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Be up to date! Have a look at our most recent news.
On the 11th June 2024 two CORVOS ESRs Hang Zhong (IT-1) and Mikel Rezola Artero (FI-2) participated in the 16th International Conference on Complement Therapeutics. They showcased their research through oral presentations and flash poster talk sessions which stimulated scientific discussion and provided invaluable feedback on both projects.
This meeting in Loutraki, Greece, provided an opportunity to bring together complement experts from both academia and industry. Participants shared new data and discussed the latest developments in therapeutic design, clinical trials, and new aspects of complement-driven pathophysiology.
Following an intense, one week program on a wide variety of topics ranging from complement-driven haematological/ocular/kidney/neurological disorders to complement in infectious diseases, the conference finished with a farewell dinner where all the participants enjoyed live music and had the opportunity to learn some local dances. Finally, the evening culminated in the announcement of the awards, where both of the ESRs received trainee awards due to their commendable contributions to the conference.
We are delighted to announce that Mariam has successfully completed her PhD! Her research focused on the complement system, specifically the component C7, which is crucial for the assembly of the membrane attack complex (MAC). While the structure and function of C7 in MAC assembly are well documented, Mariam's work aimed to uncover the non-canonical roles of C7, which are less understood. Mariam's thesis explored several key areas: (1) Extrahepatic Synthesis of C7: Unlike most complement proteins, C7 is primarily synthesized outside the liver, allowing it to regulate local MAC assembly. This unique synthesis pathway suggests that C7 could play distinct roles in different tissues. (2) Association with Disease Pathogenesis: Emerging studies have linked C7 with various diseases, highlighting the need for further investigation into its non-canonical functions. (3) Development of Monoclonal Antibodies (mAbs) and Immunoassays: A major aim of Mariam's research was to create reliable tools for characterizing C7. She developed monoclonal antibodies that specifically bind to native C7, which were then used to establish an enzyme-linked immunosorbent assay (ELISA) for measuring C7 in different matrices. This novel ELISA demonstrated high specificity and no cross-reactivity with similar proteins. (4) Interaction with Clusterin (CLU): Mariam's investigation into the regulatory role of C7 revealed a significant association with the complement inhibitor clusterin (CLU). Her work indicated the presence of a C7-CLU complex in circulation, suggesting that C7 has multifunctional roles beyond its traditional functions in MAC assembly.
Mariam's innovative research has provided new insights into the complex roles of C7 and developed valuable tools for future studies. We are incredibly proud of her accomplishments and wish her all the best in her scientific career.
The International Complement Workshop in Newcastle, organized by Kevin Marchbank and Claire Harris and their team was the first complement meeting in person of the International Complement Society to be organised after the Corona crisis. In Berlin 2021, it was quite funny to chase people virtually in poster viewing rooms and it was great to hear good science and to keep contact, but it is simply not the same thing to meet in person. Thus, a lot of CORVOS housekeeping issues were discussed in person, including an official CORVOS Supervisory Board Meeting, organised by the CORVOS & HOROS administrator Silke Huber.
Now, after so many students being quite advanced, the networking in the evening in the bars was a highlight. The CORVOS students met for a dinner with their supervisors.
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The European Meeting on Complement in Human Disease, Lübeck, 2024, organized by Jörg Köhl and his team was the official international farewell event for CORVOS with a concluding meeting meeting.
The final report had been accepted well before and the speaker, Reinhard Würzner, was proud to announce that all projects were successfully accomplished (due to the Corona crisis some had to be changed, though, but most actually to the better and a lot of CoCo papers (for Complement & Corona) were published by the CORVOS consortium). After the meeting the consortium met at the Schiffergesellschaft where the Speaker delivered some final words and the CORVOS aprons in the courtyard. The dinner was afterwards in the very picturesque halls.
Time to say goodbye to some members of the consortium, but others were looking forward to another Obergurgl retreat in early January 2025. Thus, CORVOS is still flying....
Together, these three studies form a cohesive body of work that significantly advances our understanding of the complement system in various clinical contexts. The novel antibody targeting C5aR1 offers a promising therapeutic tool, while the stem cell transplantation study challenges our understanding of immune dynamics during transplantation. Finally, the exploration of complement modulation in whole blood emphasizes the potential of complement-targeted therapies in infectious diseases.
The successful defense marks the culmination of years of rigorous research and sets the stage for further advancements in the field. As the research moves forward, it holds promise for better therapeutic strategies for autoimmune diseases, transplantation, and infectious diseases.
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We are happy to share that Julia successfully defended her PhD in Paris on December 18th, 2024. Her doctoral dissertation focussed on acquired abnormalities in complement-mediated glomerulonephritis, and highlighted three studies :
Study I: Functional characterization of anti-C3bBb autoantibodies and C3 Glomerulopathy phenotype. Julia has developed new biochemical assays to identify IgG autoantibodies targeting the C3BbB convertase, and found association of autoantibodies function with the complement alternative pathway overactivation and the disease severity of C3 Glomerulopathy.
Study 2: Spectrum of anti-factor B associated glomerular diseases in adults. Julia highlighted that anti-Factor B was strongly associated with infection-associated glomerulonephritis. The functional characterization of these autoantibodies highlighted the proconvertase C3bB formation and the C3bBb stabilization as two important mechanisms of alternative pathway dysregulation.
Overall this work provides new pieces in our understanding of the pathophysiology of complement-mediated glomerulopathies but also paves the way for the use of new diagnostic assays for C3bBb convertase targeting autoantibodies and complement-targeted therapies to improve patient outcomes.
On a cold December day in Helsinki, the 13th December 2024, Mikel Rezola Artero defended his PhD successfully to gain a PhD from University of Helsinki and University Sorbonne in Paris. In his thesis, entitled “Mechanisms of complement subversion in Infection and cancer” he compared the evasion strategies pathogens and tumour cells employ to evade the complement system.
On the pathogen side, he explored how P. falciparum sporozoites resist complement attack through hijacking of the complement regulator C4b binding protein (C4bp).
On the tumour side, he investigated the mechanism behind the pro-tumoural role of intracellular factor H (FH) by a combination of transcriptomics in patient tumours, cellular and biochemical assays that demonstrated that intracellular FH acts as a multitasking tumour-promoting effector by regulating cell cycle progression and by maintaining cytoskeleton organization.
Thus both pathogens and tumour cells employ different, but on the other hand, similar mechanisms.
Ruben Pio Oses, Navarra, Spain, who was also a referee of the thesis earlier, acted as opponent. The other referee, and speaker of CORVOS, Reinhard Würzner, Innsbruck, Austria, was also in the evaluation committee on site. The two supervisors, Seppo Meri, Helsinki, Finland and Loubka Roumenina, Sorbonne, Paris, France were also present. The evening before, the candidate and the invited guests met at a typical Karelian restaurant and after the defence in the prestigious and picturesque Villa Aikala with a Lebanese buffet.
Congratulations to Mikel for his remarkable accomplishment!
We are pleased to announce that Michal successfully defended his PhD thesis on October 25, 2024. His work focused on the complement evasion mechanisms developed by human pathogens, mainly Acinetobacter baumannii, Klebsiella pneumoniae, and Streptococcus pyogenes.
Papers I and II were dedicated to A. baumannii, a worrisome complement and antibiotic-resistant pathogen. In these papers, Michal screened many isolates from the genus Acinetobacter and aimed to characterize their MAC evasion strategy. He found two potential mechanisms worthy of further investigation.
In paper III, the focus switched to K. pneumoniae, another serious human pathogen. This study highlighted a surprising connection between complement and colistin resistance in isolates obtained from patients. This study delivered results worth considering in the epidemiology of Klebsiella infections.
Paper IV aimed to provide a treatment option that counteracts the complement evasion mechanism in S. pyogenes. This bacterium acquires the complement inhibitor factor H from serum to evade opsonization. Replacing the serum-bound inhibitor with the FH6-7/hFc fusion protein increased complement activation and resulted in better animal survival in the mouse model. This protein highlighted the possibility of using bacterial evasion mechanisms against the bacteria themselves.
Taken together, Michal's findings gave us a better overview of bacterial infections and their complement evasion mechanisms. As antibiotic resistance among human pathogens becomes more serious, novel treatment options are needed.
We wish Michal all the best for his future career and research projects.
