MENENDEZ, Alfredo, PhD.

Molecular immunology and pathophysiology of hepatobiliary bacterial infections

Associate Professor

Contact

E-mail: Alfredo.Menendez@USherbrooke.ca
Phone : 819 821-8000 ext 75326
Fax: 819 820-6831

Research Rlevance

Inflammatory clinical conditions of the hepatobiliary system are frequent in the general population and are frequently complicated with bacterial infections. They typically result in dramatic biliary and gastrointestinal dysfunction leading to profound alterations in the overall body physiology and immunology. However, for most of these clinical conditions, the etiology and the molecular mechanisms of pathogenesis are still unclear.

The research program of Pr. Menendez targets the triad liver-bacteria-intestines. He is particularly interested in the study of the mechanisms underlying liver and biliary immunopathology in clinical conditions with a potential involvement of bacterial infection.

The gastrointestinal tract is an extremely complex site constantly exposed to pathogenic and commensal bacteria. Given its anatomical and functional connection with the hepatobiliary system, a fundamental aspect of Pr Menendez’s research is the integrated study of multiple aspects of hepatic and intestinal physiology, microbiology and immunology, with a strong emphasis in the reciprocal interactions between the two organ systems. These studies should help to clarify the role of bacteria in hepatobiliary inflammation and pathology and contribute to basic research targeting the immunotherapeutic management of those clinical conditions.

Representative Achievements

  • Discovery Grant to study the impact of biliary function in the intestinal immunological landscape, from: Natural Sciences and Engineering Research Council (2011-2016)
  • Representative publications: I&I 79:1759-1769, 2011; I&I 79:1536-1545, 2011; Nature Immunol. 11:49-50, 2010 (N&V); Mol. Immunol. 47:1137-1148, 2010;  JID 200:1703-1713, 2009; FASEB Journal 22:1380-1392, 2008; Microbes and Infection 10:922-927, 2008; Current Opinion in Immunology 19:385-391, 2007; JMB, 369:696-709, 2007

Know-How & Opportunities for Collaboration

  • In vivo immunopathogenesis of hepatobiliary and gastrointestinal Salmonella in mouse infection models. In vitro systems of cultured cell infections. Gastrointestinal immunology and antimicrobial peptides biology
  • Phage display technology, antibody epitope mapping, protein-protein interactions, vaccine development.

Recent publications

G. Romain, S. Tremblay, E. T. Arena, L. C. M. Antunes, S. Covey, M. T. Chow, B. B. Finlay & Menendez A., Enterohepatic bacterial infections dysregulate the FGF15-FGFR4 endocrine axis. BMC Microbiology 13:238, 2013 (Highly Accessed). PMID: 24165751

Menendez A., Willing BP, Montero M, Wlodarska M, So CC, Bhinder G, Vallance BA & Finlay BB. Bacterial stimulation of the TLR-MyD88 pathway modulates the homeostatic expression of ileal Paneth cells alpha-defensins. Journal of Innate Immunity, 5:39-49, 2013. PMID: 22986642

Arena ET, Auweter SD, Antunes LC, Vogl AW, Han J, Guttman JA, Croxen MA, Menendez A., Covey SD, Borchers CH, Finlay BB. The deubiquitinase activity of the Salmonella Pathogenicity Island 2 effector, SseL, prevents accumulation of cellular lipid droplets. Infection and Immunity 79:4392-4400, 2011.

Antunes LC, Andersen SK, Menendez A., Arena ET, Han J, Ferreira RB, Borchers CH, Finlay BB. Metabolomics r.eveals phospholipids as important nutrient sources during Salmonella growth in bile in vitro and in vivo. Journal of Bacteriology 193(18):4719-4725, 2011.

Wlodarska, M., Willing, B., Keeney, K.M., Menendez A., Bergstrom, K.S., Gill, K., Russell, S.L., Vallance, B.A. and Finlay, B.B. Antibiotic treatment alters the colonic mucus layer and predisposes the host to exacerbated Citrobacter rodentium-induced colitis.  Infection and Immunity 79(4):1536-1545, 2011.

L. Caetano M. Antunes, Ellen T. Arena, Menendez A., Jun Han, Rosana B. R. Ferreira, Michelle M. Buckner, Petra Lolić, Christoph H. Borchers and B. Brett Finlay. The impact of Salmonella infection on host hormone metabolism revealed by metabolomics. Infection and Immunity 79(4):1759-1769, 2011.

Menendez A., Ferreira RB. & Finlay BB. Defensins keep the peace too. Nature Immunology 11:49-50, 2010.

Irving, M.B., Craig, L., Menendez A., van Houten, N.E., Montero, M. and Scott, J.K. Exploring Peptide Mimics for the Production of Antibodies Against Discontinuous Protein Epitopes. Molecular Immunology 47:1137-1148, 2010.

Menendez A., Arena, ET., Guttman, JA., Thorson, L., Vallance, BA., Vogl, W. & Finlay BB. Salmonella infection of gallbladder epithelial cells drives local inflammation and injury in a model of acute typhoid fever. The Journal of Infectious Diseases 200:1703-1713, 2009, (issue cover, highlighted in F1000).

O.L. Champion, Y. Valdez, L. Thorson, J.A. Guttman, Menendez A., E.C. Gaynor & B.B. Finlay. A murine intra peritoneal infection model reveals that host resistance to Campylobacter jejuni is Nramp1 dependent. Microbes and Infection 10:922-927, 2008.

Menendez A., D. A. Calarese, R. L. Standfield, K. C. Chow, C. N. Scanlan, R. Kunert, H. Katinger, D. R. Burton, I. A. Wilson & J.K. Scott. A peptide inhibitor of HIV-1 neutralizing antibody 2G12 is not a structural mimic of the natural carbohydrate epitope on gp120. The FASEB Journal 22:1380-1392, 2008.

Menendez A. & B. Brett Finlay. Defensins in the immunology of bacterial infections. Current Opinion in Immunology 19:385-391, 2007.

E. Ollmann Saphire, M. Montero, Menendez A., N. E.van Houten, R. Pantophlet, M. B. Zwick, P. W.H.I. Parren, D. R. Burton, J. K. Scott & I. A. Wilson. Structure of a high-affinity "mimotope" peptide bound to HIV-1-neutralizing antibody b12 explains its inability to elicit gp120 cross-reactive antibodies.  Journal of Molecular Biology, 369:696-709, 2007.

van Houten, N.E., Zwick, M.B., Menendez A., and Scott, J.K. Filamentous phage as an immunogenic carrier to elicit focused antibody responses against a synthetic peptide. Vaccines 24:4188-4200, 2006.