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Wilhelm Schwaeble

The role of complement in health and disease

For over 30 years, I have been fortunate enough to deliver key contributions towards our understanding of the organization and molecular composition of the innate immune response. My research activities comprise molecular biology, gene regulation, protein biosynthesis, structural biology, structure/function relations, measurements of functional activities, systems cross-talk, establishment of gene-targeted and transgenic mouse lines and their phenotypic characterisation in experimental models of disease. One of my key achievements over the recent years was my part in the discovery of a novel activation pathway of complement, now known as the lectin pathway. My work has led to the discovery of pathophysiological processes driven and maintained by dysregulation of this specific activation pathway linked to a plethora of chronic inflammatory human and animal diseases. This work was made possible through major funding support from both the MRC and the WELLCOME TRUST at programme grant level. My collaborations with an industrial partner, OMEROS Corporation, Seattle, USA has lead to the development of novel therapeutic approaches for the treatment of severe inflammatory pathologies caused by uncontrolled activation of the humoral innate immune response. I feel privileged to see that parts of my work have lead to the production of novel tools and therapeutic concepts which have shown high therapeutic efficacy with an excellent safety profile in on-going clinical trails. My present work programmes are part of an international network of collaborations with academic institutions all over the world aiming to understand the contributions of complement activation in various disease processes.


 

Key Publications

Schwaeble, W.J.; Lynch, N.J.; Clark, J.; Marber, M.; Samani, N.J.; Ali, M.Y.; Dudler, T.; Parent, B.; Lhotta, K.; Wallis, R.; Farrar, A.; Sacks, S.; Lee, H.; Zhang. M.; Iwaki, D.; Takahashi, M., Fujita, T.; Tedford, C.E.; Stover, C.M. Targeting of Masp2 confers a significant degree of protection from myocardial and gastro-intestinal ischemia/reperfusion injury. Proc.Natl.Acad.Sci. USA 108:7523-7528 (2011)

Ali, Y.M.; Lynch, N.J.; Haleem K.S.; Kadioglu, A.; Fujita, T.; Endo, Y.; Hansen, S.; Holmskov, U.; Takahashi,K.; Stahl, G.L.; Dudler, T.; Girija, U.V.; Wallis, R.;  Stover, C.M.; Andrew, P.W.; Schwaeble,W.J. The Lectin Pathway of Complement Activation is a Critical Component of the Innate Immune Response to Pneumococcal Infection. PLOS Pathog. 8: e1002793. (2012)

Ali, Y.M.; Hayat, A.; Mawlood,B.; Haleem, K.S.; Alshamrani, S.; Kenawy, H.; Ferreira, V.P.; Gurpanna Saggu, G.; Buchberger, A.; Lachmann, P.J.; Sim, R.B.; Goundis, D.; Andrew, P.W.;Lynch, N.J.; Schwaeble W.J. Low dose recombinant properdin provides substantial protection against Streptococcus pneumoniae and Neisseria meningitidis infection. Proc.Natl.Acad.Sci U.S.A. 111:5301-5306 (2014) Apr 8. [Epub ahead of print]

Orsini,F.; Chrysanthou, E.; Dudler, T.; Cummunigs, W. J.; Takahashi, M.; Fujita, T.; Demopulos, G.; De Simoni, M.-G.; Schwaeble, W.J. Mannan Binding Lectin-Associated Serine Protease-2 (MASP-2) critically contributes to post-ischemic brain injury independent of MASP-1. J. Neuroinflamm. 13: 213-226 (2016). doi: 10.1186/s12974-016-0684-6.

Yaseen,S.; Demopulos, G.; Dudler, T.; Yabuki, M.; Wood, C.L.; Cummunigs, W.J.; Tjoelker, L.W.; Fujita, T.; Sacks, S.; Garred, P.; Andrew, P-W. Lachmann, P.J.; Wallis, R.; Lynch, N.J. Schwaeble, W.J. Lectin pathway effector enzyme mannan-binding lectin-associated serine protease-2 can activate native complement C3 in absence of C4 and/or C2. FASEB J. 31: 2210–2219 (2017) Feb. 10 (2017). doi: 10.1096/fj.201601306R

Hans Wilhelm Schwaeble

Dr Wilhelm Schwaeble

Director of Research

Plain English

The immune system is a double-edged sword that on one hand protects us from infectious disease and on the other hand can contribute to inflammatory pathologies, if insufficiently controlled.

My work aims to further the understanding of the roles of specific components of an immune defence system called complement in fighting infection as well as their possible contributions towards non-infectious inflammatory processes that may lead to severe morbidity and mortality.

The development of recombinant activators or inhibitors of key components of the complement system has provided us with the tools to explore the clinical utility of desperately needed novel therapies to improve the clinical outcome of infectious and inflammatory human and animal disease.

Funding