Stefan Rüdiger is Professor for Protein Chemistry of Disease. The Chair Protein Chemistry of Disease is dedicated to gather mechanistic insights into protein folding and cellular protein quality control, and to apply this knowledge to protein-folding related diseases. Fatal diseases associated with protein misfolding include neurodegeneration, cancer or metabolic diseases. Rüdiger's team aims to develop novel, mechanism-based strategies to target currently incurable diseases caused by protein misfolding, including Alzheimers disease and Huntington’s disease. Recent work provided a mechanism of action for the key chaperone systems Hsp70 and Hsp90. The Rüdiger group now focusses to understand how these chaperones control protein aggregation in neurodegenerative diseases. A key finding of his group decribed a structural model of the Hsp90 chaperone in complex with the Alzheimer protein Tau. Based on these findings, the team aims to develop biologics drug leads targeting toxic protein aggregation in the earliest stages.

A key challenge in molecular medicine is to develop cures for diseases for which no cure exists – such as Alzheimer, Parkinson, Huntington or ALS, but also many other diseases with dramatic impact for the affected individual such as ataxias or cystic fibrosis. These diseases have in common that the molecular cause is related to uncontrolled consequences of protein damage and aggregation. Our body is not unprotected against protein damage. The fidelity of protein shape in the cell is maintained by a powerful protein quality control network, in which molecular chaperones and proteases play a key role. This networks supresses the appearance of most folding related diseases for the best part of our life. However, why does it suddently fail when we get older? Why do some individuals get a protein-aggregation related disease and others do not? What is the impact of the protein quality network for the development of an entire organism? Can we boost the cellular defense system to prevent the origin of the disease, or at least prevent progress of the diseases for some cases? How can we exploit our molecular understanding of our knowledge to develop taylor-made compounds to target protein aggregation diseases, including Alzheimer or Huntington?

Rüdiger's group aims to understand protein folding processes in the cell and their consequence for the origin of fatal diseases, and to exploit this knowledge for the development of novel strategies for treatment of these diseases.

Manuscript Inaugural lecture (Oratie) "Art and Destiny", 2 Oct 2023:
R602 Oratio Rüdiger public 231112 1445h.pdf

Current and previous external research support

Alzheimer Nederland (main applicant)
Major grant

Campagne Team Huntington (main applicant)
Full research grant

NWO - Nederlands Organisation for Scientific Research (PI):
ZonMW TOP Grant "Chaperoning axonal transport in neurodegenerative disease"

ISAO  - Internationale Stichting Alzheimer Onderzoek (Main applicant)
https://www.alzheimer.nl/onderzoek/onderzoeksprojecten/chaperonnes-en-de-aggregatie-van-tau/detail

Marie-Curie ITN "WntsApp" (PI)
http://wntsapp.eu/projects/control%20of%20complex%20assembly%20in%20the%20WNT%20cascade
http://wntsapp.eu/projects/chaperone%20binding%20motifs%20in%20disordered%20WNT%20signalling%20proteins

Marie-Curie ITN-IDP "ManiFold" (Programme Leader and PI)
http://www.manifold-idp.nl/CHAPERONE%20BINDING%20MOTIFS%20IN%20DISORDERED%20PROTEINS
http://www.manifold-idp.nl/THE%20SUBSTRATE%20RECOGNITION%20SITE%20OF%20A%20CHAPERONE%20MACHINE

NWO Graduate Programme (Programme Leader)

NWO BAZIS equipment grant (Project Leader)

NWO VIDI grant (Main applicant)

Marie-Curie Excellence Grant (Main applicant)

Utrecht University High Potential Grant (Main applicant, joint grant with Dr Madelon Maurice, UMCU)

Current group members
Júlia Aragonés Pedrola
Franoise Dekker
Magdalena Wawrzyniuk
Iris Rots
Adriana Poza Rodriguez

• News report: students publish scientific paper
• News report: Hsp90 binds to Alzheimer protein Tau
• News report: Marie-Curie movie (report in Dutch, movie in English)
• News report: First practicum in new building!
• https://www.uu.nl/en/news/chaperones-just-prepare-proteins-for-folding-on-their-own-0
• Stefan Rüdiger appointed as Chair Protein Chemistry of Disease