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Be up to date! Have a look at our most recent news.
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.
On October 3rd, Frerich successfully defended his doctoral dissertation in Utrecht. His thesis provided valuable insights into how Gram-negative bacteria escape killing via the complement system.
Frerich’s research comprised of four studies:
The findings highlight the complexity of bacterial immune evasion and the potential for targeting these resistance pathways in the development of new antimicrobial strategies.
We are delighted to congratulate Max on successfully completing his PhD! His thesis provided valuable insights into the role of the complement system in the innate immune response, focusing on the pathogens SARS-CoV-2 and Aspergillus fumigatus.
Max's research comprised three significant studies:
(1) Max developed a sensitive MASP-2 ELISA to investigate its association with COVID-19. He found that MASP-2 concentrations were significantly increased in COVID-19 patients compared to healthy controls and correlated with age, female sex, and higher mortality. Additionally, MASP-2 levels were linked with terminal complement complex (TCC), ficolin-2, ficolin-3, and C-reactive protein (CRP), suggesting MASP-2 as a potential biomarker for COVID-19.
(2) By exploring the binding kinetics of pattern recognition molecules (PRMs) of the complement system on pathogen surfaces, Max discovered that C1q and MBL rapidly bound and then detached from pathogen surfaces within minutes in plasma, a process associated with complement cascade activation. C1q detachment was linked to the activation of the C1 complex, while MBL dissociation relied on overall complement activation and solubilization via C3b.
(3) Max investigated the innate immune responses to A. fumigatus in whole blood, finding that it triggered complement and leukocyte activation, similar to E. coli. Although A. fumigatus induced a less extensive cytokine response compared to E. coli, complement inhibition significantly altered the release of six key cytokines, indicating the complement system's role in cytokine release. The expression of most cytokines depended on the monocyte fraction in whole blood.
Collectively, these studies demonstrate the significant role of the complement system in infections with SARS-CoV-2 and A. fumigatus. Max's work highlights the potential connections between cytokine release, pathogen opsonization, and the detachment of C1q and MBL from microorganisms, though further research is needed to fully understand these mechanisms.
We wish Max the best of luck for his future academic career.
We are thrilled to announce that Beatrice has successfully graduated with her PhD! Her thesis explored the human innate immune system using the lepirudin whole blood model. This model, introduced in 2002, uses the anticoagulant lepirudin to maintain complement system function while preventing blood coagulation. Beatrice's work involved collecting blood in lepirudin-treated tubes, exposing it to various activators, and analyzing cell activation markers, complement activation, and inflammatory mediators.
Beatrice's thesis consisted of three significant papers:
Paper I: Beatrice developed a novel model by selectively removing individual cell populations, revealing the specific roles of monocytes and granulocytes in cytokine release. This study was published in the Journal of Leukocyte Biology.
Paper II: She investigated the inflammatory response to Aspergillus fumigatus conidia compared to Escherichia coli, identifying CD14+ monocytes as key contributors to cytokine release. This paper was published in the Journal of Innate Immunity.
Paper III: Beatrice adapted the model to study patients with acute myelogenic leukemia (AML) undergoing hematopoietic stem cell transplant (HSCT). The study showed that AML patients maintain a functional complement system throughout the transplantation period. This paper is under revision for publication in Frontiers in Immunology.
Collectively, these papers enhance our understanding of innate immune responses and pave the way for new targeted therapeutic strategies.
We are incredibly proud of Beatrice's achievements and wish her all the best in her scientific career.
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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.
