E-mail: Edwin Tijhaar
Research interests: Veterinary Immunology
Developing tools for cytokine research in Veterinary Immunology
Cytokines play a crucial role in the communication between the cells of the immune system. For humans and mice many cytokine “tools”, like specific antibodies, recombinant cytokines and detection tests, are available.Unfortunately, these kind of reagents are hardly available for species of veterinary interest, which hampers the development of the field of Veterinary Immunology. We are therefore developing the most important of these cytokine tools for the species that are/will be studied within the Cell Biology and Immunology group, i.e. carp, cows, dogs and horses. These tools will contribute to a better understanding of the immune system of these animals and are also important for applied research in the fields of immunopathology (i.e. allergy), tumour immunology and vaccine development. Within this project students can learn a lot of techniques: cloning and expression of (cytokine) genes, purification and refolding of recombinant proteins, SDS-PAGE, Western blotting, production and purification of monoclonal and polyclonal antibodies, cellular assays and the development of sensitive detection test (capture Elisa’s).
Biomarkers and immune modulators of natural resistance of dairy cows
This project aims to identify biomarkers indicative for the immune status or “natural resistance” of dairy cows and to identify (management) factors that influence this natural resistance (= immune modulators). The biomarkers will be measured in milk and blood samples and their levels will be related to the disease susceptibility of the cows. It will also be determined how changes in management factors, aimed at increasing the natural resistance of the dairy cows, affects the levels of these biomarkers. This project should finally result in a test kit for biomarkers to determine in an objective way the “natural resistance” status of a dairy cow and a list of management tools that can be used to improve this natural resistance.
Cancer immunotherapy in dogs by tumor infiltrating Salmonella bacteria
Some attenuated Salmonella strains have the ability to grow preferentially in tumor tissue. This has an inhibiting effect on tumor growth and can even induce complete regression of established tumors in mice. Three mechanisms have been identified that are responsible for this anti-tumor effect of Salmonella typhimurium in mice:
- S. typhimurium infected malignant cells are recognized and killed by anti-. S. typhimurium specific cytotoxic T cells.
- a massive recruitment of effector cells (both innate and adaptive immune cells) is induced at the site of infection.
- infection by S. typhimurium induces the cross-presentation of tumor antigens and the establishment of systemic anti-tumor responses.
At CBI several strategies are used to potentiate the anti-tumor immunity induced by attenuated S. typhimurium strains. Initially these strategies will be tested in a tumor model in mice. The most successful strategy will then be tested on dogs with spontaneous tumors (canine patients). This is of considerable veterinary interest, as approximately 30% of dogs develop cancer and their treatment options are currently limited. If successful, this canine study can also pave the way to clinical trials in humans, as the dog may offer a more realistic pre-clinical model than the mouse.