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Carmen Gianfrani

Research Focus : Mucosal Immunology

Dr Gianfrani, coordinator of Mucosal Immunology Group (MIG), has a long experience in the field of interaction between food proteins and gastrointestinal immune system. Her scientific interests are mainly focused on the disregulation of immune tolerance to wheat gluten, causing celiac disease, and on molecular and cellular strategies to recover oral tolerance to dietary proteins, and to maintain gut homeostasis. Particularly, Dr Gianfrani has contributed to develop biochemical strategies to detoxify wheat gluten that are currently in clinical trials. 

Dr Gianfrani has been working in collaboration with several international research groups, either in USA and in Australia, whose laboratories has frequently visited during the last years. She is author of more than 60 original papers and reviews in international journals, as well as of book chapters on mucosal immunology and organic chemistry. Furthermore, she is reviewer for several Journals in Gastroenterology and Immunology fields, and member of Italian Society of Immunology and Clinical Allergology – SIICA; member of Scientific Board of European Laboratory for the Study of Food Induced Diseases (ELFID), University “Federico II” of Naples, and expert member of Italian Association of Celiac Disease Patients (AIC/FC). Dr Gianfrani obtained the National Academic Qualification as Associate Professor in Applied Biology, and as Associate Professor in Pathology. Dr Gianfrani has coordinated the IBP science outreach program since 2015 to July 2018, and is Editor of Pediatric Research (gastroenterology section) since 2011.

 

Dr Gianfrani’s research lines 

  • Immune pathogenesis of celiac disease and pediatric inflammatory bowel disease

  • Role of HLA class II gene expression in shaping the pathogenic immune response in celiac disease and type 1 diabetes

  • Characterization of gluten peptides stimulating CD4+ and CD8+ T cell response in celiac disease patients  

  • Enzymatic and biochemical strategies to detoxify wheat gluten

  • Identification of ancient wheat crops with reduced content of toxic gluten sequences and with high in vivo digestibility

     

Main achievements and related publications

Characterization of cytotoxic CD8+ T cells restricted by HLA-Class I molecules in celiac disease. The Mucosa Immunology Lab has investigated, during the last decade, the antigen specificity, phenotype, and biological function of CD8+ T lymphocytes infiltrating celiac intestinal mucosa that contribute to villous atrophy (Picascia et al. J Immunol 2017; Gianfrani et al.J Immunol 2003; Mazzarella et al.Gastroenterology 2008).

Identification of the repertoire of gluten immunodominant peptides stimulating CD4+ T cells inflammatory response in celiac patients. These studies have gained further insight on the peptides responsible for gut inflammation in celiac disease (Gianfrani et al. J Immunol 2003; Camarca et al. J Immunol 2009; Sollid et al. Immunogenetics 2012).

Discovery of IL-10 secreting regulatory Tr1 cells, as innate counter-regulatory cellular mechanisms to suppress inflammatory T cells responses to gluten in the intestinal mucosa of celiac disease patients (Gianfrani et al.J Immunol 2006; Battaglia et al.NYAS 2006). These studies provide a proof of concept for immunotherapeutic strategies for celiac disease treatment.

Development of biochemical strategies to detoxify wheat gluten, and characterization of ancient wheat crops with reduced or null content of gluten toxic sequences. (Gianfrani et al.Gastroenterology 2007; Gianfrani et al.Mol Nutr Food Res  2015; Gianfrani et al.Am J Clin Nutr 2013).

Role of ATG16L1 gene polymorphisms in autophagy alteration in paediatric cohort with inflammatory bowel disease (Strisciuglio et al.Inflamm Bowel Dis 2015; Strisciuglio et al.Inflamm Bowel Dis 2013).

 

Main fundings (PI Dr Gianfrani)

  • MIUR PNR 2011-2013. Flagship Interomics 2017. Project title: Multi-Omics analysis of HLA class II risk genes in relation to inflammatory responses in celiac disease (MoHLACeDi).
  • Italian Ministry of Health. Bando finalizzata 2016. Project title, Innovative Regulatory Cell-Based Strategies to Cure Celiac Disease. The project is done in collaboration with San Raffaele Hospital, Milano.
  • Life Science Discovery Fund Authority (LSDF) 2015 - University of Washington, Seattle, USA. Project title: Launch of the Institute of Protein Design for creative new therapeutics, vaccines, and diagnosis.
  • MIUR PNR 2011-2013. Flagship Projects Interomics 2015. Project title: Analysis of HLA Ribonome in Celiac Disease in Relation to the Anti-Gluten Immune Response (RiCeDi).
  • National Health and Medical Research Council Australia – NHMRC, 2012. Project title: “Epitope spreading and the immune response to gluten in coeliac disease”.
  • Miur, Prin 2009. Project title: “Interaction between innate and adaptive immunity in the pathogenesis of celiac disease”.

Selected 10 publications

  • Gianfrani C, Pisapia L, Picascia S, Strazzullo M, Del Pozzo G. Expression level of risk genes of MHC class II is a susceptibility factor for autoimmunity: New insights. J Autoimmun 2018; Jan 10. pii: S0896-8411(17)30626-1. doi: 10.1016/j.jaut.2017.12.016. 
  • Pisapia L, Camarca A, Picascia S, Bassi V2, Barba P, Del Pozzo G, Gianfrani C. HLA-DQ2.5 genes associated with celiac disease risk are preferentially expressed with respect to non-predisposing HLA genes: Implication for anti-gluten T cell response. J Autoimmun 2016; Jun;70:63-72. doi: 10.1016/j.jaut.2016.03.016.  
  • Gianfrani C, Camarca A, Mazzarella G, Di Stasio L, Rotondi Aufiero V, Giardullo N, Ferranti P, Picariello G, Picascia S, Troncone R, Auricchio S, Mamone G. Extensive in vitro gastrointestinal digestion markedly reduces the immune-toxicity of Triticum monococcum wheat: implication for celiac disease. Mol Nutr & Food Res 2015; Sep;59(9):1844-54. doi: 10.1002/mnfr.201500126.  
  • Strisciuglio C, Miele E, Giugliano F, Vitale S, Andreozzi ML, Vitale A, Catania MR, Staiano A,  Troncone R, Gianfrani C. Bifidobacteria enhance antigen sampling and processing by dendritic cells in pediatric IBD. Inflamm Bowel Dis 2015; Jul;21(7):1491-8. doi: 10.1097/MIB.0000000000000389. 
  • Tye-Din J, Stewart J, Dromey J, Beissbarth T, van Heel D, Tatham A, Henderson K, Mannering S, Gianfrani C, Jewell D, Hill A, McCluskey J, Rossjohn J, and Anderson R. Design of peptide-based immunotherapy and diagnostics for celiac disease based upon comprehensive, quantitative mapping of T-cell epitopes in gluten. Sci Transl Med 2010; 2:41. doi: 10.1126/scitranslmed.3001012. 
  • Camarca A, Anderson RP, Mamone G, Fierro O, Facchiano A, Costantini S, Zanzi D, Sidney J, Auricchio S, Sette A, Troncone R,  and Gianfrani C. Intestinal T-cell responses to gluten peptides are largely heterogeneous: implication for a peptide-based therapy in celiac disease. J Immunol 2009; 182:4158-4166. doi: 10.4049/jimmunol.0803181. 
  • Mazzarella G,  Stefanile R, Camarca A, Giliberti P, Casentini E, Marano C, Iaquinto G, Giardullo N, Auricchio S, Sette A, Troncone R, Gianfrani C. Gliadin activates HLA Class I-restricted CD8+ T-cells in coeliac intestinal mucosa and induces the enterocyte apoptosis. Gastroenterology 2008; 134:1017-1027. doi: 10.1053/j.gastro.2008.01.008. 
  • Gianfrani C, Siciliano R, Facchiano A, Camarca A, Mazzeo M, Costantini S, Salvati V, Maurano F, Mozzarella G, Iaquinto G, Bergamo P, Rossi M. Transamidation of wheat flour inhibits the response to gliadin of intestinal T cells in celiac disease. Gastroenterology2007; 133:780-789.  
  • Gianfrani C, Levings M, Sartirana C, Mazzarella G, Barba G, Zanzi D, Camarca A,  Iaquinto G, Giardullo N, Auricchio S, Troncone R, and Roncarolo MG. Gliadin-specific type-1 regulatory T cells from intestinal mucosa of treated celiac patients inhibit pathogenic T cells. J Immunol 2006; 177:4178. 
  • Gianfrani C, Troncone R, Mugione P, Cosentini E, De Pascale M, Faruolo C, Senger S, Terrazzano G, Southwood S, Auricchio S, Sette A. Coeliac Disease association with CD8+ T cell responses: identification of a novel gliadin-derived HLA-A2 restricted epitope. J Immunol2003;170:2719-2726. 

Group

Stefania Picascia   PhD        Maria Vittoria Laezza    ungraduated    
Serena VitalePhD Angela Di Pasqualeungraduated

 

Currently, Dr Gianfrani is Editor of Pediatric Research (gastroenterology section), coordinator of the SIICA Campania Section and of IBP Science Outreach Program (http://www.ibp.cnr.it/education/training-for-schools).