Prof. Dr. Adriano Aguzzi

 

Main Goals, Keywords

• Discovery of pathogenetic mechanisms involved in neurodegenerative diseases. As a disease model, we chose to use scrapie, a prion disease affecting sheep which has been transmitted to mice.
• Pathogenesis of tumor progression in astrocytomas. Transgenic and knock-out mice, as well as neuroectodermal grafts, are being used to discover molecules and pathogenetics principles which control disease progression in human brain tumors.

Group Members

1 professor, 1 attending physician, 2 senior research associates, 5 postdoctoral fellows, 4 medical doctoral students, 4 PhD students, 2 diploma students, 3 technicians

Previous and Current Research

Our scientific activities focus on two areas which are well-distingued from each other – however, similar model systems and methodologies are being used in both areas. One focus of our research activity is the investigation of the pathogenetic events which lead to the neuroinvasion of prions in the body of infected individuals (Fig. 1). To this end, we are using a large array of methodologies including transgenic and knock-out mice, recombinant adenoviruses, brain grafts (Fig. 2) and adoptive transfer of haematopoetic cells. Our work in the last five years has been carried out in the frame of a close collaboration with the group of Charles Weissmann (Institute of Molecular Biology, University of Zürich) and of Rolf M. Zinkernagel (Institute of Experimental Immunology, University of Zurich).

The other long-standing research project concerns the histogenesis and progression of human malignant brain tumors. Here we have developed a transgenic mouse model for the progression of astrocytomas. In these mice which express a GFAP-v-src transgene, astrocytomas develop stochastically suggesting the cooperation of further genetic lesions. By random mutagenesis through retroviral tagging, we are currently trying to accelerate the induction of neoplastic legions, in order to identify further, hitherto unknown oncogenes which may play a role in the malignant progression of experimental, and hopefully also human, astrocytomas.

Techniques and Equipment

We are using a variety of transgenic and knock-out mouse models, combined with neurosurgical technologies such as transplantation of embryonal neuroectodermal tissue into brain and spinal cord, as well as delivery of viral vectors to neural structures (such as dorsal root ganglia).

Selected Publications

• Calella, A.M., Farinelli, M., Nuvolone, M., Mirante, O., Moos, R., Falsig, J., Mansuy, I.M., Aguzzi, A. Prion protein and Abeta-related synaptic toxicity impairment. EMBO Mol Med. Aug. 2(8): 306-14 (2010).
• Kranich, J., Krautler, N.J., Falsig, J., Ballmer, B., Li, S., Hutter, G., Schwarz, P., Moos, R., Julius, C., Miele, G., Aguzzi, A. Engulfment of cerebral apoptotic bodies controls the course of prion disease in a mouse strain-dependent manner. J Exp Med. Sep 27; 207(10): 2271-81. Epub Sep 13 (2010).
• Aguzzi, A., Steele, A.D. Prion topology and toxicity. Cell. Jun 12; 137(6): 994-6 (2009).
  

Selected Lectures, Seminars, Colloquia

• 428 Molekulare Grundlagen neurologischer Erkrankungen (Progress report)
• 707 Aktuelle Probleme der Krankheitsforschung
• 798 Neurorama - interdisziplinäre Veranstaltung des klinischen Neurozentrums alternierend mit dem Oto-neuro-ophtalmologischen Kolloquium

Academic positions in my lab

Advice to applicants for master, PhD and postdoc positions (pdf, 58 KB)

Funding

Swiss National Science Foundation, EU Biomed Programme, Swiss Research Programme on Neurodegenerative Diseases (NFP-38), Federal Office of Health, Federal Office of Veterinary Medicine, various biotech companies