Understanding the role of complement regulation in chronic inflammatory conditions
Alternative pathway dysregulation is a central event in development of certain diseases caused by mutations or polymorphisms in complement regulator factor H (FH). While mutations in the C-terminal domains of FH are associated with atypical hemolytic uremic syndrome (aHUS) the Y402H polymorphism in domain 7 is associated with age-related macular degeneration (AMD).
We have shown that FH interacts with apolipoprotein E (apoE) via domain 7 and thereby reduces complement activation on plasma HDL particles. This project aims to understand the role of FH-apoE interaction in chronic inflammatory diseases, such as atherosclerosis and Alzheimer's disease.
Streptococci: host susceptibility to inflammation and infections
Diseases caused by Pneumococcus, Group A and G beta hemolytic streptococci are common in humans. The disease spectrum is wide, and some of the disease manifestations, such as erysipelas, may reoccur. Host susceptibility to streptococcal disease varies, which may be due to characteristics of the bacterium or genetic or immunological susceptibility of the host.
In our studies, we aim to understand the role of microbial virulence factors in the invasiveness of the bacterial strain and in inducing chronic inflammation in age-related diseases such as atherosclerosis and Alzheimer's disease. In this work, we utilize sequencing, mass spectrometry and wide array of bioinformatics tools.
Target discrimination by complement factor H in pathogenesis of human diseases
Complement is an important arm of innate immunity consisting of a group of plasma and cell surface proteins. To target this defense mechanism right the essential regulator of the alternative pathway of complement, FH, needs to prevent activation on host cells while allowing it on microbes.
Inability of FH to discriminate between own and foreign surfaces leads to aHUS characterized by destruction of host's own cells. We have previously shown that microbial molecules can modify self surfaces sensitizing our cells to complement mediated attack.
This project aims to solve open questions in pathogenesis of aHUS, and especially those cases where infections or anti-FH autoantibodies cause the disease, and to reveal the similarities and differences in binding of FH to surfaces of pathogenic microbes and host surfaces. The project might lead to finding of new treatment options for aHUS or infections caused by different microbes.