The research of the Toivola lab is focused on the roles, regulation and diagnostic potential of keratin intermediate filaments in gastrointestinal epithelia of the intestine and the endocrine pancreas, in health and during autoimmune diseases in these organs.
Keratins are dynamic cytoskeletal proteins that provide mechanical stability to cells and are important in protection from cellular stress and in signal transduction regulation. Keratin mutations predispose humans to diseases, including liver disease. Whether inflammatory bowel diseases (IBD) or type I diabetes are linked to keratin mutations in humans is currently unknown. Loss of the main simple epithelial keratin, keratin 8 (K8), in mouse models leads to an early IBD phenotype and strong susceptibility to colorectal cancer, and in the endocrine pancreas to defect glucose sensing.
Our aims are to understand how keratins help protect simple type epithelia on a molecular level in healthy tissues and in disease context, including inflammatory bowel diseases, colorectal cancer and type I diabetes. Using tissue specific transgenic and experimental mouse models of colitis, colorectal cancer, diabetes, as well as cell and organoid cultures we study the mechanics and roles of keratins in epithelial cells. We also discover novel biomarkers in the colon of IBD patients and aim to develop non-invasive diagnostic biochemical and imaging methods for these diseases.
