Education:          

1971: University of Padova, graduated in chemistry cum Laude

1975: University of Padova, graduated in biology cum Laude

1975-78: long-term EMBO fellowship at the University of Cambridge, UK (PD Advisor: J.C. Metcalfe).



Positions:

1978-1983-1986: Assistant, then Associate Professor of General  Pathology, University of Padova

1986-present: Professor of General Pathology, University of Padova

1992-2011: Coordinator of the Ph.D. Course in Cell Biology of the University of Padova”.

1994-2002: Director of the National Research Council Center for Biomembranes in Padova

1999-2004: member of the EMBO Council

2001-2014: member of various Scientific Councils in Europe.

2004-2010: Deputy Director of the Scuola Galileiana of Padova

1998-on: members of the Editorial Boards of several peer-reviewed scientific journals



Performed research stages at: Institut Pasteur, Paris (1984 with J.P. Changeux and 2002 with M. Mock), University of Utrecht (1990 with Ben de Kruijff), EMBL in Heidelberg (1997 with M. Zerial), Universidad de Costa Rica (2008 with JM Gutierrez).

Prof. C. Montecucco studies the mechanisms of action of presynaptic protein neurotoxins that cause neuroparalysis and the inter-and intra-cellular signalling events that drive regeneration after peripheral neuroparalysis in mammals. 

 

Major contributions:

1986. Proposed the double "protein-and-glycolipid" model for the binding of tetanus and botulism neurotoxins to nerve terminals. This model is now fully supported by the 3D structures of the receptor binding domains of tetanus and botulinum neurotoxins.

1986-1988. Identification of active site residues of diphtheria toxin.

1987: Proposed the “cleft model” for the membrane translocation of bacterial protein toxins with intracellular targets. A similar model has been proven in 1995 for the ER translocon.

1991: discovered the zinc-endopeptidase activity of tetanus and botulinum neurotoxins

1992-1995: identified the intraneuronal targets and peptide bond specifity of tetanus and botulinum neurotoxins. This was the first and strongest demonstration of the essential role of VAMP/synaptobrevin, SNAP-25 and syntaxin in the release of neurotransmitters, and in exocytosis in general.

1993: Provided evidence that the different sensitivity of animal specifies to tetanus and botulism type B may be due to mutation of VAMP at the site of proteolytic cleavage. 

1994: bacterial toxins with intracellular activity enter cells via a four-step mechanism. All the present available experimental evidence fit in this model.

1994: Identified the SNARE motif as a major determinant in the specific recognition of the three SNARE proteins by tetanus and botulinum neurotoxins.

1993-1998: Discovered the acid activation of the VacA cytotoxin of H. pylori, the late endosomal/prelysosomal nature of the vacuoles induced by the VacA and determined some immunological and pathological consequences of the alterations of membrane trafficking at the level of late endosomes, such as the inhibition of antigen processing and of the invariant chain dependent antigen presentation. Discovered that VacA induces a specific change of the trans-epithelial resistance of epithelial cell monolayers. 

1996-1999: discovered that VacA toxin forms anion specific channels in planar lipid bilayers and on cells. 

1999-2000: Identified the neutrophil activating protein of H. pylori (HP-NAP) as a major antigen in the human response and determined its structural, biochemical and cell activation properties.

The results obtained with VacA and HP-NAP lead to the present formulation of an anti-H. pylori vaccine, containing CagA, VacA and HP-NAP, currently under clinical trial. Phase I and II clinical trials show that this vaccine is non toxic and it is highly immunogenic.

1998-2000:  co-discovered that the anthrax lethal factor is a zinc-endopeptidase specific for the MAPK kinases, which are cleaved within their N-terminus and identified the cleavage consensus motif.

2002: development of a high throughput assay of the metalloproteolytic activity of the Anthrax Lethal Factor and identified useful inhibitors.

2005: discovered the mechanism of action of the presynaptic snake PLA2 neurotoxins

2010-13: discovery that snake venom myotoxins cause entry of Ca and release of K and ATP from muscle cells and that ATP and mitochondrial components act as ALARMINS

2012-13: elaborated the mode of entry into neurons of the botulinum neurotoxins

2005-2013: developed a radial model for the nanomachine that mediates neurotransmitter release at the synapse and provided some experimental evidence.

2013: showed that ATP is involved in the immune adjuvant effect of MF59

2013-14: discovered that thioredoxin reductase and thioredoxin are present on the cytosolic surface of synaptic vesicles and that they mediate the release of tetanus and botulinum neurotoxin light chains in the cytosol. Identified several novel botulinum neurotoxin inhibitors. 

Prof. C. Montecucco present research activity continues on two lines:

 

  1. study of the mechanism of neurotoxin-induced degeneration of motoneuron axons terminals and of their regeneration
  2. definition of the molecular mechanism of action of tetanus and botulinum neurotoxins and of their target which is the  nanomachine of neuroexocytosis.

Academic Honors

1993: Award of the Shipley Institute of Medicine, Harvard Medical School for achievements in Microbial Pathogenesis.

1994: elected member of the European Molecular Biology Organization

1998: Award of the Italian Consortium for Biotechnologies for achievements in the study of bacterial toxins and vaccines. 

1999: elected member of the Academia Europeae.

2000: Award of the Deutsche Gesellschaft fur Hygiene und Mikrobiologie.

2003: Award of the Masi Foundation.

2004: Feltrinelli Prize for Pathology, Immunology and Microbiology of the Accademia dei Lincei.

2004: elected member of the German Academy of Science 

2006: elected member of the “Accademia dei Lincei” of Italy.

2008: elected member of the American Academy of Microbiology.

2009: Redi Prize of the International Society on Toxinology

2009: Hatheway medal for research on botulism of the USA Botulism InterAgencies (FDA, CDC, NIH, US Army, US Deaprtment of Agricolture and US Geological Survey)

2009: elected member of the European Academy of Microbiology

2011: Ehrlich and Darmstaedter Prize for Medicine of the Paul Ehrlich Foundation.

 

 Special Lectures, 2006-2011

 - june 1st, 2006, Keynote Lecture at the Italian Society for Proteins, Pavia, Italy 

- june 24, 2006, International Lecture on the “Biology and Pharmacology of Botulinum Neurotoxin” , Merz Foundation, Rostock (Germany)

- jan 26, 2007 Keynote Lecture at the Medical Academy of Turin, Italy 

- feb 28, 2007, Special Seminar on the Mechanism of action of snake presynaptic PLA2 neurotoxins, Istituto Butantan, Sao Paulo, Brazil

- may 4, 2007, Special Seminar on Presynaptic Protein Neurotoxins at the International Center for Genetics and Biotechnology of the United Nations, Trieste

- july 13, 2008, Keynote Lecture at the Gordon Conference on “Microbial Toxins Pathogenicity”, Proctor Academy, Andover, N.H.

- jan 20, 2009 Keynote Lecture at the XV Congress of the Italian Society for Toxicology, Verona, Italy

- march 16, 2009 Redi Lecture at the World Congress of the International Society of Toxinology, Recife, Brazil

- oct 21, 2009 C. Hatheway Lecture amd Medal at the 46th Congress of the Interagency Botulism Research Committees (IBRCC), Alexandria (VA)

- nov 18, 2010, Keynote Lecture at the Congress of the Brasilian Society for the Advancement on Biochemical and Immunological Research, Belo Horizonte, Brazil

- june 18, 2011, EMBO Lecturer at the XV European Congress on Bacterial Toxins, Oslo, Norway

- july, 2011, special Paul-Ehrlich year lecture at the Paul-Ehrlich Institute, Frankfurth

- jan 10, 2013, Special Lecture at the Rome Medical Academy, Rome, Italy

- Keynote Lecture at the "Venoms" Congress, Oxford sept 24-26, 2013

- Plenary Lecture at the Congress of the Italian Society of Toxinology, Milan 2015

 

 

 

  • Duregotti E, Scorzeto M, Negro S, Zornetta I, Dickinson BC, Chang CJ, Montecucco C*, Rigoni M* . Mitochondrial alarmins released by degenerating motor axon terminals activate perisynaptic Schwann cells. Proc Natl Acad Sci U S A. (2015) http://www.pnas.org/content/early/2015/01/15/1417108112.full.pdf 
  • Pirazzini M, Azarnia Tehran D, Zanetti G, Megighian A, Scorzeto M, Fillo S, Shone CC, Binz T, Rossetto O, Lista F, Montecucco C. Thioredoxin and its reductase are present on synaptic vesicles, and their inhibition prevents the paralysis induced by botulinum neurotoxins. Cell Rep. (2014) 8:1870-8. doi: 10.1016/j.celrep.2014.08.017. with highlight in: Montal M. Redox regulation of botulinum neurotoxin toxicity: therapeutic implications. Trends Mol Med. (2014) Sep 18. pii: S1471-4914(14)00142-7. doi: 10.1016/j.molmed.2014.09.005.
  • Rossetto O., Pirazzini M., Montecucco C. Botulinum neurotoxins: recent genetic, structural and mechanistic insights Nat. Rev. Microbiol. (2014)
  • Megighian A, Zordan M, Pantano S, Scorzeto M, Rigoni M, Zanini D, Rossetto O, Montecucco C. Evidence for a radial SNARE super-complex mediating neurotransmitter release at the Drosophila neuromuscular junction. J Cell Sci. (2013) 126:3134-40. 
  • Tonello F., Simonato M.,  Aita A., Pizzo P., Fernández J., Lomonte B., Gutiérrez JM and Montecucco C.. A Lys49-PLA2 Myotoxin of Bothrops asper Triggers a Rapid Death of Macrophages that Involves Autocrine Purinergic Receptor Signaling. (2012) Cell Death & Dis., (2012) 5;3:e343. doi: 10.1038/cddis.2012.68. 

Complete list of pubblications