Determining Preclinical Biomarkers of Cancer in Inflammatory Bowel Disease
Job No:
G22
Location:
Darlinghurst, Sydney
Supervisor: A/Prof Kylie James
Link: Dr Kylie James | Garvan Institute of Medical Research
Determining Preclinical Biomarkers of Cancer in Inflammatory Bowel Disease
Individuals with inflammatory bowel disease (IBD) comorbid with primary sclerosing cholangitis, characterised by blockage of the bile ducts, (PSC-IBD) have a 10-fold increased incidence of colorectal cancer (CRC) compared to the general public. Furthermore, PSC-IBD has a higher prevalence of CRC than other IBD phenotypes; for example, PSC-IBD triples the risk of CRC compared with ulcerative colitis (UC) alone. Although PSC-IBD most closely resembles UC, it is clinically distinct with milder severity, a more common manifestation of pancolitis and a unique response to treatments. Additionally, a recent study has shown differences in the intestinal immune responses and faecal microbiota of these patient groups. Together, this research and the clinical presentations point towards unique underlying molecular mechanisms underpinning PSC-IBD and UC and their distinct malignancy risks.
The objective of this PhD project is to leverage state-of-the-art single-cell and molecular profiling technologies to study cellular and microbial drivers of CRC in patients with UC and PSC-IBD. For the first time, this project will determine cellular and microbial signatures that contribute to distinct cancer risks between patient cohorts, and represent early predictive markers of malignancy and routes for treatment.