PD Dr. Scharl Michael

Main Field of Research
The pathogenesis of inflammatory bowel disease, representing a chronic intestinal inflammation, is still poorly understood. Recent evidence suggest that polymorphisms in about 150 susceptibility genes contribute to an aberrant immune reponse 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 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.

Main Fields of Research, Keywords
Inflammatory bowel disease, colorectal carcinoma, protein tyrosine phosphatases, fistulae, T-cells, innate immunity, inflammasome, autophagy

Special Techniques and Equipment
All standard techniques of molecular and cellular biology. Mouse models of colitis and colorectal carcinoma. Isolation of primary human and mouse cells.

Education and Training
PhD training, regular group meetings and journal clubs.