Detail

Keywords

Inflammatory Bowel Diseases; Lynch Syndrome II

Research group(s)

• Molecular Cancer Chemoprevention
  Research Area: Our research is focused on the understanding, prevention and treatment of inflammatory bowel disease and colorectal cancer.
  Members:
  Christoph Gasche

Research interests

My laboratory work is translational with the focus on understanding the pathogenesis of inflammatory bowel diseases (IBD), colitis-associated cancer and pharmacological prevention of colorectal cancer specifically in IBD and Lynch Syndrome. We spent ten years on studying the molecular effects of mesalazine (5-aminosylicylic acid), an old drug with multiple effects. We identified PAK-1 as a target of 5-ASA and are now interested in the role of PAKs in intestinal homeostasis. Another project relates to intestinal dysbiosis in IBD as PAK1 is also a target of the bacterial effector ESPG. Recently we got invovled with studying microbiota in intestinal biofilms in patients with irritable bowel syndrome.

Another topic (related to IBD) is iron deficiency (ID) and thomboembolism. The lab has demonstrated that ID drives thrombopoiesis (secondary thrombocytosis) and platelet aggregation. Mechanistically this involves HIFs and VEGFs. Now we are looking into animal models of venous and arterial thrombosis to study the role of ID in such. We are also interested in iron as trigger of inflammation and cancer and have identified Fe-EDTA (as used for food supplementation) toxic compound.

Techniques, methods & infrastructure

Molecular biology, cell culture, intestinal mouse organoids, various mouse models (PAK1, IL-10, MSH2, APCmin, AOM-DSS), rat models of iron deficinecy

Microbiota 16S sequencing, FISH

Access to clinical samples (DNA, RNA, biopsies, surgical specimen) from IBD and CRC

Grants

• PAKs in IBD and associated intestinal cancer (2019)
  Source of Funding: FWF (Austrian Science Fund), Stand-Alone Projects
  Principal Investigator
• Targeting mucosal biofilms in patients with gastrointestinal disorders (2019)
  Source of Funding: WWTF (Vienna Science and Technology Fund), Linking Research and Patients' Needs
  Principal Investigator
• Mucosal biofilms in ulcerative colitis (2016)
  Source of Funding: FWF (Austrian Science Fund), Programme Clinical Research (KLIF)
  Principal Investigator
• Megakaryopoiesis, Thrombosis and Iron Deficiency - MegIron2 (2015)
  Source of Funding: FWF (Austrian Science Fund), Stand-Alone Projects
  Principal Investigator
• "MesaCapp" - Mesalamine for Colorectal Cancer Prevention Program in Lynch syndrome (2013)
  Source of Funding: FWF (Austrian Science Fund), ERA-Net on Translational Cancer Research
  Coordinator of the collaborative project
• Ulcerative colitis and microsatellite instability (2011)
  Source of Funding: FWF (Austrian Science Fund), Stand-Alone Projects
  Principal Investigator

Selected publications

1. Dammann, K. et al., 2015. PAK1 Promotes Intestinal Tumor Initiation. Cancer Prevention Research, 8(11), pp.1093-1101. Available at: http://dx.doi.org/10.1158/1940-6207.CAPR-15-0205-T.
2. Jimenez, K. et al., 2020. Iron deficiency induced thrombocytosis increases thrombotic tendency in rats. Haematologica, p.haematol.2019.245092. Available at: http://dx.doi.org/10.3324/haematol.2019.245092.
3. Kortüm, B. et al., 2014. Mesalazine and thymoquinone attenuate intestinal tumour development in Msh2loxP/loxPVillin-Cre mice. Gut, 64(12), pp.1905–1912. Available at: http://dx.doi.org/10.1136/gutjnl-2014-307663.
4. Frick, A. et al., 2018. Overt Increase of Oxidative Stress and DNA Damage in Murine and Human Colitis and Colitis-Associated Neoplasia. Molecular Cancer Research, 16(4), pp.634–642. Available at: http://dx.doi.org/10.1158/1541-7786.MCR-17-0451.
5. Lang, M. et al., 2017. HuR Small-Molecule Inhibitor Elicits Differential Effects in Adenomatosis Polyposis and Colorectal Carcinogenesis. Cancer Research, 77(9), pp.2424–2438. Available at: http://dx.doi.org/10.1158/0008-5472.CAN-15-1726.