Project Title: Understanding the role of lymph node stromal microenvironment in renal cell carcinoma progression: Phase 2 ‐identifying personalized therapeutic strategies
Chief Investigators: Dr Li Li (Ochsner Clinical School/UQ), Dr Stephen Bardot (Ochsner Clinical School/UQ), Dr Christudas Morais (UQ) and A/Prof Glemda Gobe (UQ)
Synopsis: Renal cell carcinoma (RCC) is a complex disease with widely varying prognosis. Metastatic RCC is incurable and fatal. Our hypothesis is that RCC and lymph node (LN) stromal cell interactions enhance tumourigenicity, metastasis, and drug resistance. We have established patient‐derived orthotopic xenograft (PDOX) models in which RCC metastasize to distant organs under LN stromal microenvironment influence. We aim to identify the molecular signals involved and test conventional, targeted therapies including RCC/LN stromal interaction blocking agents, and combination therapies, on individual patientderived RCC specimens in unique PDOX models. The study outcome will lead to realistic individualized treatment plans for RCC patients.
Project Title: Alteration of the Transcriptome During Acute Carotid Atherosclerotic Plaque Rupture , Year 2 Study
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. Ourpreliminary 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 Title: The role of the cancer stem cells in colorectal cancer metastasis
Chief Investigators: Prof David Margolin (Ochsner Clinical School/UQ), Dr Li Li (Ochsner Clinical School/UQ) and A/Prof John Hooper (UQ)
Synopsis: Metastatic spread causes 90% of colorectal cancer (CRC) deaths. Cancer stem cells (CSC) are thought to play a key role not only in metastasis but also in resistance to chemo‐ and radio‐therapy. We have previously shown that interactions between CRC‐CSC and the lymph node (LN) stromal microenvironment are important in CRC metastasis. Our hypothesis is that CRC‐CSC that co‐express the receptors CD133, CXCR4 and CD318 are responsible for CRC extra‐nodal metastasis and that these proteins mediate pro‐metastatic interactions with stromal cells. Our objective is to investigate these interactions using our novel molecular tools and mouse models generated from CRC patients.
Project Title: Placenta-derived exosomes, a possible biomarker for early detection of complication of pregnancies
Chief Investigators: Dr Carlos Salomon Gallo (UQ) and Dr Sherri Longo (Ochsner Clinical School)
Synopsis: Of the 130 million babies born each year, 8 million die before their first birthday. A contributing factor in many of these deaths is poor outcome from complications such as preeclampsia (PE), intrauterine growth restriction (IUGR), and preterm birth (PB), which affect around 15% of all pregnancies. This project will deliver novel insights into the role of placental exosomes (i.e. nanovesicles that transport molecular signals between cells) in normal pregnancies and in those complicated by placental dysfunctional. We will identify targets for therapeutic interventions and placental exosomal biomarkers of at risk pregnancies, thus facilitating the development of early screening.