CV Science

Alain L. Servin PhD Cell Biology

Course and current status

Date of Birth : 1946, December 11. Paris 14, France

Academic titles :

1973 - Doctorat en Sciences Naturelles. University Paris-Sud 11

1979 - Capacity of Law. University Nanterre Paris 10

1980 - Master of Law Pharmaceutical. University Paris-Sud 11

1987 - Doctorat d’Etat es Sciences (PhD). University Pierre et Marie Curie Paris 6

Positions and Laboratories:

1980-1985 Engineer of research at Inserm (French National Institute of Health and Medical Research). Inserm Research Center. Saint Antoine hospital Paris

1988-1995 Research Unit 178 Inserm « Différenciation et Neuroendocrinologie de Cellules Digestives ». Paul Brousse hospital Villejuif

1994-1998 Head of CJF 94.07 Inserm « Physiopathologie des Microorganismes entérovirulents ». Faculty of Pharmacy Châtenay-Malabry. University Paris-Sud 11

1995 Director of research at Inserm

1999-2005 Head of Research Unit 510 Inserm "Pathogènes et Fonctions des Cellules Epithéliales Polarisées”. Faculty of Pharmacy Châtenay-Malabry.

2002-2005 Head of Institut de Signalisation et d’Innovation Thérapeutique. Faculty of Pharmacy Châtenay-Malabry

2005-2011 Head of Team « Signaling and Pathogen-host cell interaction ». Research Units 756 and 984 Inserm. Faculty of Pharmacy Châtenay-Malabry

2012 UMR 8076 (BioCIS) CNRS et Université Paris-Sud. Team "Thérapeutique Anti-Parasitaire "

Distinctions and Prizes :

French Academy of Medicine (Prix Clarens 1975 and Prix de Pharmacie 1988)

Officier de l’Ordre National du Mérite, 2008

Main recent activities :

Scientific Council Inserm (1995-1999 and 2003-2007)

Specialized Scientific Committees Inserm n° 1 (Microbiology, Genetic, Pharmacology) (1983-1987), n° 2 (Gastroenterology, Nephrology) (1991-1994), and Committee Infectious and Parasitic Diseases in France and Worldwide (1992-1995)

Committee of Human Nutrition. French Agency Afssa « Sécurité Sanitaire des Aliments » ((Afssa) 2006-2012)

2012-... Expert Scientific Committee Human Nutrition. French Agency for Food, Environment and Occupational Health and Safety (Anses)

2012-...Expert consultant and scientific advisor

Consultations and Expert Scientific Committees: Food and Agriculture Organization of the United Nations (FAO/WHO), Grant Commitees NIH, Canadian Institutes of Health; CONICYT; ECOS; Agency for Science; Welcome Trust; European Community; Israel Science Foundation, United States-Israel Binational Science Foundation; International Foundation for Science; Broad Foundation; French National Agency AERES, ANR...

Major publications

Liévin-Le Moal, V., and A.L. Servin. 2014. Anti-infective activities of human intestinal microbiota Lactobacillus strains: from probiotics to gastrointestinal anti-infectious biotherapeutic agents. Clin. Microbiol. Rev. 27:167-199

Liévin-Le Moal, V., and A.L. Servin. 2013. Pathogenesis of enterovirulent bacteria: Lessons from cultured fully differentiated human colon cancer cells. Microbiol. Mol. Biol. Rev. 77:380-439

Liévin-Le Moal, V., R. Amsellem, and A.L. Servin. 2011. Impairment of swimming motility by antidiarrheic Lactobacillus acidophilus Strain LB retards internalization of Salmonella enterica serovar Typhimurium within human enterocyte-like cells. Antimicrobial. Agents Chemother. 55:4810-4820

Liévin-Le Moal, V., Y. Comenge, V. Ruby, R. Amsellem,V. Nicolas, and A.L. Servin. 2011. Secreted autotransporteur toxin (Sat) triggers autophagy in epithelial cells that relies on cell-detachment. Cell. Microbiol. 13:764-785

Liévin-Le Moal, V., I. Beau, C. Rougeaux, I. Kansau, S. Fabrega, C. Brice, N. Korotkova, and A.L Servin. 2011. Apical expression of human full-length hCEACAM1-4L protein renders the Madin-Darby Canine Kidney cells responsive to lipopolysaccharide leading to TLR4-dependent Erk1/2 and p38 MAPK signaling. Cell. Microbiol. 13:775-785

Guignot, J., S. Hudault, I. Kansau, I. Chau and A.L. Servin. 2009. AfaE/DraE adhesin subunits are sufficient to promote DAF and CEACAMs receptor-mediated internalization of Afa/Dr diffusely adhering Escherichia coli into epithelial cells. Infect. Immun. 77:517-531

Rougeaux, C., C.N. Berger, and A.L. Servin, 2008. CEACAM1-4L down-regulates hDAF-associated signaling after being recognized by the Dr adhesin of diffusely adhering Escherichia coli. Cell. Microbiol. 10 :632-654

Beau, I., Cotte-Lafitte, J., Géniteau-Legendre, M., and A.L. Servin. 2007. A NSP4-dependent mechanism by which Rotavirus impairs lactase enzymatic activity in brush border of human enterocyte-like Caco-2 cells. Cell. Microbiol. 9:2254-2265

Beau, I., Berger, A., and Servin, A.L. 2007. Rotavirus impairs the biosynthesis of brush-border-associated dipeptidyl peptidase IV in human enterocyte-like Caco-2/TC7 cells. Cell. Microbiol. 9:779-89

Guignot, G., Chaplais, C., Coconnier-Polter, M.H., and Servin, A.L. 2007. The secreted autotransporteur toxin, Sat, functions as a virulence factor in Afa/Dr diffusely adhering Escherichia coli by promoting lesions in junctional domain of polarized epithelial cells. Cell. Microbiol. 9:204-221

Atassi, F., D. Brassart, P. Grob, F. Graf, and A.L. Servin. 2006. Lactobacillus Strains isolated from the vaginal microflora of healthy women inhibit vaginosis-associated bacteria in co-culture and in cultured cells. FEMS Immunol. Med. Microbiol. 48:424-32

Coconnier-Polter, M. H., V. Lievin-Le Moal, and A. L. Servin. 2005. A Lactobacillus acidophilus strain of human gastrointestinal microbiota origin elicits killing of enterovirulent Salmonella enterica serovar Typhimurium by triggering lethal bacterial membrane damage. Appl Environ Microbiol 71:6115-20

Liévin-Le Moal, V., Servin A.L., and Coconnier-Polter, M.H. 2005. The increase in mucin exocytosis and the upregulation of MUC genes encoding for membrane-bound mucins induced by the thiol-activated exotoxin listeriolysin O is a host cell defense response that inhibits the cell-entry of Listeria monocytogenes. Cell. Microbiol. 7:1035-1048

Martin-Latil, S., J. Cotte-Laffitte, A.M.Marie Quéro, M. Géniteau-Legendre, and A.L. Servin. 2004.^.A cyclic AMP protein kinase A-dependent mechanism by which rotavirus impairs the expression and enzyme activity of brush border-associated sucrase-isomaltase in differentiated intestinal Caco-2 cells. Cell. Microbiol. 8:719-731

Berger, C.N. O. Billker, T. Meyer, A.L. Servin, and I. Kansau. 2004.^.Differential recognition of members of the carcinoembryonic antigen family by Afa/Dr adhesins of diffusely adhering Escherichia coli (Afa/Dr DAEC). Mol. Microbiol. 4:963-983

Liévin-Le Moal, V., R Amsellem, A L Servin, and M-H Coconnier. 2002. A Lactobacillus acidophilus (strain LB) from resident adult human gastrointestinal microflora exerts activity against brush border damages promoted by a diarrheagenic Escherichia coli in human enterocyte-like cells. Gut 50: 803-811

Liévin-Le Moal, V., G. Huet, J.-P. Aubert, J. Bara, M.-E. Forgue-Lafitte, A.L. Servin, and M.-H. Coconnier. 2002. Activation of mucin exocytosis and upregulation of MUC genes in polarized human intestinal mucin-secreting cells by the thiol-activated exotoxin listeriolysin O. Cell. Microbiol. 8:515-529

Peiffer, I., M.-F. Bernet-Camard, M. Rousset, and A.L. Servin. 2001. Impairments in enzyme activity and biosynthesis of brush border-associated hydrolases in human intestinal Caco-2/TC7 cells infected by members of the Afa/Dr family of diffusely-adhering Escherichia coli (DAEC Afa/Dr). Cell. Microbiol. 3:341-357

Liévin, V., I. Peiffer, S. Hudault, F. Rochat, D. Brassart, J.R. Neeser, and A.L. Servin. 2000. Bifidobacterium strains from resident infant human gastrointestinal microflora exert antimicrobial activity. Gut. 47 :646-652

Coconnier, M.H., M. Lorrot, A. Barbat, C. Laboisse, and A.L. Servin. 2000. Listeriolysin O-induced stimulation of mucin exocytosis in polarized intestinal mucin-secreting cells: evidence for toxin recognition of membrane-associated lipids and subsequent toxin internalization through caveola. Cell. Microbiol. 6:487-504.

Guignot, J., I. Peiffer, M.F. Bernet-Camard, D. Lublin, C. Carnoy, S.L. Moseley, and A.L. Servin. 2000. Recruitment of CD55 and CD66e brush border-associated glycosylphosphatidylinositol-anchored proteins by members of the Afa/Dr diffusely-adhering Escherichia coli family infecting the human polarized intestinal Caco-2/TC7. Infect. Immun. 68:3554-3563

Jourdan, N., J.P Brunet, C. Sapin, A. Blais, J. Cotte-Laffitte, F. Forestier, A.M. Quero, G. Trugnan, and A.L. Servin. 1998. Rotavirus infection reduces sucrase-isomaltase expression in human intestinal cells by perturbing protein targeting and organization of microvillar cytoskeleton. J. Virol. 72 :7228-7236

Coconnier, M.H., V. Liévin, M.F. Bernet-Camard, S Hudault., and A.L. Servin 1997. Antibacterial effect of the adhering human Lactobacillus acidophilus strain LB. Antimicrob. Agents Chemother. 41 :1046-1052

Bernet-Camard, M.F., Coconnier, M.H., Hudault, S., and Servin, A.L. 1996. Pathogenicity of the diffusely-adhering C1845 Escherichia coli: F1845 adhesin-decay accelerating factor interaction, brush border microvillus injury and actin disassembly in cultured human intestinal epithelial cells. Infect. Immun. 64 :1818-1928.

Bernet, M.F., Brassart, D, Neeser, J.R. and Servin A.L. 1994. Lactobacillus acidophilus LA 1 binds to cultured human intestinal cell lines and inhibits cell-attachment and cell-invasion by enterovirulent bacteria. Gut 35:483-489.

 Kernéis, S., Bilge, S., Fourel, V., Chauvière, G., Coconnier, M.H. et Servin, A.L. 1991. Use of purified F1845 fimbrial adhesin to study localization and expression of receptors of enteropathogenic Escherichia coli during enterocytic differentiation of human epithelial cell lines, HT-29 and Caco-2 in culture. Infect. Immun. 59:4013-4018

1999 European Patent N° EP1034787A1 - Title: Lactobacillus strains preventing diarrhea caused by pathogenic bacteria.

2002 European Patent N° EP1206523A1 - Title: Lactobacillus strains capable of preventing diarrhoea caused by pathogenic bacteria and rotaviruses.

2004 European Patent N° 03720781.8-2405-IB0301739 - Title: Antibacterial activity by a strain of Lactobacillus fermentum

Scientific summary

Servin’s laboratory in the field called Cellular Microbiology, has focused his research interest on intestinal host cell-microbial pathogen interactions by combining cell biology with microbiology. Research conducted by Alain L. Servin and colleagues for over 20 years focused on understanding the cellular and molecular mechanisms of pathogenesis of enterovirulent or uropathogenic Escherichia coli expressing Afa/Dr adhesins (diffusely-adhering E. coli - DAEC) and rotavirus. The main contributions are:

For Afa/Dr DAEC pathogenesis: (i) demonstration of the high specificity of human infection; (ii) identification of a new family of membrane receptors for Afa/Dr adhesins, the human carcinoembryonic antigen adhesion molecules (hCEACAMs); (iii) demonstration that interaction of Afa/Dr adhesins with hDAF and hCEACAMs activates host cell signaling pathways; (iv) molecular identification of mechanisms leading to disorganization of cell polarization and impairment of intestinal functions; (v) demonstration of proinflammatory responses in human intestinal cells (production of IL-8, TNFα and IL-1β, transmigration and activation of neutrophils, up-regulation of hDAF and intestinal vascular epidermal growth factor (VEGF)); (vi) demonstration that Sat toxin alters junctional domain of intestinal polarized cells, and promotes an autophagy-dependent cell death and epithelial cell detachment; (vii) identification of full-length hCEACAM1-4L protein as a novel LPS-conveying molecule at the mucosal surface for subsequent MD-2/TLR4 receptor-dependent MAPK Erk1/2 and p38 signaling.

For Rotavirus pathogenesis: (i) identification of intracellular calcium for structural alterations in enterocyte; (ii) identification of activated signaling pathways (calcium, cyclic AMP protein kinase A) for rotavirus-induced impairment of synthesis, intracellular transport and activity of intestinal brush border functional proteins (sucrase-isomaltase, dipeptidylpeptidase IV, lactase, glucose and peptides transporters), and structural and functional damages in tight junction.

Basic research is accompanied by translational research such as the development of new human microbiota probiotic Lactobacillus strains used as biotherapeutic agents to treat bacterial and viral diarrhea and vaginal infections.

At Paris-Sud University, 20 pre- and post-doctoral fellows have been mentored who continued theit careers in academia and industry