Projects


Immunotherapy of pancreatic adenocarcinoma

Immune system consists of two co-operating parts, innate and adaptive immunity. We decided to use huge potential of innate immunity (for example 1011 neutrophils are created in humans each day), which acts very fast. Tumors are not protected against innate immunity attack. There is no reason to be protected against this attack as tumor cells are not considered as target of innate immunity. This fact we are changing. We bind to tumor cell surface molecules of mannan, part of the wall of yeast cells. Innate immunity cells focus on tumor cells labelled this way and destroy them. Using so called TLR agonists (part of bacteria and viruses) we attract as much as possible of innate immunity cells in tumor.

 

Serpins from the salivary glands of the tick Ixodes ricinus

Serpins form the largest superfamily of protease inhibitors, and they are ubiquitously distributed in nature including viruses and prokaryotes. With over 6000 members, serpins are the most studied protease inhibitors, also thanks to their unique and highly intriguing mechanism of inhibition and the evolutionary changes that turned inhibitory serpins into non-inhibitory proteins with completely different functions. Arthropod serpins have mostly immunological and hemostatic functions. Serpins have been shown to regulate haemolymph coagulation, are involved in phenoloxidase system activation in insects, and regulate an immune toll pathway in haemolymph. Furthermore, in bloodfeeding arthropods, serpins can act as modulators of host hemostasis and/or immune responses. Indeed, several insect serpins act as anti-coagulants, anti-complement proteins and immunosuppressors. Serpins are abundant in ticks, and one of their functions is to modulate host immune system. Ixodes ricinus expresses around 35 serpins and the majority is secreted, thus probably involved in host immunomodulation. Due to tick effort to evade an overcome hosts’ immune system, also tick serpins most likely contribute to this effort. This can make tick serpins interesting from pharmaceutical point of view as new candidates for drugs development.

 

The effect of tick saliva on cellular stress responses and its implication to tick-borne encephalitis virus transmission

Main project of our laboratory is aimed to the analysis of cellular stress pathways induced upon infection by tick-borne encephalitis virus in skin resident cells. We hypothesize that tick saliva and tick salivary components by influencing host cellular stress responses could affect the function of immune cells and consequently pathogen transmission and spreading to host. In TBEV infected dendritic cells and macrophages we determine oxidative stress responses and unfolded protein responses (as reaction to stress on endoplasmic reticulum). We pay attention to processes like apoptosis and autophagy which are often initiated in stressed cells. And finally, as signals called DAMPS (danger associated molecular pattern) are crucial for triggering of adequate immune reaction, interference of tick saliva with DAMPs signaling is currently examined as well.