Team leader

Presentation

Our team studies the mechanisms underlying chronic liver disease progression to cirrhosis and its complications, with an emphasis on the identification of prognosis markers and therapeutic targets for fatty liver diseases.Our research program focuses on the identification of immunometabolic targets and biomarkers of liver and systemic inflammation.

Non-alcoholic and alcoholic fatty liver diseases (NAFLD, ALD) are leading causes of liver diseases worldwide. They share common pathogenic features including steatosis and steatohepatitis (alcoholic-ASH and non-alcoholic-NASH) that lead to fibrosis and cirrhosis. Persistent inflammation is a driving force of liver fibrosis progression during NAFLD and ALD. Among patients with cirrhosis, excessive inflammation results in the development of multiorgan failure (defining acute-on-chronic liver failure, ACLF), which often leads to death. The lack of treatment highlights the urgent need for new prognosis markers and specific therapeutic targets that could limit liver injury, fibrosis, progression of cirrhosis to ACLF, and favour liver regeneration.

Ongoing studies include:

  1. The mechanisms underlying monocyte/macrophage reprogramming and the impact on fatty liver disease progression to fibrosis, and on liver regeneration. We target specific pathways we recently uncovered, including canonical and non canonical autophagy, macrophage apoptosis and lipid metabolic targets such as monoacylglycerol lipase (Louvet, Hepatology 2011 ; Mallat, J Hepatol 2013 ; Mallat Am J Physiol 2013 ; Wan Hepatology 2014 ; Gandoura J Hepatol 2015 ; Lodder Autophagy 2015 ; Denaes, 2016, Sci Rep ; Gual, 2017 Am J Physiol ;  Weiss, J Hepatol 2017 ; Habib Gut 2018 ;  Tardelli, Hepatology 2019 ; Tardelli, J Lipid Res 2019 ; Allaire, J Hepatol 2019).
  2. The role of adaptive immune cells (Th17) and non conventional T lymphocytes, in particular Mucosal-associated invariant T (MAIT) cells, in the control of inflammation at sequential steps of fatty liver progression (Guillot, Hepatology 2014 ; Hegde Nat Com 2018 ; Toubal Nat Rev Immunol 2019).
  3. Novel biomarkers, targets and clinical studies evaluating new therapeutic strategies in NAFLD, cirrhosis and ACLF, a syndrome we characterized and in which systemic inflammation is a major trigger (Moreau, Gastroenterology 2013,Gustot Hepatology 2016, Claria J Hepatol 2016, Claria Hepatology 2018, Fernandez, Gastroenterology 2019).
  4. The RHU QUID-NASH projecs, led by Pr Dominique Valla, aims to develop a virtual biopsy for diabetic patients with non-alcoholic fatty liver disease, and to improve the development of new treatments. The project will combine radiomic, métabolomic, transcriptomic and genomic data.

Networks : In addition to RHU QUID-NASH, our group is a founding team of the European Consortium for the Study of Chronic Liver Failure (EF-CLIF) and the French-Indian network (LIA) and Labex Inflamex.

Funding: Inserm, Université Paris-Diderot, Laboratory of Excellence Inflamex, National research agency (ANR), Fondation pour la Recherche médicale (FRM), french associations for the study of the liver and for digestive diseases (AFEF, SNFGE), RHU QUID-NASH Inserm-Transfert, Assistance Publique Hopitaux de Paris (PHRC),