Jean-Louis Gueant Nutrition-Genetics-Environmental Risks

Course and current status

Jean-Louis Guéant, MD, DSc, is Professor of Medical Biochemistry-Molecular Biology at the University of Lorraine, Faculty of Medicine, Director of UMR-S Inserm 1256, Head of the Department of Biochemistry-Molecular Biology-Nutrition at the University Hospital of Nancy. He followed a MD, PhD double cursus at the Faculty of Medicine and the Faculty of Sciences of the University Henri Poincaré of Nancy, with the qualification in Hepato-Gastroenterology in 1984, and the degree of Doctor of Science in Nutrition in 1986. He is recruited as Master of Conferences - Hospitaller Practitioner in 1987 and appointed Professor of Universities - Hospital Practitioner in 1990. Prior to this appointment, he made several post doc stays at the State University of New York and the Institute Minerva of Helsinki (with R Gräsbeck as mentor). He then directs one of the 3 research teams of Inserm Unit 308 (director JP Nicolas) from 1988 and obtains the creation of an EP-CNRS team in 1996, which will become EMI-Inserm in 1999, then UMR-S Inserm 724 in 2002, UMR_S Inserm 954 in 2009 and UMR_S Inserm 1256. This Inserm Unit brings together nearly 70 people, including 3 Inserm researchers and 36 academic investigators in experimental and clinical research, around a research project on the interactions between nutrition, genes and the environment. In this context, he has been principal investigator of many national contracts. In hospital, he has contributed to the creation of the Reference Center for Rare Diseases of Metabolism in which he carries out a very specialized medical consultation on rare metabolic diseases with a regional, national and international recruitments of patients.

Current academic positions: president of the 44th section of the French national university committee (CNU: medical biochemistry and molecular biology, physiology, cell biology and nutrition), president of the National Committee of Medical Biology. corresponding member of the French National Academy of Medicine. Past-academic positions. Deputy Dean for scientific affairs of the Faculty of Medicine of Lorraine University, deputy president of the INSERM scientific committee for cardiovascular diseases/diabetology/nutrition (2008-2012), member of the national scientific council of INSERM (2012-end of 2016), president of the French national college of Medical Biochemistry and Molecular Biology (2010-2016).

Current management/coordination of grants and networks: coordinator of FHU ARRIMAGE (collaborative network between local Inserm units and clinical research of the University Regional Hospital Center of Nancy) and the “contrat de programme Etat Région Lorraine” (CPER) “Sciences et technologies pour la Santé” (STS) (2015-2018), PI PHRC « PANGENOMIC-BL » (2013-2015). Coordination of international network/Task force ENDA-EAACI on pharmacogenetics of drug reactions.

Editorial and peer review activity. Member of the editorial board of Human Genetics (2016), guest editor of Biochimie (2014 and 2016). Peer review activity: New Engl J Med, Cell Metabolism, Gastroenterology, Gut, J Hepatology, Hepatology, Circulation, Am J Clin Nutr, Scientific Reports, J Nutr, Br J Nutr, Nutrients, FASEB J, Mol Psychiatry, Biol  Psychiatry, JACI, Eur J Clin Nutrition, Arch. Biophys. Biochem., J Med Genet,  Human Mutation, Pharmacogenomics, Pharmacogenomics J, Clinical Experimental Allergy, Allergy, Journal of Chromatography, Biophysica Biochimica Acta, J Thromb. Hemost., Thromb. Hemost, Pediatric Research, Br J Haematology, etc..

Awards: "Elise Cailleret" prize of the National Academy of Medicine, 1981, "Distinguish Scientist Award" of the Sigrid Juselius Foundation of Finland, 1987, honorary member of the Medical Society of Finland, 1989, AGAF award of the American Gastroenterological Association, 2007 and élection membre correspondant Académie Nationale de Médecine, 2014.

Scientific summary

The area of expertise of JL Guéant is focused on the one carbon metabolism and its association with patho-mechanisms of complex metabolic diseases and inherited disorders of cobalamin and folate metabolism. He is also a well-recognized expert in genetic predictors of adverse drug reactions and he made significant contributions in clinical and experimental research of digestive diseases.

His main contributions in the field have been: - The mechanisms of the intraluminal digestive transport of vitamin B12, including the physicochemical and functional  characterization of binding proteins and receptors, the princeps evidence of enterohepatic circulation of cobalamin (Lancet 1986, Gastroenterology, 1991) - the identification of new genetic variants of the one carbon metabolism and their associations with diseases (Blood, 2001, Am J Clin Nutr 2002, 2006, 2012, 2017, J Med Genet 2016) - the  molecular, cellular and tissue consequences of methyl donor deficiency in early life and during aging, related to foetal programming and the consequences on central obesity through epigenomic dysregulations in liver, gut and heart (PNAS 2009a and 2009b, J Pathol 2011, J Hepatol 2008, 2012, Trends End Metab 2014, FASEB J 2012, 2013, 2015, 2016, Gut 2016) – pathomechanisms of digestive and cellular rare diseases of the one carbon metabolism,  with the demonstration that Immerslund-Grasbeck disease results from the impaired expression of intrinsic factor receptor in gut and kidney and the interaction between intracellular transporters and target enzymes in cellular inherited diseases (Gastroenterology 1995, Gastroenterology, 1999, Hum Mol Genet 2013) and the princeps observation of the involvement of epimutations/gene trios in inherited metabolic diseases  (Nature Communications, 2018) – the characterization and mechanisms of immediate drug reactions and crossreactivity (Lancet 1988, 1990, 1992, Ann Intern Med, 2004, New Engl J Med, 2006, Ann Intern Med, 2007), including the influence of environmental and genetic determinants-GWAS (J Allergy Clin Immunol 2013, 2015).

The current research project of the team of JL Guéant is focused on nutrigenomic and epigenomic mechanisms of diseases, with particular interest, but not exclusively, to mechanisms linked to the one-carbon metabolism. It is based on a transversal approach, including cellular and molecular aspects, integrated analysis in animal models and validation of mechanistic hypothesis in population studies. Our project assesses the long-term consequences of dysregulation during gestational period triggered by the environment and later exposures such as overnutrition. The mechanisms that are scrutinized are linked to developmental abnormalities, cellular stress and inflammation and metabolic interactions related to complex diseases and rare metabolism diseases.

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