Current approved research projects

There are close to 1700 lives saved by solid organ transplant (SOT) in Australia each year. Infection and immunological complications represent the major determinants of morbidity and mortality and also drive transplant-associated costs so there is an economic as well as clinical imperative for investigating novel approaches to predicting and treating these complications despite existing strategies. Specific bacterial microbiome signatures have been associated with risk of infections and immunological complications after transplant in previous studies. Risk for acute cellular rejection and blood stream infection after liver transplant have both been correlated with microbiome diversity in small single centre cohorts. But understanding of the mechanisms underlying interactions between bacterial and non-bacterial microbial complements, infectious risk and graft survival is currently limited.  Definition of these components in well-defined transplant cohorts is essential to capitalise on any opportunity they may present for translation into targets of novel diagnostics and therapeutics. 

T  cells  protect  us  against  infection  and  cancer,  yet  dysfunctional  T  cells  cause autoimmune disease. Our knowledge of human T cells largely comes from research using blood and information on how T cells work in solid organs like the gut and lung is  scarce.  This  project  aims  to  decipher  how  T  cells  function  in  various  organs  in health and disease. The expected outcomes are to gain new knowledge so that we can design new treatments for infection, cancer, and autoimmune disease. 

The immune system is a potent weapon for protection against pathogens, including viruses like influenza. T-cells have a central role as their receptors monitor the body for threats. The thymus educates T-cell receptors to discriminate between healthy and infected cells. Receptor diversity and T-cell strength change throughout human life. This project aims to unravel how T-cells gain and lose optimal receptors and strength by understanding how the thymus educates receptors throughout human life. The project is essential for understanding how optimal T-cell immunity is formed, critical if we wish to improve healthy aging and protect against viral infections like influenza. 

Heart disease is the leading cause of death in the world. While the causes of cardiovascular disease are typically multi-factorial (diet, genetics, age etc), there is a growing realization that cells of the immune system are active participants in maintaining cardiac homeostasis (i.e. a healthy heart) and conversely, damaging the heart during periods of disease. In this project we will explore this role, characterizing the immune cells that reside within the human heart and determine how these populations act. 

For our bodies to fight off infections or cancer, complex interactions need to take place between white blood cells. Some cells capture and present foreign matter to other cells, in a process called 'antigen presentation'. This occurs in all the tissues of our body, however there is much unknown in humans due to the difficulty in obtaining tissue samples. Using human organ donor samples provided by the ADTB, we will measure these cells’ activity in blood and multiple lymphoid, visceral and barrier tissues. The new insights gained in this area will lead to new treatments for diverse diseases. 

Healthy immune responses help fight infection and cancer, while destructive immune responses lead to autoimmune disease. Immune responses occur in diverse tissue sites like the lung, liver and gut, however, our understanding of human immunology is largely derived from the sampling of blood. Using human organ donor samples provided by the Australian Donation and Transplantation Biobank (ADTB), we will characterise immune responses with a focus on MR1-reactive T cells, a specialised set of small metabolite reactive T cells, in blood and multiple lymphoid, visceral and barrier tissues.  A greater understanding in this area will lead to new treatments for infections, cancer and autoimmune diseases. 

Spectroscopy is a new, powerful analytical technique that has numerous applications in the field of medicine, including in the diagnosis and treatment of heart disease. Spectroscopy can provide valuable insights into the composition and structure of the heart tissue, including using spectroscopy to detect changes in the chemical composition of heart tissue, such as alterations in the levels of lipids, proteins, and carbohydrates. This can help further explain and diagnose conditions such as cardiomyopathy, by using spectroscopy to capture a chemical snapshot to characterize the structural changes present in both the healthy versus the diseased heart. 

Internal organ tissues become stiffer with age. This stiffening is accelerated by fibrotic diseases which result in scarring of internal organs such as lung, liver, and heart. Fibrotic diseases are progressive, lead to organ failure and currently there is no cure. Our research program is revealing a new understanding of the scar process, leading to identification of multiple new drug targets with potential to treat fibrotic diseases.

The immune system can be activated by a range of foreign stimuli such as viruses, prescribed drugs, donor tissue grafts or even self-antigens. These stimuli are presented to the immune system in the form of small protein fragments, called peptides, by specialised molecules on the surface of cells known as human leukocyte antigens (HLA). A specific set of immune cells, called T cells, recognise different peptide/HLA complexes that can trigger either protective (e.g. anti-viral, anti-cancer) or undesirable (e.g. anti-graft, autoimmune, allergy) immune responses. This project seeks to identify peptides from a range of human tissues to determine their involvement in different human diseases.   

Many aspects of bladder function (voiding, continence) involve communication between the bladder and the nervous system. In this project we aim to visualize these “nerve-organ connections” in order to construct a map of this nerve patterning. This will be achieved using state-of-the-art microscopy. It has not previously been possible to obtain this fundamental data as complete specimens of healthy bladder tissues have rarely been available. Our results will benefit urological research, so that we can better understand what is required for healthy bladder function and interpret the changes occurring in urological disease states (including incontinence, pelvic pain and bladder cancer).   

Nerve fibres innervate nearly all tissues in the body.  Our interests are in understanding the nerve fibres that innervate the air passages and lungs, because these have altered function in lung disease states, contributing significantly to the symptoms experienced by patients.  We aim to map and characterize nerve fibres in the airways and lungs to better understand how the nervous system may contribute to the symptoms of disease.  

Chronic respiratory diseases pose a major public health problem, accounting for 7% of death worldwide (WHO, 2019). We aim to understand the effect of environmental insults on the development of lung disease. Through the analyzing of human lung cells after exposure to cigarette smoke or infections, we aim to better understand the pathology of lung diseases, including COVID19, COPD and lung cancer. The outcomes of this project will be to identify novel therapeutic approaches to prevent or reduce the risk of developing chronic respiratory diseases. 

The lymphoid tissues (including the spleen and lymph nodes) are critical for the body to mount immune responses to fight off diseases. These tissues are constructed by stromal cells that are presumed to serve multiple important functions. We aim to determine the role of the lymphoid tissue stromal cells on the functions of these tissues. This is important to identify new targets for the development of novel therapies that can halt the spread of diseases including cancer. 

As disease burdens rise and health systems are overwhelmed globally, the urge to find new treatment strategies becomes imperative. Human gamma-delta T cells are essential components of the immune system, highly represented in solid tissues and at mucosal barriers. However, they remain poorly understood. These cells are thought to play a critical role in the immune system’s ability to monitor tissues and organs for disease and damage. Our research will provide a comprehensive understanding of gamma-delta T cells’ structure and function, endeavouring to translate this research clinically. The aim is to limit the impact of diseases including infection and cancer. 

The Translational Oncology Discovery Group is particularly interested in engineering novel antibody-based cancer therapies that can directly target certain tumour cells and, simultaneously, also targets key immune cell proteins, therefore combining two cancer therapy approches in one drug. Importantly, our approach to cancer drug development is informed by the “reverse translational research” paradigm. This means that we utilise cutting-edge translational experiments using patient-derived materials from on-going cancer clinical trials to help understand mechanisms and design the next generation of cancer therapies. Currently, we are engaged in clinical trial activities that include experimental treatments for patients with non-small cell lung cancer, head and neck squamous cell carcinoma and melanoma.  

​Calcific Aortic Valve Disease (CAVD) is a common condition causing thickening and narrowing of the heart’s aortic valve. While CAVD can be diagnosed easily and early, there are currently no drugs or medications able to slow the progression of heart valve disease, and the only option is valve replacement. We know that immune cells and inflammation are present in diseased heart valves, which may be treatable in early stages. We are analyzing the cells and structure of heart valves from participants with and without CAVD to identify targets for drug treatments to slow or stop progression of aortic valve disease.