Colorectal Medicine and Genetics
Serrated Polyposis Syndrome - also offered as MBiomedSc - also offered as MBiomedSc
Supervisors: Professor Finlay Macrae
Project Site: The Royal Melbourne Hospital
Contact: E: finlay.macrae@mh.org.au
Project description: Serrated polyposis syndrome is the last polyposis syndrome without a known genetic predisposition identified. Working with Dr Dan Buchanan in the Dept of Pathology, this project will be the clinical arm of phenotype data collection from the records of the Familial Cancer Clinic which will form the basis for the selection of cases for next gen whole genome sequencing in Dan’s lab in the Dept of Pathology
Prospective studies on penetrance for cancer in Lynch Syndrome - also offered as MBiomedSc
Supervisors: Professor Finlay Macrae
Project Site: The Royal Melbourne Hospital
Contact: E: finlay.macrae@mh.org.au
Project description: Well- designed studies on prospectively collected data for studying penetrance, survival and treatment effects of cancers occurring in Lynch Syndrome are scarce. This project will collaborate with European investigators on a common design template to provide important data to guide clinical practice. Two consortia are already formed with whom the candidate will collaborate: the International Mismatch Repair Consortium (leads Robert Hale, Stanford, Mark Jenkins and Finlay Macrae (Melbourne) and Gabriela Moeslein (Dusseldorf, Germany); and the Majorca Group (lead Pal Moller, Norway
CAPP3: a randomized controlled trial of aspirin dosage in Lynch Syndrome - also offered as MBiomedSc
Supervisors: Professor Finlay Macrae
Project Site: The Royal Melbourne Hospital
Contact: E: finlay.macrae@mh.org.au
Project description: CAPP2 proved aspirin reduces the incidence of LS associated cancers by over 50%. CAPP3 is a dose finding RCT testing 100mg vs 300mg vs 600mg. This si an international study lead from Newcastle UK, with Australian leadership from RMH. Students will learn about multi centre, multi national RCTs, be immersed in aspirin science and cancer genetics, and participate in the clinical aspects of management of Lynch Syndrome.
Locus Specific Databases in Hamartomatous polyposis syndromes
Supervisors: Professor Finlay Macrae
Project Site: Department of Colorectal Medicine & Genetics, Royal Melbourne Hospital
Contact: Professor Finlay Macrae E: Finlay.macrae@mh.org.au
Project description: Hamartomatous polyposis syndromes include : Peutz Jeghers Syndrome (gene locus STK11), Juvenile Polyposis (gene loci SMAD4 & BMPR1A, Cowden’s Syndrome (gene locus PTEN). Diagnostic laboratories around the world identify in the gene loci, sometimes clearly pathogenic, other times uncertain. International centralisation of gene variant information with clinical and familial information is one of the best ways to progress the interpretation of variants of uncertain significance. The Human Variome Project, at the University of Melbourne, aims to document variation in all genes across all countries in the world. The Hamartomatous Polyposis Syndrome project will relate to the HVP. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) hosts LSDB’s for genes responsible for inherited gastrointestinal cancers. The InSiGHT mismatch repair gene database is curated at the HVP and Department of Colorectal Medicine and Genetics at The Royal Melbourne Hospital. The Hamartomatous Polyposis LSDB Project will develop similar database, ascertaining variant and clinical data across the published literature, contacting the InSiGHT membership for unpublished information and assembling the data on a LOVD platform. The project will involve extensive international collaboration, understanding genetic variation and variants of uncertain significance, bioinformatics and clinical management of these syndromes.
The Structure and Functions of an Inflammatory Bowel Disease Service
Supervisors: Professor Finlay Macrae
Project Site: Department of Colorectal Medicine & Genetics, Royal Melbourne Hospital
Contact: Professor Finlay Macrae E: Finlay.macrae@mh.org.au
Project description: This project will assist the IBD Service and the IBD Nurse Consultant to refine the structure required for the Inflammatory Bowel Disease Service through:
Development of clinical guidelines to manage well defined IBD Clinical management issues (eg. acute colitis)/ Integration with the new Pharmaco-genetics Service at The Royal Melbourne Hospital (ie. TPMT genotyping). Thiopurine metabolite testing. Transition arrangements of IBD patients from paediatric to adult care. Bone density monitoring and intervention. “Off label” use of anti TNF therapies eg. in ulcerative colitis. The Royal Melbourne Hospital IBD Database. The functions of one of several of these will be tested through “before and after” assessment, where appropriate and audits and /or surveys.
The project will provide an outstanding opportunity for clinical engagement in a busy IBD Service, collaboration with other Australian IBD services, understanding of the evolving role of IBD Nurse Practitioners in IBD care, endoscopy in IBD, and interaction of the clinical IBD service with a range of clinical research projects (microbiota pharma trials)
PillCam Colon and IBD - also offered as MBiomedSc
Supervisors: Professor Finlay Macrae
Project Site: The Royal Melbourne Hospital
Contact: E: finlay.macrae@mh.org.au
Project description: THE Royal Melbourne Hospital has the only substantial experience of PillCam colon use in Australia. This “camera in a pill” technology is now available for imaging the whole gastrointestinal tract. Research students have provided the most extensive experience with the technology in assessing mucosal healing in Crohn’s Disease. Further studies are available refining bowel preparation for the procedure, conducting intereobserver stusies, and comparing any changes in clinical management as a result of the information provided by the capsule.
This project is attractive to Scholarly Selective students; Honours students need to express interest early!
C-reactive protein (CRP) and Crohn's disease - CRP as a potential phenotypic marker for disease
Supervisors: Dr Suresh Sivanesan, Prof. Finlay Macrae
Project site: Royal Melbourne Hospital, Parkville
Contact: Dr Suresh Sivanesan T: 03- 8417 9900 or 03- 9342 7584 E: suresh.sivanesan@mh.org.au
Project description: Crohn’s disease is a chronic inflammatory condition which can affect any part of the gastro-intestinal tract to cause significant symptoms and morbidity. The condition can affect and segment of the gastrointestinal tract including the perianal region. It can develop into more complex disease resulting in abscesses, luminal strictures, fistulas and perforation. Clinicians have sought to classify Crohn’s disease in terms of the disease distribution or complications that it has caused. The currently used classifications are helpful but they do not assist in reliably predicting appropriate treatment or outcomes.
CRP is a serum inflammatory protein that is commonly elevated in conditions such as rheumatoid arthritis, infection and Crohn’s disease. It is produced by hepatocytes and is upregulated by cytokines IL-6, IL1β and TNFα. It has been described that not all patients with Crohn’s disease exhibit a rise in CRP. We hypothesize that if there are a subgroup of patients with active Crohn’s disease and a express a normal serum CRP.
We intend to study our cohort of patients with active Crohn’s disease to determine their levels of CRP, disease phenotype and assess their response to treatment. In particular if the hypothesis is true, we would hope to extend this work in the future to include cytokine and genotypic profiling of these patients.
This work could open the door toward a better understanding of Crohn’s disease using widely available tools such as CRP. In future identifying subgroups of patients with Crohn’s disease based on cytokine and genetic profiling will enable a more tailored approach to patient care.