Department and institution: Biotechnology and Biosciences Department, University of Milano Bicocca
Keywords: Innate Immunity, Signal Transduction, Inflammatory Diseases, Toll-Like Receptors, Tumor Models.
During the Ph.D., Ivan Zanoni (IZ) focus was to investigate the fate of auto-reactive T cells in the periphery and its consequences for autoimmune diseases. This problem was further investigated using transgenic mouse models in which antigen expression was limited to different types of antigen presenting cells. IZ also pioneered several studies on the interaction between Dendritic Cells (DCs) and Natural Killer (NK) cells during bacterial infections. DCs are sentinels of the immune system that link the innate and adaptive immune responses. During the initial phases of their activation DCs interact with NK cells and activate their anti-bacterial functions. In this context, several molecular mechanisms used by DCs have been described.
IZ has been also studying Pattern Recognition Receptor (PRRs) signaling pathways. PRRs are the receptors that initiate immunity to infection. In particular, IZ started to work on the interaction between lipopolysaccharide (LPS) and its multi-receptor complex (TLR4-MD2-CD14), identifying new signal transduction pathways specific for different cell types of the innate immune system. We have demonstrated that, in response to LPS, CD14 regulates a TLR4 independent signal transduction pathway in DCs that induces NFAT activation and that control DC’s life cycle.
Recently, we extended also to other cell types the knowledge that CD14 is able to act independently of TLR4 and that CD14 is required for the microbe-induced endocytosis of TLR4 that leads to type I interferons production, potent antibacterial and anti-tumoral mediators.
2001-2006: Ph.D. in Immunology, University of Roma “Tor Vergata”, Rome, Italy.
1996-2001: MS in Medical Biotechnology (Summa cum laude), University of Milano, Milan, Italy.
2008-Present: Assistant Professor, Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
2013-2014: Research Fellow, Prof. JC. Kagan Lab, Harvard Medical School, Children’s Hospital, Boston, USA. Field of study: signal transduction in innate immune cells, biochemistry.
2009: Visiting scientist, Prof. JC. Kagan Lab, Harvard Medical School, Children’s Hospital, Boston, USA. Field of study: signal transduction in innate immune, cell biology.
2006-2008: Post-doc, Prof. F. Granucci Lab, University of Milano-Bicocca, Milan, Italy. Field of study: In vivo mouse model of peripheral T cell tolerance. Dendritic cell and NK cell interaction studies.
2005: Visiting Scientist, Prof. U. Von Andrian Lab, Harvard Medical School, CBR Institute, Boston, USA. Field of study: In vivo multi-photon imaging technique.
Fellowships and Awards
2011: Best Abstract Awards at the SIICA-DGFI International meeting.
2009: Bioforum Junior Award as Best Italian Junior Biotechnologist, from the Italian association of Biotechnology.
2009: SIICA-Space prize for the Best research on Cytokines, from SIICA and SPACE Srl.
2009: EMBO Fellowship, from EMBO, for the project: “Study of the mechanisms through which CD14 controls the TLR4 TRAM-TRIF pathway”.
2005: EMBO Fellowship, from EMBO, for the project: “Study of cellular interactions between DCs and NK cells at the draining LN using the 2-photon microscopy”.
2005: Harlan Italy Prize, for the Best research in Experimental Immunology, from Harlan Italy.
Professional society membership
03/05-Present: SIICA, Italian Society of Immunology, Clinical Immunology and Allergology
03/12-Present: ESCI, European Society for Clinical Investigation
Commissions of Trust
-2012-2014: Topic Editor for Frontiers in Immunology
-2012-today: Reviewer for the Italian Ministry of University and Research and Ad hoc reviewer for the Wellcome Trust (UK)
-2014-Present: Editor for New Journal of Science
-Reviewer for: PLOS One, European Journal of Immunology, Annals of Microbiology, Mediators of Inflammation, Bio-protocol, Theranostics
Granted Patents and Spin Off
2012: “Nano-compounds with pharmacological activity”, Patent Application No. RM2012A000350, Rome, 19/07/2012.
2013: Spin off “inTHEna”, Nanotechnologies for Theragnostic.
1.Zanoni I*, Spreaﬁco R, Bodio C, , Cigni C, Broggi A, Gorletta T, Caccia M, Chirico G, Sironi L, Collini M, Colombo MP, Garbi N, Granucci F. “IL-15 cis-presentation is required for optimal NK Cell activation in lipopolysaccharide-mediated inﬂammatory conditions.”
Cell Reports. 2013 Sep 17. *corresponding author
2.Vitali C, Mingozzi F, Broggi A, Barresi S, Zolezzi F, Bayry J, Raimondi G, Zanoni I*, Granucci F. “Migratory, and not lymphoid-resident, dendritic cells maintain peripheral self-tolerance and prevent autoimmunity via induction of iTreg cells.”
Blood. 2012 Aug 9;120(6):1237-45. *corresponding author
3.Zanoni I, Ostuni R, Barresi S, Di Gioia M, Broggi A, Costa B, Marzi R, Granucci F. “CD14 and NFAT mediate lipopolysaccharide-induced skin edema formation in mice.”
J Clin Invest. 2012 May 1;122(5):1747-57.
4.Zanoni I, Ostuni R, Marek LR, Barresi S, Barbalat R, Barton GM, Granucci F, Kagan JC. “CD14 controls the LPS-induced endocytosis of Toll-like receptor 4.”
Cell. 2011 Nov 11;147(4):868-80.
5.Zanoni I, Ostuni R, Capuano G, Collini M, Caccia M, Ronchi AE, Rocchetti M, Mingozzi F, Foti M, Chirico G, Costa B, Zaza A, Ricciardi-Castagnoli P, Granucci F. “CD14 regulates the dendritic cell life cycle after LPS exposure through NFAT activation.”
Nature. 2009 Jul 9;460(7252):264-8.