I have a longstanding experience in studies on CLL pathogenesis and on the role of antigen-selection in lymphoid malignancies.
Most of my scientific studies have been (and are) related to lymphoproliferative disorders and more specifically on the role of antigen stimulation in B-cell derived lymphoma/leukemias (Burkitt Lymphoma, Primary Effusion Lymphoma and Chronic Lymphocytic Leukemia).
I believe that the my most important study is the one describing, for the first time, that CLL IGHV regions are composed of somatically mutated and unmutated in similar proportion [PMID: 9788964]. This notion has been widely confirmed and its relevance has been reinforced by the finding that IGHV mutational status is an important and independent prognostic factor [PMID: 10477712]. These studies have also provided the first evidence that CLL IGHV repertoire is non-random.
More recently, my group focused on studies that evaluated the effects of drugs (Metformin and Fenretinide) on CLL cells highlighting the diverse sensitivity between resting/activated and proliferating CLL cells [PMID: 22475870 and 26265439]. In addition, I have been actively involved in studies related to the use of small non coding RNAs to induce CLL cells cycle arrest and apoptosis [PMID: 28053325]. These studies are being developed in CLL patient-derived xenografts. Indeed, we have achieved great confidence with this animal model [PMID: 27430522] that can be used to investigate several CLL disease related aspects and for drug testing.
1989: M. Sc. in Biological Sciences, University of Genoa, Italy.
1994: PhD in Immunological Sciences, University of Genoa, Italy
2001: Post-graduation (‘Specialization’) in Allergology and Clinical Immunology, University of Genoa, Italy
Positions and Honors
2007 - presently: Head of the research group Molecular Immunology and Oncology (MIaO) lab at the Human Anatomy Section of the Department of Experimental Medicine, University of Genoa.
2015 - presently: Head of the Molecular Pathology Unit at the IRCCS – Policlinico San Martino, Genoa.
2005 - presently: Associate Professor of Human Anatomy at the University of Genoa.
2000 - 2005: Senior investigator at the Section of Human Anatomy, Department of Experimental Medicine, University of Genoa.
1996-1999: Post doctoral fellowship at the laboratory of Clinical Immunology (National Institute for Cancer Research, Genoa, Italy)
1994 - 1996: Post doctoral fellow at the laboratory of Rheumatology and Clinical Immunology (North Shore Hospital, Manhasset, NY)
1991 - 1994: Ph.D. student at the laboratory of Clinical Immunology (National Institute for Cancer Research, Genoa, Italy)
1988 - 1990: Internal student, Laboratory of Immunogenetics, National Institute for Cancer Research, Genoa, Italy
2007 - presently: Italian Society of Histology and Anatomy
2013 - presently: The American Association of Immunologists
April 2017 - Marie Sklodowska-Curie Actions Seal of Excellence for MSCA individual fellowships call.
Recent Research Grants (PI)
2015 - 2017 AIRC (Associazione Italiana Ricerca Cancro) “3D structure analysis of Chronic Lymphocytic Leukemia B-cell Receptor: biological and clinical relevance.
2010 - 2012 AIRC (Associazione Italiana Ricerca Cancro) “3D structure analysis of Chronic Lymphocytic Leukemia B-cell Receptor: biological and clinical relevance”.
2009 - 2011: Compagnia di S. Paolo (Turin, Italy) for a coordinated project: “Antigen-dependent and-independent mechanisms involved in the pathogenesis of Chronic Lymphocytic Leukemia”.
Selected publications (among 55 peer-reviewed articles, total citations n=4070)
Cutrona G, Matis S, Colombo M, Massucco C, Baio G, Valdora F, Emionite L, Fabris S, Recchia AG, Gentile M, Neumaier CE, Reverberi D, Massara R, Boccardo S, Basso L, Salvi S, Rosa F, Cilli M, Zupo S, Truini M, Tassone P, Calabrese M, Negrini M, Neri A, Morabito F, Fais F, Ferrarini M. 2017. Effects of miRNA-15 and miRNA-16 expression replacement in chronic lymphocytic leukemia: Implication for therapy. Leukemia
Valdora F, Cutrona G, Matis S, Morabito F, Massucco C, Emionite L, Boccardo S, Basso L, Recchia AG, Salvi S, Rosa F, Gentile M, Ravina M, Pace D, Castronovo A, Cilli M, Truini M, Calabrese M, Neri A, Neumaier CE, Fais F, Baio G, Ferrarini M. 2016. A non-invasive approach to monitor chronic lymphocytic leukemia engraftment in a xenograft mouse model using ultra-small superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI). Clin Immunol
Bruno S, Ledda B, Tenca C, Ravera S, Orengo AM, Mazzarello AN, Pesenti E, Casciaro S, Racchi O, Ghiotto F, Marini C, Sambuceti G, DeCensi A, Fais F. 2015. Metformin inhibits cell cycle progression of B-cell chronic lymphocytic leukemia cells. Oncotarget 6: 22624-40
Sangaletti S, Tripodo C, Vitali C, Portararo P, Guarnotta C, Casalini P, Cappetti B, Miotti S, Pinciroli P, Fuligni F, Fais F, Piccaluga PP, Colombo MP. 2014. Defective stromal remodeling and neutrophil extracellular traps in lymphoid tissues favor the transition from autoimmunity to lymphoma. Cancer Discov 4: 110-29
Marcatili P, Ghiotto F, Tenca C, Chailyan A, Mazzarello AN, Yan XJ, Colombo M, Albesiano E, Bagnara D, Cutrona G, Morabito F, Bruno S, Ferrarini M, Chiorazzi N, Tramontano A, Fais F. 2013. Igs expressed by chronic lymphocytic leukemia B cells show limited binding-site structure variability. J Immunol 190: 5771-8
Colombo M, Cutrona G, Reverberi D, Bruno S, Ghiotto F, Tenca C, Stamatopoulos K, Hadzidimitriou A, Ceccarelli J, Salvi S, Boccardo S, Calevo MG, De Santanna A, Truini M, Fais F, Ferrarini M. 2013. Expression of immunoglobulin receptors with distinctive features indicating antigen selection by marginal zone B cells from human spleen. Mol Med 19: 294-302
Bruno S, Ghiotto F, Tenca C, Mazzarello AN, Bono M, Luzzi P, Casciaro S, Recchia A, Decensi A, Morabito F, Fais F. 2012. N-(4-hydroxyphenyl)retinamide promotes apoptosis of resting and proliferating B-cell chronic lymphocytic leukemia cells and potentiates fludarabine and ABT-737 cytotoxicity. Leukemia 26: 2260-8
Ghiotto F, Marcatili P, Tenca C, Calevo MG, Yan XJ, Albesiano E, Bagnara D, Colombo M, Cutrona G, Chu CC, Morabito F, Bruno S, Ferrarini M, Tramontano A, Fais F, Chiorazzi N. 2011. Mutation pattern of paired immunoglobulin heavy and light variable domains in chronic lymphocytic leukemia B cells. Mol Med 17: 1188-95
Colombo M, Cutrona G, Reverberi D, Fabris S, Neri A, Fabbi M, Quintana G, Quarta G, Ghiotto F, Fais F, Ferrarini M. 2011. Intraclonal cell expansion and selection driven by B cell receptor in chronic lymphocytic leukemia. Mol Med 17: 834-9
Bagnara D, Ibatici A, Corselli M, Sessarego N, Tenca C, De Santanna A, Mazzarello A, Daga A, Corvo R, De Rossi G, Frassoni F, Ciccone E, Fais F. 2009. Adoptive immunotherapy mediated by ex vivo expanded natural killer T cells against CD1d-expressing lymphoid neoplasms. Haematologica 94: 967-74
Bagnara D, Callea V, Stelitano C, Morabito F, Fabris S, Neri A, Zanardi S, Ghiotto F, Ciccone E, Grossi CE, Fais F. 2006. IgV gene intraclonal diversification and clonal evolution in B-cell chronic lymphocytic leukaemia. Br J Haematol 133: 50-8
Fais F, Tenca C, Cimino G, Coletti V, Zanardi S, Bagnara D, Saverino D, Zarcone D, De Rossi G, Ciccone E, Grossi CE. 2005. CD1d expression on B-precursor acute lymphoblastic leukemia subsets with poor prognosis. Leukemia 19: 551-6
Messmer BT, Albesiano E, Efremov DG, Ghiotto F, Allen SL, Kolitz J, Foa R, Damle RN, Fais F, Messmer D, Rai KR, Ferrarini M, Chiorazzi N. 2004. Multiple distinct sets of stereotyped antigen receptors indicate a role for antigen in promoting chronic lymphocytic leukemia. J Exp Med 200: 519-25
Ghiotto F, Fais F, Valetto A, Albesiano E, Hashimoto S, Dono M, Ikematsu H, Allen SL, Kolitz J, Rai KR, Nardini M, Tramontano A, Ferrarini M, Chiorazzi N. 2004. Remarkably similar antigen receptors among a subset of patients with chronic lymphocytic leukemia. J Clin Invest 113: 1008-16
Fais F, Morabito F, Stelitano C, Callea V, Zanardi S, Scudeletti M, Varese P, Ciccone E, Grossi CE. 2004. CD1d is expressed on B-chronic lymphocytic leukemia cells and mediates alpha-galactosylceramide presentation to natural killer T lymphocytes. Int J Cancer 109: 402-11
Bruno S, Ghiotto F, Fais F, Fagioli M, Luzi L, Pelicci PG, Grossi CE, Ciccone E. 2003. The PML gene is not involved in the regulation of MHC class I expression in human cell lines. Blood 101: 3514-9
Damle RN, Ghiotto F, Valetto A, Albesiano E, Fais F, Yan XJ, Sison CP, Allen SL, Kolitz J, Schulman P, Vinciguerra VP, Budde P, Frey J, Rai KR, Ferrarini M, Chiorazzi N. 2002. B-cell chronic lymphocytic leukemia cells express a surface membrane phenotype of activated, antigen-experienced B lymphocytes. Blood 99: 4087-93
Damle RN, Fais F, Ghiotto F, Valetto A, Albesiano E, Wasil T, Batliwalla FM, Allen SL, Schulman P, Vinciguerra VP, Rai KR, Gregersen PK, Ferrarini M, Chiorazzi N. 2000. Chronic lymphocytic leukemia: a proliferation of B cells at two distinct stages of differentiation. Curr Top Microbiol Immunol 252: 285-92
Fais F, Ghiotto F, Hashimoto S, Sellars B, Valetto A, Allen SL, Schulman P, Vinciguerra VP, Rai K, Rassenti LZ, Kipps TJ, Dighiero G, Schroeder HW, Jr., Ferrarini M, Chiorazzi N. 1998. Chronic lymphocytic leukemia B cells express restricted sets of mutated and unmutated antigen receptors. J Clin Invest 102: 1515-25
Fais F, Sellars B, Ghiotto F, Yan XJ, Dono M, Allen SL, Budman D, Dittmar K, Kolitz J, Lichtman SM, Schulman P, Schuster M, Vinciguerra VP, Rai K, Stevenson FK, Gregersen PK, Ferrarini M, Chiorazzi N. 1996. Examples of in vivo isotype class switching in IgM+ chronic lymphocytic leukemia B cells. J Clin Invest 98: 1659-66
Efremov DG, Ivanovski M, Siljanovski N, Pozzato G, Cevreska L, Fais F, Chiorazzi N, Batista FD, Burrone OR. 1996. Restricted immunoglobulin VH region repertoire in chronic lymphocytic leukemia patients with autoimmune hemolytic anemia. Blood 87: 3869-76