exerts unexpected effects on the development of steatosis and obesity. These results, rapidly corroborated by other groups after our publication in J Hepatol, have aroused significant interest in the scientific community. These discoveries led to the filing of a patent for the use of necroptosis inhibitors in the treatment of MASLD, currently undergoing maturation at Satt Lutech. We have also developed a new line of research targeting interactions between the liver and adipose tissue in lipodystrophic syndromes (LS). These studies, in collaboration with Prof. Bruno Fève’s team, have recently been published in eLife, BMC Med and Nat Genet.
I took over as co-director of the team in 2022, before assuming full management in September 2023.
Research project
Among digestive diseases, chronic liver disease has a considerable socio-economic impact. They are characterized by a continuous process of inflammation, destruction and regeneration of liver cells, culminating in fibrosis, cirrhosis and ultimately liver cancer.
Cell death of liver parenchymal cells and associated inflammatory responses are present in almost all types of chronic liver disease and represent the initial processes of hepatic fibrosis.
Persistent cell death of liver parenchymal cells initiates a sequence involving the release of damage-associated molecular patterns (DAMPs) from dying cells, triggering inflammation and activation of non-parenchymal liver cells, including myofibroblasts, which will lead to fibrogenesis. Our research projects aim to decipher the cellular and molecular mechanisms underlying the pathogenesis of liver fibrosis, from its initial mechanisms (i.e. inherited molecular defects or cell death) to its ultimate consequence (i.e. liver cancer).
Our research projects combine human studies, the use of mouse models of chronic liver disease, and cellular and molecular biology to achieve our main objective: translating basic research discoveries into therapeutic applications. By adopting a multidisciplinary approach, our aim is to identify new molecular targets for therapeutic intervention to contribute to the development of treatments for these chronic diseases.
“To improve is to change; to be perfect is to change often” Winston Churchill
In the context of a research career, this quote underlines the importance of adaptability and evolution. To progress in scientific research, you need to be open to change and innovation. Discoveries and advances in a particular field often require us to question existing approaches and explore new ideas. She emphasizes that perfection is a dynamic, evolving process. Achieving perfection, in the context of scientific research, means being prepared to constantly modify and refine one’s methods and approaches. It is through self-imposed change and continuous striving for innovation that we can aspire to achieve higher levels of excellence and success.
Publications
- Identification of a new NEMO/TRAF6 interface affected in incontinentia pigmenti pathology. Gautheron J, Pescatore A, Fusco F, Esposito E, Yamaoka S, Agou F, Ursini MV, Courtois G. Hum Mol Genet. 2010 Aug 15;19(16):3138-49. doi: 10.1093/hmg/ddq222. Epub 2010 Jun 7. (P)
- A positive feedback loop between RIP3 and JNK controls non-alcoholic steatohepatitis. Gautheron J, Vucur M, Reisinger F, Cardenas DV, Roderburg C, Koppe C, Kreggenwinkel K, Schneider AT, Bartneck M, Neumann UP, Canbay A, Reeves HL, Luedde M, Tacke F, Trautwein C, Heikenwalder M, Luedde T. EMBO Mol Med. 2014 Aug;6(8):1062-74. doi: 10.15252/emmm.201403856. (P)
- The necroptosis-inducing kinase RIPK3 dampens adipose tissue inflammation and glucose intolerance. Gautheron J, Vucur M, Schneider AT, Severi I, Roderburg C, Roy S, Bartneck M, Schrammen P, Diaz MB, Ehling J, Gremse F, Heymann F, Koppe C, Lammers T, Kiessling F, Van Best N, Pabst O, Courtois G, Linkermann A, Krautwald S, Neumann UP, Tacke F, Trautwein C, Green DR, Longerich T, Frey N, Luedde M, Bluher M, Herzig S, Heikenwalder M, Luedde T. Nat Commun. 2016 Jun 21;7:11869. doi: 10.1038/ncomms11869. (P)
- RIPK1 Suppresses a TRAF2-Dependent Pathway to Liver Cancer. Schneider AT*, Gautheron J*, Feoktistova M, Roderburg C, Loosen SH, Roy S, Benz F, Schemmer P, Büchler MW, Nachbur U, Neumann UP, Tolba R, Luedde M, Zucman-Rossi J, Panayotova-Dimitrova D, Leverkus M, Preisinger C, Tacke F, Trautwein C, Longerich T, Vucur M, Luedde T. *Shared co-first authorship. Cancer Cell. 2017 Jan 9;31(1):94-109. doi: 10.1016/j.ccell.2016.11.009. Epub 2016 Dec 22. (P)
- Inhibition of receptor-interacting protein kinase 1 improves experimental non-alcoholic fatty liver disease. Majdi A, Aoudjehane L, Ratziu V, Islam T, Afonso MB, Conti F, Mestiri T, Lagouge M, Foufelle F, Ballenghien F, Ledent T, Moldes M, Cadoret A, Fouassier L, Delaunay JL, Aït-Slimane T, Courtois G, Fève B, Scatton O, Prip-Buus C, Rodrigues CMP, Housset C, Gautheron J. J Hepatol. 2020 Apr;72(4):627-635. doi: 10.1016/j.jhep.2019.11.008. Epub 2019 Nov 21. (DC)
- EPHX1 mutations cause a lipoatrophic diabetes syndrome due to impaired epoxide hydrolysis and increased cellular senescence. Gautheron J, Morisseau C, Chung WK, Zammouri J, Auclair M, Baujat G, Capel E, Moulin C, Wang Y, Yang J, Hammock BD, Cerame B, Phan F, Fève B, Vigouroux C, Andreelli F, Jeru I. Elife. 2021 Aug 3;10:e68445. doi: 10.7554/eLife.68445. (PC)
- Loss of phospholipase PLAAT3 causes a mixed lipodystrophic and neurological syndrome due to impaired PPARγ signaling. Schuermans N*, El Chehadeh S*, Hemelsoet D*, Gautheron J*, Vantyghem MC, Nouioua S, Tazir M, Vigouroux C, Auclair M, Bogaert E, Dufour S, Okawa F, Hilbert P, Van Doninck N, Taquet MC, Rosseel T, De Clercq G, Debackere E, Van Haverbeke C, Cherif FR, Urtizberea JA, Chanson JB, Funalot B, Authier FJ, Kaya S, Terryn W, Callens S, Depypere B, Van Dorpe J; Program for Undiagnosed Diseases (UD-PrOZA); Poppe B, Impens F, Mizushima N, Depienne C, Jéru I, Dermaut B. *Shared co-first authorship. Nat Genet. 2023 Nov;55(11):1929-1940. doi: 10.1038/s41588-023-01535-3. Epub 2023 Nov 2. (P). News & Views in Nat Rev Endocrinol 2024. doi: 10.1038/s41574-023-00950-0.
