Conjoint Gastroenterology

The Conjoint Gastroenterology Laboratory studies the molecular genetic alterations which underlie the progression of benign bowel polyps to bowel cancer.  It has a particular interest in serrated polyps which were previously thought to have no malignant potential but are now recognised to be the precursors of approximately 20% of bowel cancers.  This work has led to profound changes in the practice of colonoscopy so that it now better protects against bowel cancer.  The laboratory has now developed an animal model of the serrated pathway and are testing chemoprevention strategies.  The bowel cancers which arise through the serrated pathway often carry an oncogenic BRAF mutation and develop DNA methylation silencing important genes such as mismatch repair genes.  These characteristics are important in predicting prognosis and response to chemotherapy and this is also a focus of our research programme.  Collaboration with gastroenterologists, surgeons, pathologists and oncologists is a key aspect of its research.

CURRENT RESEARCH

  • molecular alterations causing progression of the serrated polyp to colorectal cancer and better identification of high risk polyps
  • utilising a mouse model to understand the association of BRAF mutation with DNA methylation in the serrated neoplastic pathway and as a pre-clinical model of chemoprevention strategies
  • discovering further genetic changes underlying different subtypes of colorectal cancer which may enable improved chemotherapy options
  • understanding clonal heterogeneity in primary and metastatic colorectal cancers

Staff

  • Dr Catherine Bond, Research Officer
  • Diane McKeone, Scientific Technical Officer
  • Dr Jennifer Borowsky, PhD Student
  • Alexandra Kane, PhD Student
  • Lochlan Fennell, PhD Student
  • Emma Sievwright, PhD Student
  • Chang Su, Honours Student
  • Professor Barbara Leggett, Clinical Affiliate
  • Dr John Liu, Clinical Affiliate
  • Dr Mark Bettington, Clinical Affiliate

Internal Collaborators

External Collaborators

  • A/Prof Neal Walker, Envoi Specialist Pathologists
  • Dr Ian Brown, Envoi Specialist Pathologists
  • A/Prof Christophe Rosty, Envoi Specialist Pathologists
  • Dr Matthew Burge, Cancer Care Services, RBWH
  • A/Prof David Wyld, Cancer Care Services, RBWH
  • A/Prof Melissa Eastgate Burge, Cancer Care Services, RBWH
  • A/Prof Daniel Worthley, South Australian Health and Medical Research Institute
  • Dr Susan Woods, South Australian Health and Medical Research Institute
  • Prof John Mariadason, Olivia Newton-John Cancer Research Institute
  • Prof Shuji Ogino, Dana-Faber Cancer Institute, USA
  • Prof Akinobu Taketomi, Hokkaido University, Japan
  • National Health and Medical Research Council
  • Cancer Council Queensland
  • Gastroenterological Society of Australia
  • RBWH Foundation
  • Pathology Queensland

STUDENT PROJECTS

Genetic changes underlying colorectal cancer initiation and progression

In the Conjoint Gastroenterology Laboratory we are interested in characterising the genetic changes underlying the progression of pre-cancerous colonic polyps to colon cancer. We work closely with clinicians specialising in Gastroenterology, Pathology, Oncology and Genetics to increase our understanding of this disease and improve patient management and outcomes. Potential Honours and PhD projects will examine candidate genes for a role in the development of colorectal cancer, selected from bioinformatic analysis of genome-wide data including expression arrays, DNA methylation array profiling and next generation genomic sequencing. Candidate genes will be examined in a clinically and molecularly well-defined series of colorectal polyps and cancers. Functional studies will be conducted in colorectal cancer cell lines and in xenograft models. Projects are also available to examine strategies for pharmacoprevention using our BRAF mutant murine model. Conjoint Gastroenterology

Find Out More

Colorectal cancer – from genetics to chemoprevention

This project will use a well-developed in vivo model to investigate the role of various drugs in the prevention of bowel cancer. Using an inducible BRAF mutant mouse, we have observed the sequential development of intestinal hyperplasia, polyps and ultimately advanced cancer, in a model that closely mimics human serrated neoplasia. This project will investigate […]

Find Out More