The role for protein tyrosine phosphatases and epithelial-to-mesenchymal transition in the pathogenesis of inflammatory bowel disease and colorectal carcinoma.
University of Zurich
1 or 2 semesters
The pathogenesis of inflammatory bowel disease, representing a chronic intestinal inflammation, is still poorly understood. Recent evidence suggest that polymorphisms in more than 160 susceptibility genes contribute to an aberrant immune response to food allergens, microbial components and environmental toxins finally resulting in an impaired intestinal barrier function and excessive cytokine secretion. As a consequence, chronic inflammation is established and major complications, such as the development of intestinal fistulae or colorectal carcinoma occurs. Protein tyrosine phosphatases play a key role for modulating pro-inflammatory signal transduction and cytokine secretion, controlling the adaptive and innate immune system as well as regulating cell growth and cell proliferation. Further, they have been implicated in a variety of malignant tumors. In our laboratory, we investigate the role for certain protein tyrosine phosphatases, such as PTPN2, PTPN9, PTPN22 and PTPN23 in the pathogenesis of chronic intestinal inflammation as well as of colorectal carcinoma. Further, we are studying the pathogenesis of Crohn’s disease associated fistulae that feature epithelial-to-mesenchymal transition (EMT) as a characteristic pathogenetic mechanism. However, the molecular mechanisms underlying the onset of these fistulae are still poorly understood. So far, we could demonstrate that pro-inflammatory cytokines as well as bacterial antigens critically contribute to development of EMT in the intestinal tract and therefore to the pathogenesis of Crohn’s disease associated fistulae. Since EMT is also associated with the onset of colorectal carcinoma, a further goal of our laboratory is to investigate the pathogenesis of colorectal carcinoma. In this subject, we are studying the role for certain protein tyrosine phosphatases as well as of alpha v beta 6 integrin.
The project runs from 1 May 2015 - 31 December 2018 and is open for recently graduated undergraduate students and for graduate students.
The project is available in the Fall and Spring semesters.
Number of places available: 2 per semester.
- The applicants should have sufficient abilities in basic reserach and be able to cooperate with a number of international people.
- Further, they should be interested in perfoming cell culture experiments, mouse experiments as well as working with human tissue samples.
Faculty of Medicine.
The Division of Gastroenterology and hepatology at the University Hospital Zürich is part of the University of Zurich. The UZH provides an excellent environment for this project. The University of Zurich is one of the leading universities in Europe and the world. The medical faculty of the University of Zurich is the largest in Switzerland. It represents one of the leading biomedical research centers in the world. Research of the highest international standard, both basic and clinical, is carried out here. There are intensive collaborations with research groups of leading universities and with scientific research centers all around the world. The medical faculty has set up joint centers of excellence with other faculties in the University and at the ETH Zurich, so as to promote research in interdisciplinary fields of potential future importance. A number of biotech companies in the area provide immense opportunities for research. Important focuses of research are molecular medicine, immunology, neuro-sciences and cardiovascular diseases. At the University Hospital of Zurich a Center of Clinical Research has been implemented coordinating the efforts to improve clinic-based research. The applicant is a member of the Center of Integrative Human Physiology (ZIHP) supporting research collaborations between basic research and clinical research, translational research programs and a very structured PhD training program (graduate school).