Mantovani Alberto, MD

Mantovani Alberto, MD

Alberto Mantovani (6)_ok

Role: Scientific Director 
Hospital: Humanitas Clinical and Research Center, Italy

Role: Full Professor of General Pathology
University: University of Milan, Italy

alberto.mantovani@humanitasresearch.it

SCOPUS Author ID
7201774556

 

Education

1973: M.D., University of Milan, Italy
1976: Specialist in Oncology, University of Pavia, Italy

Honors

1973: Graduate summa cum laude
1973: Fellow of the Italian Association Against Leukemias
1974: Fellow of the Anna Villa Rusconi Foundation
1975: Fellowship from the British Council
1978: Yamagiwa – Yoshida International Study grant from UICC, Geneva, Switzerland
1979: Awarded a NATO fellowship
1987: Eleanor Roosvelt UICC fellow
1998: Biotec Award
2000: Marie T. Bonazinga Award, Boston, USA
2003: Otto Hertz Lecturer, Tel Aviv
2004: Guido Venosta Award for Cancer Research by the President of the Republic of Italy
2004: Walter Cottman Lecturer, Monash University, Melbourne, Australia
2005: Premio Ippocrate per la Ricerca Biomedica
2006: “Onorificenza al Merito della Repubblica Italiana”  (Commendatore) for scientific contribution by the President of  the Republic of Italy
2006: European Federation of Immunological Societies – Schering Plough, 1st European Immunology Prize, Paris, France
2006: XIV Premio per la Ricerca Finalizzata alla Lotta Contro i Tumori, Fondazione Cassa di Risparmio di Asti
2007: Galileo Galilei Prize for Research in Biomedical Sciences (International Jury composed by Ronald B Herberman, Stuart A Aaronson, Klas Karre, Reinhold E Schmidt)
2007: Premio PISO (international Jury composed by past awardees: Luc Montagnier, Anthony Fauci,Lorenzo  Moretta, P. Mannuccio Mannucci)
2009: William Harvey Award, Oustanding Scientist 2009, London, UK.
2010: Paul Kallos Lecturer, Collegium Internationale Allergologicum
2011: IMID Award for Excellence in Immunology
2012: Hans J. Müller-Eberhard Lecturer, Complement Workshop, Crete
2012: Premio Nazionale “L’Altra Italia … Vite da Premio”
2013: Frontiers in Digestive Health Distinguished Guest Speake

Research Experience

1973-1975: Research assistant Department of Tumor Immunobiology and Chemotherapy, Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy.

1975-1976: Visiting fellow at the Department of Tumor Immunology,Chester Beatty Research Institute, Belmont, Sutton, Surrey,England.

1978 and 1979: Visiting fellow at the Laboratory of Immunodiagnosis, NIH,Bethesda, MD., USA, supported by a NATO Grant.

1979-1981: Senior investigator, Department of Tumor Immunology and Chemotherapy, Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy.

1981: Chief, Laboratory of Immunology, Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy.

1987: Eleanor Roosvelt UICC Scholar, Laboratory of Molecular Immunoregulation, NIH, Frederick, MD., USA.

1994 to 2001: Full Professor of General Pathology, School of Medicine, University  of Brescia, Italy.

1996 to 2005: Head, Department of Immunology and Cell Biology, Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy.

2001 to date: Full Professor of General Pathology, School of Medicine, State University of Milan, Italy

Sept. 2005 to date: Scientific Director, Istituto Clinico Humanitas and President,  Fondazione Humanitas per la Ricerca

Main contributions

Tumor biology.  Demonstration in the late ‘70s of the protumor function of tumor-associated macrophages (TAM) linking inflammation and cancer (reviewed in Balkwill and Mantovani, Lancet, 2001). TAM as a prototypic M2 population (Mantovani et al., Nature 2008; Balkwill et al., Cancer Cell 2005).  First molecular linking of a genetic event (RET/PTC rearrangement) sufficient  to cause cancer in humans to the construction of an inflammatory microenvironment (Borrello et al., PNAS 2005). Proof of principle that targeting tumor promoting macrophages has therapeutic value in humans (Germano et al, Cancer Cell 2013). Alberto Mantovani is recognized as a forerunner in the ‘70s and a founding father of the renaissance of the inflammation-cancer connection.

Chemokines. Original description and role in TAM recruitment of a unique monocyte attractant, Monocyte Chemotactic  Protein-1 (CCL2), as tumor-derived chemotactic factor (Bottazzi et al, Science 1983). Characterization of chemokines and role in pathophysiology, including dendritic cell and polarized T cell migration. Induction of chemokine production by IL-6 in endothelial cells via trans-signaling, a key component of chronic inflammation (Romano et al, Immunity 1997). Characterization of D6 as a decoy receptor for inflammatory CC chemokines (Mantovani et al, Nature Rev. Immunol 2006).

IL-1/Toll-like receptors (TLR). Endothelial cell activation by IL-1 and cytokines (Rossi et al., Science 1985; Bussolino et al, Nature 1989; Romano et al, Immunity 1997). Identification of the type II receptor as a decoy receptor, a novel concept in biology (Colotta et al, Science 1993); the discovery of a decoy receptor represented a paradigm shift after the original definition of the concept of “receptor” by Langley at the end of the 19th century; decoy receptors are now recognized as a general,  evolutionary conserved strategy to tune cytokines, chemokines and growth factors. Cloning of an intracellular isoform of the IL-1 receptor antagonist (Muzio et al., J. Exp. Med.  1995). First demonstration of MyD88 as the adaptor of mammalian Toll-Like Receptors (TLR) and identification of downstream transducers (Muzio et al., J. Exp. Med. 1998).Cloning and characterization of TIR8/SIGIRR, a negative regulator of IL-1 receptor and TLR signalling (Garlanda et al., Trends Immunol. 2009).

Humoral innate immunity: cloning (cDNA and genomic, mouse and human), structural and functional characterization of the first long pentraxin PTX3 (Garlanda et al, Nature 2002; Jeannin et al, Immunity 2005; Deban et al, Nature Immunol. 2010); structural immunobiology; role as a paradigm for humoral innate immunity; diagnostic and therapeutic translation (ongoing).

Contribution to Public Awareness  of Science

Alberto Mantovani has been actively involved in the fostering of science and scientific policy in Italy at various levels, with a focus on Immunology, Vaccines, Public Health, and Biomedicine, taking public stands on several issues  including quackery whenever appropriate. He regularly contributes to the most authoritative Italian daily newspapers (eg Corriere della Sera; Il Sole 24 Ore) and magazines (Espresso and Panorama). He wrote a book  (I Guardiani della Vita, Dalai Editore, 2011) on Immunology and Health targeted to lay public and contributed to scientific (eg SuperQuark; TGR Leonardo; Radiotre Scienza) and general radio and television programs. To promote science awareness and policy he cofounded the association “ Gruppo2003” of Italian highly cited scientists (http://www.gruppo2003.it) and together with astrophysicist Tommaso Maccacaro founded the website http://www.scienzainrete.it.

Impact

For several years now, bibliometric analyses have indicated that he is the most quoted italian scientist.  He has over 60.00 citations. A recent ranking indicates that he is the most quoted Italian scientist working in Italy (http://www.topitalianscientists.org/Top_italian_scientists_VIA-Academy.aspx;) and one of the 10 most quoted immunologists (H-index ISI 108; Scopus 123; Google Scholar: 141) http://www.tisreports.com/products/19-Top_scientists_in_the_world___the_Via_academy_compilation.aspx).

Selected publications

Originals

Jaillon S,  Moalli F,  Ragnarsdottir B, Bonavita E, Riva F, Barbati E, Nebuloni M, Krajinovic LC, Markotic A, Valentino S, Doni A, Tartari S, Graziani G, Montanelli A, Delneste Y, Svanborg C, Garlanda C, Mantovani A.  The humoral pattern recognition molecule PTX3 is a key component of innate immunity against urinary tract infection. Immunity, in press.

Cunha C, Aversa F, Lacerda JF, Busca A, Kurzai O, Grube M, Löffler J, Maertens JA,  Bell AS, Inforzato A, Barbati E, Almeida B, Santos e Sousa P, Barbui A, Potenza L, Caira M, Ph.D., Rodrigues F, Salvatori G, Pagano L, Luppi M, Mantovani A,Velardi A, Romani L, Carvalho A.  Genetic deficiency of PTX3 and aspergillosis in stem cell transplantation. New Engl J Med, 370:421-432, 2014.

Germano G, Frapolli R, Belgiovine C, Anselmo A, Pesce S, Liguori M, Erba E, Uboldi S, Zucchetti M, Pasqualini F, Nebuloni M, van Rooijen N, Mortarini R, Beltrame L, Marchini S, Fuso Nerini I, Sanfilippo R, Casali PG, Pilotti S, Galmarini CM, Anichini A, Mantovani A, D’Incalci M, Allavena P. Role of macrophage targeting in the antitumor activity of trabectedin. Cancer Cell 23: 249-262, 2013.

Deban L, Castro Russo R, Sironi M, Moalli F, Scanziani M, Zambelli V, Cuccovillo I, Bastone A, Gobbi M, Valentino S, Doni A, Garlanda C, Danese S, Salvatori G, Sassano M, Evangelista V, Rossi B,  Zenaro E, Constantin G, Laudanna C, Bottazzi B, Mantovani A
Binding to P-selectin and regulation of leukocyte recruitment by the long pentraxin PTX3, a key component of humoral innate immunity. Nature Immunol, 11: 328-334, 2010.

Di Liberto D, Locati M, Caccamo N, Vecchi A, Meraviglia S, Salerno A, Sireci G, Nebuloni M, Cardona P-J, Dieli F, Mantovani A.  Role of the chemokine decoy receptor D6 in balancing inflammation, immune activation and antimicrobial resi stance in Mycobacterium tuberculosis infection.  J. Exp. Med. 205: 2075-2084, 2008

Lech M,Kulkarni OP, Pfeiffer S, Savarese E, Krug A, Garlanda C, Mantovani A, Anders H-J  Tir8/Sigirr prevents murine lupus by suppressing the immunostimulatory effects of lupus autoantigens.  J. Exp. Med. 205: 1879-1888, 2008.

Jaillon S, Peri G, Delneste Y, Frèmaux I, Doni A, Moalli F, Garlanda C, Romani L, Gascan H, Bellocchio S, Bozza S, Cassatella MA, Jeannin P, Mantovani A.  The humoral pattern recognition receptor PTX3 is stored in neutrophil granules and localized in extracellular traps.   J. Exp. Med., 204, 793-804, 2007.

Martinez de la Torre Y, Buracchi C, Borroni EM, Dupor J,  Bonecchi R, Nebuloni M, Pasqualini F, Doni A, Lauri E et al.  Protection against inflammation- and autoantibody- caused fetal loss by the chemokine decoy receptor D6. PNAS 104:2319-2324, 2007

Biswas SK, Gangi L, Paul S, Schioppa T, Saccani A, Sironi M, Bottazzi B, Doni A, Vincenzo B, Pasqualini F, Vago L, Nebuloni M, Mantovani A*, Sica A. (* corresponding author). A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation). Blood 107:2112-2122, 2006.

Borrello MG, Alberti L, Fischer A, Degl’InnocentiD, Ferrario C, Gariboldi M, Marchesi F, Allavena P, Greco A, Collini P, Pilotti S, Cassinelli G, Bressan P, Fugazzola L, Mantovani A*, Pierotti M*  (*corresponding authors).  Induction of a proinflammatory programme in normal human thyrocytes by the RET/PTC1 oncogene.  PNAS, 102:  14825-14830, 2005.

Jeannin P., Bottazzi B., Sironi M., Doni A., Rusnati M., Presta M., Maina V., Magistrelli G., Haeuw J.F., Hoeffel G., Thieblemont N., Corvaia N., Garlanda C., Delneste Y., Mantovani A.  Complexity and complementarity of outer membrane protein-A recognition by cellular and humoral innate immunity receptors  Immunity 22: 551-560, 2005.

Bertini R, Allegretti M, Bizzarri C, Moriconi A, Locati M, Zampella G, Cervellera M N, Di Cioccio V, Cesta M C, Galliera E, Martinez F O, Di Bitondo R, Troiani G, Sabbatini V, Anacardio R, Cutrin J C, Cavalieri B, Mainiero F, Strippoli R, Villa P, Di Girolamo M, Martin F, Gentile M, Santoni A, Corda D, Ghezzi P, Poli Giuseppe, Mantovani A, Colotta F.    A new class of non-competitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: Prevention of reperfusion injury.  Proc Natl Acad Sci USA  101: 11791-11796, 2004

Garlanda C, Riva F, Polentarutti N, Buracchi C, Sironi M, De Bortoli M., Muzio M, Bergottini R, Scanziani E, Vecchi A, Hirsch E, Mantovani A   Intestinal inflammation in mice deficient in TIR8, an inhibitory member of the IL-1 receptor family.  Proc Natl Acad Sci USA  101: 3522-3526, 2004

Schioppa T., Uranchimeg B., Saccani A., Biswas S.,  Doni A., Rapisarda A., Bernasconi S., Saccani S., Nebuloni M., Vago L., Mantovani A., Melillo G., Sica A.  Regulation of the chemokine receptor CXCR4 by hypoxia.  J. Exp. Med. 198: 1391-1402, 2003

Wittamer V, Franssen J D, Vulcano M, Mirjolet J F, Le Poul E, Migeotte I, Brezillon S, Tyldesley R, Blanpain C, Detheux M, Mantovani A, Sozzani S, Vassart G, Parmentier M, Communi D.  Specific recruitment of antigen-presenting cells by Chemerin, a novel processed ligand from human inflammatory fluids.  J Exp Med  198: 977-985, 2003

Garlanda C., Hirsch E., Bozza S., Salustri A., De Acetis M., Nota R., Maccagno A., Riva F., Bottazzi B., Peri G., Doni A., Vago L., Botto M., De Santis R., Carminati P., Siracusa G., Altruda A., Vecchi A., Romani L., Mantovani A.  Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response. Nature 420: 182-186, 2002.

Fraticelli P, Sironi M, Bianchi G, D’Ambrosio D, Albanesi C, Stoppacciaro A, Chieppa M, Allavena P, Ruco L, Girolomoni G, Sinigaglia F, Vecchi A, Mantovani A   Fractalkine (CX3CL1) as an amplification circuit of polarized Th1 responses.  J Clin Invest. 107: 1173-1181, 2001

D’Amico G, Frascaroli G, Bianchi G, Doni A, Transidico P, Vecchi A, Sozzani S, Allavena P, Mantovani A. Uncoupling of inflammatory chemokine receptors by interleukin 10: Generation of functional decoys. Nature Immunol. 1: 387-391, 2000.

Hirsch E, Katanaev V L, Garlanda C, Azzolino O, Silengo L, Sozzani S, Mantovani A, Altruda F, Wymann M P. Central role for G protein-coupled phosphoinositide 3-kinase  in inflammation.Science 287: 1049-1053, 2000.

Muzio M, Natoli G, Saccani S, Levrero M, Mantovani A.. The human Toll signaling pathway: Divergence of nuclear factor Kb and JNK/SAPK activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6).   J. Exp. Med.  187: 2097-2101, 1998.

Sozzani S, Allavena P, D’Amico G, Luini W, Bianchi G, Kataura M, Imai T, Yoshie O, Bonecchi R, Mantovani A.. Differential regulation of chemokine receptors during dendritic cell maturation: A model for their trafficking properties.  J. Immunol. 161: 1083-1086, 1998.

Sozzani, S., S. Ghezzi, G. Iannolo, W. Luini, A. Borsatti, N. Polentarutti, A. Sica, M. Locati, C. Mackay, T. N. C. Wells, P. Biswas, E. Vicenzi, G. Poli, and A. Mantovani.. Interleukin-10 increases CCR5 expression and HIV infection in human monocytes. J. Exp. Med. 187:439-444, 1998

Bonecchi R, Bianchi G, Panina Bordignon P, D’Ambrosio D, Lang R, Borsatti A, Sozzani S, Allavena P, Gray P A, Mantovani A, Sinigaglia F..Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s.   J. Exp. Med. 187: 129-134, 1998.

Romano M, Sironi M, Toniatti C, Polentarutti N, Fruscella P, Ghezzi P, Faggioni R, Luini W, Van Hinsberg V, Sozzani S, Bussolino F, Poli V, Ciliberto G, Mantovani A.  Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment.  Immunity  6: 315-325, 1997.

Godiska R, Chantry D, Raport C J, Sozzani S, Allavena P, Leviten D, Mantovani A, Gray P W..Human macrophage-derived chemokine (MDC), a novel chemoattractant for monocytes,monocyte-derived dendritic cells, and natural killer cells.  J. Exp. Med. 185: 1595-1604, 1997.

Sica, A., A. Saccani, A. Borsatti, C. A. Power, T. N. C. Wells, W. Luini, N. Polentarutti, S. Sozzani, and A. Mantovani.. Bacterial lipopolysaccharide rapidly inhibits expression of C-C chemokine receptors in human monocytes . J. Exp. Med. 185:969-974, 1997.

Re, F., M. Sironi, M. Muzio, C. Matteucci, M. Introna, S. Orlando, G. Penton-Rol, S. K. Dower, J. E. Sims, F. Colotta, and A. Mantovani. Inhibition of interleukin-1 responsiveness by type II receptor gene transfer: a surface “receptor” with anti-interleukin-1 function. J. Exp. Med. 183: 1841-1850, 1996

Sozzani S, Sallusto F, Luini W, Zhou D, Piemonti L, Allavena P, Van Damme J, Valitutti S, Lanzavecchia A, Mantovani A. Migration of dendritic cells in response to formyl peptides, C5a, and a distinct set of chemokines. J. Immunol.. 155: 3292-3295, 1995

Colotta, F., S. Orlando, E. J. Fadlon, S. Sozzani, C. Matteucci, and A. Mantovani. Chemoattractants induce rapid release of the interleukin 1 type II decoy receptor in human polymorphonuclear cells. J. Exp. Med. 181:2181-2188, 1995.

Muzio, M., N. Polentarutti, M. Sironi, G. Poli, L. De Gioia, M. Introna, A. Mantovani, and F. Colotta. Cloning and characterization of a new isoform of the interleukin-1  receptor antagonist. J. Exp. Med. 182:623-628, 1995

Colotta, F., F. Re, M. Muzio, R. Bertini, N. Polentarutti, M. Sironi, J. G. Giri, S. K. Dower, J. E. Sims, and A. Mantovani. Interleukin-1 type II receptor: a decoy target for IL-1 that is regulated by IL-4. Science  261: 472-475, 1993

Bussolino, F., J. M. Wang, P. Defilippi, F. Turrini, F. Sanavio, C. J. Edgell, M. Aglietta, P. Arese, and A. Mantovani. Granulocyte- and granulocyte-macrophage-colony stimulating factors induce human endothelial cells to migrate and proliferate. Nature  337: 471-473. 1989.

Rossi, V., F. Breviario, P. Ghezzi, E. Dejana, and A. Mantovani.. Prostacyclin synthesis induced in vascular cells by interleukin-1. Science  229: 174-176, 1985.

Bottazzi, B., N. Polentarutti, R. Acero, A. Balsari, D. Boraschi, P. Ghezzi, M. Salmona, and A. Mantovani. Regulation of the macrophage content of neoplasms by chemoattractants. Science  220:210-212, 1983.

Reviews

Garlanda C., Dinarello C.A.,  Mantovani A. The IL-1 family: back to the future. Immunity 39: 1003-1018.

Locati M.,  Mantovani A., Sica A. Macrophage activation and polarization as an adaptive component of innate immunity. Adv. Immunol. 120: 163-184, 2013

Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest. 122: 787-795, 2012.

Biswas S.K. and  Mantovani A. Orchestration of metabolism by macrophages. Cell Metab. 15: 432-437, 2012.

Mantovani A, Cassatella MA, Costantini C, Jaillon S. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol. 11: 519-531, 2011.

Biswas S.K. and  Mantovani A.  Macrophage plasticity and interaction with lymphocyte subsets: cancer as paradigm. Nat Immunol 11: 889-896, 2010.

Bottazzi B, Doni A, Garlanda C, Mantovani A. An Integrated View of Humoral Innate Immunity: Pentraxins as a Paradigm. Annu Rev Immunol. 28:157-183, 2010.

Garlanda C, Anders HJ, Mantovani A.TIR8/SIGIRR: an IL-1R/TLR family member with regulatory functions in inflammation and T cell polarization.Trends Immunol. 30: 439-446, 2009.

Mantovani A. Cancer: Inflaming metastasis. Nature 45: 36-37, 2009.

Mantovani A, Allavena P, Sica A, Balkwill F  Cancer-Related Inflammation. Nature 454: 436-444, 2008.

Mantovani, A., Romero, P., Paluka, AK., Marincola, FM.  Tumor immunity: effector response to tumor and the influence of the microenvironment. Lancet 371:771-783, 2008.

Mantovani A, Bonecchi R, Locati M.  Tuning inflammation and immunity by chemokine sequestration: decoys and more. Nature Rev. Immunol. 6: 907-918, 2006.

Balkwill F, Charles KA, Mantovani A. Smouldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 7: 211-217, 2005.

Garlanda C.,  Bottazzi B., Bastone A.,  Mantovani A., Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility Annu. Rev. Immunol., 23: 337-366, 2005.

Mantovani A., Sica A., Sozzani S., Allavena P., Vecchi A., Locati M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 25: 677-686, 2004.

Mantovani A., Sozzani S., Locati M., Allavena P., Sica A.  Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol..23: 549-555, 2002.

Mantovani A., Locati M., Vecchi A., Sozzani S., Allavena P.  Decoy receptors as a strategy to regulate inflammatory cytokines and chemokines. Trends Immunol. 22: 328-336, 2001.

Balkwill F. and Mantovani A. Inflammation and cancer: back to Virchow?  Lancet  357: 539-545, 2001.

Mantovani A. The chemokine system: redundancy for  robust outputs. Immunol. Today  20: 254-257, 1999.

Mantovani, A., F. Bussolino, and M. Introna. Cytokine regulation of endothelial cell function: from molecular level to the bed side. Immunol. Today. 18:231-239, 1997

Colotta, F., S. K. Dower, J. E. Sims, and A. Mantovani. The type II ‘decoy’ receptor: novel regulatory pathway for interleukin-1. Immunol. Today. 15:562-566, 1994.

Mantovani, A., F. Bussolino, and E. Dejana. Cytokine regulation of endothelial cell function. FASEB. J. 6:2591-2599, 1992.

Mantovani, A., B. Bottazzi, F. Colotta, S. Sozzani, and L. Ruco. The origin and function of tumor-associated macrophages. Immunol. Today. 13:265-270, 1992.

Mantovani, A. and E. Dejana. Cytokines as communication signals between leukocytes and endothelial cells. Immunol. Today. 10:370-375, 1989.

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