Microvilli in intestinal barrier function, colitis and colon cancer
The intestinal barrier function is maintained through multiple mechanisms, including the production of mucus, antibacterial peptides, and a tight sealing between gut epithelial cells. The latter are covered by the brush border, which consists of densely packed cellular extrusions called microvilli.
We believe that microvilli represent an important barrier to cellular entry of bacteria. We investigate functions of the protocadherin CDHR5, which crosslinks microvilli and is required for regular microvillus organization.
We use CDHR5-deficient mice with disorganized microvilli to study the role of the brush border in bacterial penetration, inflammation, and colon carcinogenesis.
Cytokine signaling in colon cancer development
Inflammation of the gut leads to the production of various cytokines that activate cytokine receptors on gut epithelial cells, mesenchymal cells and all types of immune cells.
The Janus kinase TYK2 and the transcription factors STAT1 and STAT3 are located downstream of these cytokine receptors and are considered to mediate tumor-promoting and tumor-preventive effects in colon carcinogenesis.
We have shown that inhibition of STAT3 in myeloid cells or STAT1 in epithelial cells prevents colon cancer development through immune-mediated mechanisms (Pathria et al., OncoImmunology 2015; Pflügler et al., Communications Biology 2020).
We are currently investigating the role of TYK2 and the interplay between STAT1 and STAT3 in myeloid cells in immune-mediated cancer cell killing.
Cytokine signalling in colon cancer metastasis
Patients with metastatic colon cancer have a poor prognosis and treatment options are very limited.
We investigate cytokine signaling and corresponding activation of TYK2 in colon cancer liver metastasis. The role of TYK2 in colon cancer is not well defined, most likely due to different roles in cancer cells and immune cells. In addition, TYK2 inhibitors are currently being evaluated in clinical trials for use in patients with inflammatory bowel disease. It is therefore important to define possible implications of inhibitor treatment for the formation of primary colon tumors and colon cancer metastasis.