Detecting diseases of the intestinal tract earlier: what do we need to measure?


Detecting diseases of the intestinal tract earlier: what do we need to measure?

Tue, 11/12/2018 - 11:00


Professor Inke Näthke
University of Dundee

Diseases of the intestinal tract are increasing and contribute significantly to health care costs worldwide: Colon cancer is the second most common cause of cancer deaths in the developed world and inflammatory conditions of the intestinal tract affect more than 0·3% of the population in North America, Australia, and many countries in Europe. For both, cancer and inflammatory conditions, early detection, before overt disease has developed, and the ability to detect residual and recurring disease are crucial for successful treatment of patients. Professor Inke Näthke established key functions of the Adenomatous Polyposis Coli (APC) protein, the major tumour suppressor for cancers in the lining of the intestinal tract. She defined roles for APC in tissue functions including cell migration, division, death and stem cell behaviour in situ, providing insight into the role of mutant APC in oncogenesis. She provided the first evidence for the complex relationship between different APC protein interactions during cell signalling with implications for the sensitivity of APC-deficient cells to chemotherapeutics. Her aim is to use cell biological and biochemical insights to develop improved methods for detecting disease. The most commonly used approaches for diagnosing diseases in the intestinal tract, rely on visual inspection, clinical imaging and traditional histopathology. The latter involves physical access to diseased tissue areas and removing biopsies and can only detect disease once sufficiently progressed to be visible. To detect disease of the intestinal tract earlier so that patients can be treated more effectively, will require new modalities that can measure how cells and tissues change during earlier disease states making it important to understand the details of these changes.
Using an APC-mutant mouse model, we found that High Frequency Ultrasound (HFUS) detects changes in tissue structure that precede cancer in the small intestine and are the result of cell biological changes induced by mutations in APC. High resolution optical images of precancerous, histologically normal tissue revealed more irregular structure of the tissue lining the small and large intestine. HFUS reliably detected this change suggesting that can detect precancerous tissue changes in the intestinal tract in patients, which would facilitate earlier treatment to improve clinical outcome. The possibility of incorporating HFUS into capsule endoscopes, which would provide access to the small and large intestine, the sites of inflammatory conditions, prompted explorations to test if HFUS could also detect early stages of inflammation. Preliminary results predict that tissue changes in early inflammation are amenable to detection by HFUS. Together these results raise the exciting possibility that inflammatory diseases and cancer could be detected along the entire intestinal tract much earlier making them much more amenable to successful treatment.


Professor Inke Näthke completed a BSc in Biochemistry at San Jose State University in California. After work on the development of transdermal drug delivery devices she attended the University of California San Francisco where she obtained her PhD in Pharmaceutical Chemistry. Her PhD work provided novel insights into structure-function relationship of clathrin, the key component of the protein machinery responsible for receptor-mediated endocytosis. She then pursued postdoctoral training at Stanford University working on the dynamics of proteins involved in cell adhesion. There she discovered the adenomatous polyposis coli (APC) tumour suppressor protein as an important cytoskeletal regulator. She continued to pursue studies on the role of APC and its interaction with microtubules at Harvard Medical School before joining the faculty at the University of Dundee where she is currently the Professor of Epithelial Biology in the Division of Cell and Developmental Biology. Her research aims to understand the earliest changes in gut tissue that accompany initiation and progression of tumours and inflammation. Using biochemical and cell biological techniques plus high-resolution imaging and isolated proteins, single cells, and whole tissue, her laboratory investigates how cell and tissue dynamics are altered by mutations in APC and cytokines to understand these diseases better and develop improved tools for their early and robust detection.