Regulation of the complement system in health and disease
Principal investigator; Blom, Anna, Professor, PhD
Co-workers: Myriam Martin, postdoc; Marcin Okroj, postdoc; Sven Malm, postdoc; Vaibhav Agarwal, postdoc; Nikolina Kalchishkova, postdoc; Jose Gallego, postdoc, Izabela Nita, postdoc, Ben King, postdoc
The aim of our study is to gain more knowledge about regulation of human complement system. Proper activation of complement is crucial for defense against pathogens and development of immunity whereas excessive activation is involved in pathogenesis of many diseases. So far there is no complement inhibitor that can be used in a clinical setting and detailed knowledge of the system is required for development of such inhibitor. Furthermore, many pathogens bind human complement inhibitors by which they are becoming protected from complement attack. Knowledge about how this happens may be used in therapy of the corresponding infectious diseases.
We want to investigate in detail C4b-binding protein (C4BP), an important inhibitor of complement: structural requirements for functional activity, interactions with several microbial pathogens and tumor cells, polymorphisms leading to deficiency, as well as possibility that C4BP localized to apoptotic (dying) cells inhibits complement activation on their surface and allows for them to be removed without evoking inflammation. We also want to study structure, function and genetic basis for deficiencies of proteinase Factor I to which C4BP is a cofactor. Furthermore, we will search for new human complement inhibitors as well as inhibitors produced by human pathogens and then study their function and structure. Finally we investigate which molecules that are responsible for pathologic activation of complement in joints. Yet another investigated subject is how do the cancer cells protect themselves from eradication from complement system.
Our studies lead to better understanding of regulation of complement system, which is a prerequisite in development of modulating therapy.
Studies of various strategies developed by pathogens in order to avoid complement attack may aid in vaccine development. We are also working towards creating a complement inhibitor to be used in treatment of number of inflammatory diseases.
Link to project homepage: http://www.demesta.com/annablomresearch
5 recent original publications
Ram S., Cullinane M., Blom A. M., Gulati S., McQuillen D. P., Monks B. G., O Connell C., Boden R., Elkins Ch., Pangburn M. K., Dahlback B. and Rice P. A.
Binding of C4b-bidning protein to porin: A molecular mechanism of serum resistance of Neisseria gonorrhoeae.
Journal of Experimental Medicine. 2001; 193: 281-295
Blom A. M., Kask L. and B. Dahlbäck
Structural requirements for the complement regulatory activities of C4-binding protein.
Journal of Biological Chemistry. 2001; 276: 27136-27144
Spiller B. O., Blackbourne, D., Mark L, Proctor D. and Blom A. M.
Functional activity of the complement regulator encoded by Kaposis´s sarcoma associated herpesvirus.
Journal of Biological Chemistry. 2003; 278: 9283-9289
Happonen Kaisa, Saxne Tore, Aspberg Anders, Mörgelin Matthias, Heinegård Dick, Blom Anna
Regulation of complement by COMP allows for a novel molecular diagnostic principle in rheumatoid arthritis.
Arthritis and rheumatism. 2010; Aug 24: -
Trouw L., Nilsson S., Goncalvez I., Landberg G. and Blom A. M.
C4b-binding protein binds to necrotic cells and DNA, which limits DNA release and inhibits complement activation.
J Exp Med. 2005; 201: 1937-1948
Further publications here (new window)
|Total financing:||8.0 MSEK||Gov grant for clinical research ("ALF"):||2.0 MSEK|
|Total external financing:||5.0 MSEK||Natl and intl prioritized grants:||3.0 MSEK|