Aguzzi Adriano

Group Leader

Prof. Dr. med. Dr. sc. h.c. Adriano Aguzzi

 

Name of the Institution

Institute of Neuropathology
UniversityHospital Zürich

Street

Schmelzbergstrasse 12

City

8091 Zürich

Phone

+41-44-255 21 07

E-mail

Group Members

Main Field(s) of Research, Abstract

The main fields of interest are neurodegeneration and the development of cancer in the nervous system.

In the last 10 years we have characterized the neuropathogenic determinants of the human foamy virus using transgenic mice. This was particularly important as it was hoped that the human foamy virus might be useful as a vector for gene therapy. Furthermore, our institute generated the first transgenic model for the development of astrocytic tumors. Astrocytomas develop stochastically upon accumulation of various genetic lesions. One of the current research programs in neurocarcinogenesis uses retroviral tagging to elicit accelerated astrocytomas in transgenic mice. The fundamental aim is to uncover hitherto unknown cooperating oncogenes which may play a role during malignant transformation of astrocytomas, and may be responsible for the remarkable migratory capacity of astrocytoma cells.

The most important topic of research in our institute, however, is the attempt to understand the intricacies of prion neuroinvasion. The latter term defines the process by which infectious prions (the causative agents of BSE and Creutzfeldt-Jakob disease), having entered the body of a victim from an extra-cerebral site, transmigrate into the brain and finally induce disease within the central nervous system. In order to achieve this ambitious goal, a variety of tools of modern biology, such as recombinant adenoviruses and other viral vectors, transgenic and knockout mice, adoptive transfer of haematopoietic cells and a large array of immunological methods are applied. More recently, we have started exploiting the latest tools of functional genomics (high-throughput transcriptional analysis using DNA microarrays, proteomics and representational difference analysis).

The research activities of the Institute of Neuropathology rely on a wide cast network of collaborations. The most important collaborators are Prof. Charles Weissmann (Imperial College, London) and Prof. Rolf Zinkernagel (Institute of Experimental Immunology, Zurich). In addition, Adriano Aguzzi and other faculty members of the Institute are active in networks of the European Union (shared cost actions as well as combined actions aimed at fostering collaboration between European scientists in the field of prion diseases).

Main Fields of Research, Keywords

Prion diseases, transgenic animals

Education and Training

We have training opportunities for Master and PhD students, Postdocs and MD-PhD students.

Selected Publications

Top 14 publications as senior author (only papers published in 2001 or later):

Klein MA, Kaeser PS, Schwarz P, Weyd H, Xenarios I, Zinkernagel RM, Carroll MC, Verbeek JS, Botto M, Walport MJ, Aguzzi A. (2001). Complement facilitates early prion pathogenesis. Nature Medicine 7:488-492.

Heppner FL, Musahl C, Arrighi I, Klein MA, Rulicke T, Oesch B, Zinkernagel RM, Kalinke U, Aguzzi A. (2001). Prevention of Scrapie Pathogenesis by Transgenic Expression of Anti-Prion Protein Antibodies. Science 294:178-182.

Glatzel M, Abela E, Maissen M, Aguzzi A. (2003). Extraneural pathologic prion protein in sporadic Creutzfeldt-Jakob disease. New England J Medicine 349:1812-1820.

Meier P, Genoud N, Prinz M, Maissen M, Rulicke T, Zurbriggen A, Raeber AJ, Aguzzi A. (2003). Soluble dimeric prion protein binds PrP(Sc) in vivo and antagonizes prion disease. Cell 113:49-60.

Prinz M, Heikenwalder M, Junt T, Schwarz P, Glatzel M, Heppner FL, Fu YX, Lipp M, Aguzzi A. (2003). Positioning of follicular dendritic cells within the spleen controls prion neuroinvasion. Nature 425:957-962.

Heikenwalder M, Polymenidou M, Junt T, Sigurdson C, Wagner H, Akira S, Zinkernagel R, Aguzzi A. (2004). Lymphoid follicle destruction and immunosuppression after repeated CpG oligodeoxynucleotide administration. Nature Medicine 10:187-192.

Heppner FL, Greter M, Marino D, Falsig J, Raivich G, Hovelmeyer N, Waisman A, Rulicke T, Prinz M, Priller J, Aguzzi A. (2005). Experimental autoimmune encephalomyelitis repressed by microglial paralysis. Nature Medicine 11:146-152.

Heikenwalder M, Zeller N, Seeger H, Prinz M, Klohn PC, Schwarz P, Ruddle NH, Weissmann C, Aguzzi A. (2005) Chronic lymphocytic inflammation specifies the organ tropism of prions. Science 307:1107-1110.

Seeger H, Heikenwalder M, Zeller N, Kranich J, Schwarz P, Gaspert A, Seifert B, Miele G, Aguzzi A. (2005). Coincident scrapie infection and nephritis lead to urinary prion excretion. Science 310:324-326

Heikenwalder M, Kurrer M.O, Margalith I, Kranich J, Zeller N, Haybaeck J, Polymenidou M, Matter M, Bremer J, Lindquist SL, Aguzzi A (2008). Lymphotoxin-dependent prion replication in inflammatory stromal cells of granulomas. Immunity 29:998-1008.

Wolf MJ, Hoos A, Bauer J, Boettcher S, Knust M, Weber A, Simonavicius N, Schneider C, Lang M, Stürzl M, Croner RS, Konrad A, Manz MG, Moch H, Aguzzi A, van Loo G, Pasparakis M, Prinz M, Borsig L, Heikenwalder M. Endothelial CCR2 Signaling Induced by Colon Carcinoma Cells Enables Extravasation via the JAK2-Stat5 and p38MAPK Pathway. Cancer Cell. 2012 Jul 10;22(1):91-105.

Krautler NJ, Kana V, Kranich J, Tian Y, Perera D, Lemm D, Schwarz P, Armulik A, Browning JL, Tallquist M, Buch T, Oliveira-Martins JB, Zhu C, Hermann M, Wagner U, Brink R, Heikenwalder M, Aguzzi A. Follicular dendritic cells emerge from ubiquitous perivascular precursors. Cell. 2012 Jul 6;150(1):194-206.

Aguzzi A, Falsig J. .Prion propagation, toxicity and degradation. Nat Neurosci. 2012 Jun 26;15(7):936-9. doi: 10.1038/nn.3120.

Sonati T, Reimann RR, Falsig J, Baral PK, O'Connor T, Hornemann S, Yaganoglu S, Li B, Herrmann US, Wieland B, Swayampakula M, Rahman MH, Das D, Kav N, Riek R, Liberski PP, James MN, Aguzzi A.The toxicity of antiprion antibodies is mediated by the flexible tail of the prion protein. Nature. 2013 Jul 31. doi: 10.1038/nature12402.

Important papers as senior author dating from before 2001:

Brandner S, Isenmann S, Raeber A, Fischer M, Sailer A, Kobayashi Y, Marino S, Weissmann C, and Aguzzi A. (1996). Normal host prion protein necessary for scrapie-induced neurotoxicity. Nature 379:339-343.

Blättler T, Brandner S, Raeber A.J, Klein M.A, Voigtländer T, Weissmann C, and Aguzzi A. (1997). PrP-expressing tissue required for transfer of scrapie infectivity from spleen to brain. Nature 389:69-73.

Klein M.A, Frigg R, Flechsig E, Raeber A.J, Kalinke U, Bluethmann H, Bootz F, Suter M, Zinkernagel R.M, and Aguzzi A. (1997). A crucial role for B cells in neuroinvasive scrapie. Nature 390:687-690.

Fischer M.B, Roeckl C, Parizek P, Schwarz H.P, and Aguzzi A. (2000). Binding of disease-associated prion protein to plasminogen. Nature 408:479-483.

Funding

Swiss National Science Foundation, University of Zurich, European Union, KFSP, Federal Office of Health, various industrial sources, private endowments and donations.

URL

Link to "Forschungsdatenbank" of the University

http://www.research-projects.uzh.ch/a141.htm