Successful Projects Commencing in 2015
Project One
Project Title: Alteration of the Transcriptome During Acute Carotid Atherosclerotic Plaque Rupture
Chief Investigators: A/Prof Hernan Bazan (Ochsner Clinical School) and Prof Matthew Brown (UQ)
Synopsis: Identifying the mechanisms driving atherosclerotic plaque rupture is complicated by the lack of an adequate animal model. We have developed a novel translational approach of comparing carotid plaques, obtained from asymptomatic and acutely symptomatic patients with carotid disease. Our preliminary data suggests a role for circular RNA in the regulation of micro RNA in plaque development. This project will link changes in the non-coding RNA levels to changes in mRNA leading to atherosclerotic plaque rupture, building a basis for future research into novel diagnostic and therapeutic modalities for the prevention of myocardial infarction and stroke.
Project Two
Project Title: The role of tumor necrosis factor−a in biliary stricture formation in vivo
Chief Investigators: Dr Ari J. Cohen (Ochsner Clinical School) and Prof Darrell Crawford (UQ)
Synopsis: Up to 35% of liver transplant patients exhibit biliary complications, and 8−15% of them die (2,3). One type of biliary complication is the formation of biliary strictures, abnormal narrowing of the bile duct. We have proposed aims to study whether inflammation is one of the causes of biliary stricture formation in an animal model. We expect to find that an immune protein known as tumor necrosis factor−a contributes to stricture formation. The significance of the study is that by determining the cause of stricture formation, we may be able to prevent its occurrence and decrease the post−surgery mortality rate.
Project Three
Project Title: New blood tests for Barrett's oesophagus and oesophageal cancer
Chief Investigators: Dr Michelle Hill (UQ), A/Prof Virendra Joshi (Ochsner Clinical School), A/Prof Andrew Barbour (UQ)
Synopsis: This collaboration capitalises on the expertise and resources of UQ and OCS to translate the blood biomarkers for oesophageal cancer discovered at UQDI. This project aims to (1) validate these biomarkers using an independent OCS cohort of 100 samples, (2) develop clinical laboratory assays to measure the first 2 validated biomarkers, which could be later utilised at OCS and UQSOM in clinical studies, and (3) develop a tissue microarray capturing samples during disease progression, then investigate the tissue expression of selected validated biomarkers. All biological samples are already banked and available at OCS. This project will generate novel resources and assays, and increase the competitiveness for external (NHMRC) funding.
Project Four
Project Title: Understanding the role of lymph node stromal microenvironment in renal cell carcinoma progression
Chief Investigators: Dr Li Li (Ochsner Clinical School/UQ), Dr M’Liss Hudson (Ochsner Clinical School/UQ), Dr Christudas Morais (UQ) and A/Prof Glemda Gobe (UQ)
Synopsis: Metastatic renal cell carcinomas (RCCs) are incurable and fatal. Our hypothesis is that interactions between RCC and lymph node (LN) stromal cells enhance tumorigenicity, growth, metastasis, and chemotherapeutic drug resistance. Our studies will identify molecular signals that play key roles in these events which will lead to novel targeted therapies aimed at blocking RCC−CSC/LN stromal interactions and prevent/treat metastatic RCC. Ultimately, we will test RCC/LN stromal cell interaction blocking agents on individual patient−derived RCC specimens in our unique orthotopic RCC xenograft murine models. The outcome will lead to realistic individualized treatment plans for RCC patients.