Cancer detection and therapeutics
Cancer is a very significant burden for global health, and is one of the leading causes of morbidity and mortality worldwide. In 2012 the WHO reported that there were 14 million new cases of cancer and 8.2 million people died of this disease. Over the next two decades the number of cancer cases is expected to rise by 70% with the most common cancers being lung, prostate, colorectal, stomach and liver in men; and breast, colorectal, lung, cervix, and stomach in women.
Our research has been focused on the two main avenues to improve cancer patient outcomes: early detection and novel therapeutics. We are developing specific diagnostics and prognostics for prostate cancer and this research is being translated through an Australian company Envision Sciences Pty Ltd. Research on molecular imaging is being developed with a second company Rezolve Scientific and imaging agents being investigated in this project are very innovative as they can potentially be used to detect cancer and can also be used to kill the cancer. Altered lipid biology and metabolism is a hallmark of cancer biology and these compounds could be used to develop a much needed generic cancer therapeutic, suitable for all patients who are afflicted by a cancer. For more information contact Professor Doug Brooks or Dr Sally Plush.
Neuropathology in lysosomal storage disorders
The endosome trafficking and exocytosis pathways are fundamental cellular processes for the loading and release of hormones, neurotransmitters and pulmonary surfactant from secretory vesicles. The biogenesis of secretory vesicles involves the formation of immature vesicles at the trans-Golgi, vesicle maturation and transport along microtubule networks and the fusion of these vesicles with the plasma membrane for partial or total release of the secretory vesicle content. This vesicle maturation process involves the exchange of lipids and protein machinery to form mature fusion competent vesicles, and this controls the functionality of the secretory pathway.
Neuropathology is the major clinical problem in MPS IIIA patients, but the exact nature of the event(s) initiating this functional impairment of neurons is unknown. A reduction in neurotransmitter release may be the underlying cause for the development of neuropathology in MPS IIIA, since reduced neuronal communication underlies these cognitive deficiencies. We propose that the biogenesis and or trafficking of secretory vesicles in neurons is disrupted by aberrant heparan sulphate and lipid storage in these cells, impacting on neurotransmitter release that causes the onset of pathogenesis in MPS IIIA patients. For more information, contact Dr Emma Parkinson-Lawrence.
Lung pathology in lysosomal storage disorders
Lysosomal storage diseases (LSD) are a group of more than 70 devastating genetic diseases. They occur because of a defective enzyme that leads to accumulation of waste products within lysosomes which are responsible for cellular waste disposal. This accumulated waste disrupts the function of cells leading to a wide variety of symptoms across different diseases and different individuals, including significant respiratory pathology. How exactly the increased storage leads to different disease manifestations is currently not understood. Specifically we aim to identify the causes and mechanisms of respiratory dysfunction and the role of the pulmonary surfactant system in LSD. We hypothesise that the accumulation of storage material in endosome-lysosome organelles disrupts the intracellular architecture and function of alveolar epithelial cells. This impacts the formation of lamellar bodies responsible for producing pulmonary surfactant which is critical for breathing and fighting respiratory infections. For more information, contact Dr Emma Parkinson-Lawrence or Professor Sandra Orgeig.