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Targeting a novel adaptive neovascular response of the tumour microenvironment to treat advanced prostate cancer

Prostate cancer (PCa) is a significant healthcare burden in Australia. Androgen signalling inhibition using androgen receptor (AR) antagonists is the principal systemic therapy for advanced PCa. Androgen receptors (AR) are an attractive therapeutic target due to their elevated expression in tumour epithelial cells and the retention of androgen signalling throughout the disease continuum.However, patients eventually develop resistance to treatment, and PCa cells metastasise to distant bone and visceral organs, representing an incurable stage of the disease. Understanding mechanisms that contribute …

Study level
PhD, Master of Philosophy, Honours
Faculty
Faculty of Health
School
School of Biomedical Sciences

Using a natural β-carboline dimer compound to target metabolic vulnerabilities linked to glycolysis in prostate cancer

Prostate cancer is an androgen dependent cancer and treatments are aimed at preventing activation of the androgen receptor. Part of the development of resistance to therapies involves prostate cancers reprogramming their metabolism to overcome metabolic stress induced by these therapies and support growth and survival. This reprogramming involves increases in the rate of glycolysis and intermediate pathways branching from glycolysis. Previously in our laboratory, the natural compound, beta-carboline dimer, BD, was identified to have potent effects on cell viability, cell …

Study level
Master of Philosophy, Honours
Faculty
Faculty of Health
School
School of Biomedical Sciences

PSA splice variant in prostate cancer diagnosis and pathogenesis

Current clinical prostate cancer screening is heavily reliant on measuring serum prostate specific antigen (PSA) levels. However, two-thirds of these men will not have cancer on biopsy and conversely, other prostate diseases. As a result, for ~75% of patients the large number of indolent tumours diagnosed has led to significant overtreatment creating an urgent need for appropriate prognostic assays that can distinguish indolent, slow growing tumours from the more aggressive and lethal phenotypes. PSA/KLK3 is a member of the tissue-kallikrein …

Study level
PhD, Master of Philosophy, Honours
Faculty
Faculty of Health
School
School of Biomedical Sciences

Proteogenomics of prostate cancer: discovering, characterising and targeting micro peptides encoded by non-coding part of the genome

Next generation RNA sequencing (RNA-Seq) has allowed the identification of entire transcriptomes and has led to the unexpected realisation that a much higher than anticipated portion of the genome is transcribed (up to 85%). A large proportion of these transcripts lack a ‘long’ open reading frame (ORF) and have therefore been considered as long noncoding RNAs (lncRNAs). LncRNAs play dynamic roles in transcriptional and translational regulation.Interestingly, in recent ground-breaking studies lncRNAs were discovered to contain short open reading frame sequences …

Study level
PhD, Master of Philosophy, Honours, Vacation research experience scheme
Faculty
Faculty of Health
School
School of Biomedical Sciences

Biological and clinical impact of the association of germline variations in KLK3 (PSA) gene in prostate cancer

Prostate cancer is the most frequently occurring cancer (after skin cancers) in Australian males, and the second most common cause of cancer death. While the 5-year survival rate for localised disease approaches 100%, extra-prostatic invasion results in a poorer prognosis. Kallikreins are serine proteases, which are part of an enzymatic cascade pathway activated in prostate cancer (Lawrence et al 2010). The most well-known member is prostate specific antigen (PSA) or the KLK3 protein, encoded by the Kallikrein 3 (KLK3) gene, …

Study level
PhD, Master of Philosophy, Honours
Faculty
Faculty of Health
School
School of Biomedical Sciences

Identification and characterisation of IRX4 isoforms as novel targets in prostate cancer

Prostate cancer (PCa) is the second leading cause of cancer-related death in Australian men. There is no cure for advanced prostate cancer patients who develop resistance to currently available treatments. Alternative splicing (AS) is tightly regulated to maintain genomic stability in humans (Liyanage et al 2019). Aberrant RNA splicing of cancer-causing genes has been reported as a major cause of treatment escape in prostate cancer patients. Iroquois-class homeodomain protein 4 (IRX4) is a TALE homeobox transcription factor which has been …

Study level
PhD, Master of Philosophy, Honours
Faculty
Faculty of Health
School
School of Biomedical Sciences

Engineering the prostate tumour microenvironment in organ-on-a-chip systems

Prostate cancer remains one of the leading causes of global death. The tumour microenvironment (TME) including blood vessels, immune cells, fibroblasts, and the extracellular matrix (ECM) possesses disease-specific biophysical and biological factors that are difficult to recapitulate using conventional in vitro cell culture models.The absence of these factors, however, causes cells to display abnormal morphologies, polarisation, proliferation, and drug responses, thereby limiting the ability to translate research findings from traditional cell culture into clinical practice.Recent advances in organ-on-a-chip technology enable …

Study level
Honours
Faculty
Faculty of Health
School
School of Biomedical Sciences

Restoring adiponectin signalling to prevent prostate cancer progression

Advanced prostate cancer (PCa) is a leading cause of cancer-associated death in Australian men. Anti-androgens, which exploit the tumour’s reliance on androgens for its growth and spread, offer temporary remission in advanced PCa patients, but due to treatment resistance, fail to be curative. A further complication of anti-androgens is that they trigger a deleterious suite of metabolic side-effects resembling obesity/Metabolic syndrome. These symptoms not only impact patient health but promote the tumour to be more aggressive and resist treatment. Vital …

Study level
PhD, Master of Philosophy, Honours
Faculty
Faculty of Health
School
School of Biomedical Sciences

Targeting leptin's signalling axis to prevent treatment resistance in prostate cancer

Advanced prostate cancer (PCa) is a leading cause of cancer-associated death in Australian men. Anti-androgens, which exploit the tumour’s reliance on androgens for its growth & spread, offer temporary remission in advanced PCa patients, but due to treatment resistance, fail to be curative. A further complication of anti-androgens is that they trigger a deleterious suite of metabolic side-effects resembling obesity/Metabolic syndrome. These symptoms not only impact patient health but promote tumours to be more aggressive & resist treatment. Vital new …

Study level
PhD, Master of Philosophy, Honours
Faculty
Faculty of Health
School
School of Biomedical Sciences

Prostate cancer transcriptomics (Honours and Master of Philosophy)

At the Australian Prostate Cancer Research Centre QLD, we are interested in the cellular adaptive response processes leading to therapy resistance in advanced prostate cancer.A focus area of our research is studying the transcriptome changes in prostate cancer cell lines, xenograft models and patient samples using RNA sequencing technologies.By integrating our large in-house repository of RNAseq data sets with publicly available studies, this project will further explore the cellular heterogeneity of prostate tumours and the plasticity of cancer cells in …

Study level
Master of Philosophy, Honours
Faculty
Faculty of Health
School
School of Biomedical Sciences

Prostate cancer transcriptomics (Vacation Research Experience Scheme)

At the Australian Prostate Cancer Reseach Centre QLD, we are interested in the cellular adaptive response processes leading to therapy resistance in advanced prostate cancer. A focus area of our research is studying the transcriptome changes in prostate cancer cells and xenograft models using short read RNA sequencing.NextGen sequencing ia a fast progressing field and multiple approaches for sample preparation, processing and data analysis are being used, each with unique advantages and disadvantages. The proposed project at our centre encompases …

Study level
Vacation research experience scheme
Faculty
Faculty of Health
School
School of Biomedical Sciences

A novel molecular targeted therapy for anaplastic prostate cancer

In advanced PCa, where the cancer has spread into the bone and other organs, the emergence of treatment resistance remains inevitable. For decades the primary form of treatment in advanced PCa has been to target the production and actions of male sex hormones, androgens, the primary developmental and survival factor of prostate tissue. While these therapies result in tumour regression and cancer control, this is temporary and treatment resistance occurs, referred to as castrate resistant prostate cancer (CRPC). In the …

Study level
Master of Philosophy, Honours
Faculty
Faculty of Health
School
School of Biomedical Sciences

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