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Clinical Sciences Research

Our clinical sciences research stream is investigating the causes and impacts of common diseases, and translating those findings into more effective treatments for patients on a local, national and global scale.

Our flagship programs in clinical sciences research

Clinical sciences researchers at the Ingham Institute are working on one of the world’s largest-ever genomic studies to help eradicate the superbug Golden Staph. This antibiotic resistant disease is the cause of major hospital-acquired infections around the world and is an emerging cause of infections in the community. Our scientists are using whole genome sequencing to identify genes, mutations and unique elements that enable these bacteria to thrive in these environments.

Other researchers also are focused on the complications arising from diabetes, the sixth leading cause of death in Australia. South Western Sydney has one of the highest prevalence rates of diabetes in NSW and complications from this disease can significantly impact people’s quality of life. Our scientists are investigating diabetic foot disease, in-patient management, diabetic cardiomyopathy, diabetes in pregnancy, and diabetic retinopathy.

There is also a pressing need for better treatment for people with arthritis and autoimmune disease. Clinical science researchers from our Arthritis Research team are involved in finding and evaluating biomarkers (disease characteristics) and patient-reported outcomes to transform the clinical assessment of patients who have connective tissue diseases.

The Correlative Microscopy Group was formed in 2013 with the mission to apply correlative microscopy (CLEM) techniques to enhance the study of disease processes in human tissue samples. This emerging technology aims to integrate “form and function” information from multiple microscopy modalities for improved visualisation of disease related changes. This approach covers multiple scales from the organ level to the single molecule.

Our practical aim is to maximise the information obtainable from routine human biopsy and surgical tissue samples and to correlate this information with clinical imaging. The power of CLEM lies in linking clinically diagnosed disease to changes or interactions in single cells. Biomarkers can be labelled and their participation in the disease process tracked. Key proteins forming sites of drug action or drug failure can be identified.

We have recently obtained grants from the Cancer Institute of NSW, NSW Health Pathology, Ingham Institute and UNSW Australia to create a new facility to apply this approach in cancer research.

In June 2016 saw the Correlative Microscopy Facility established with a state-of-the-art electron microscope (FESEM) commissioned. This is the first FESEM in Australia dedicated to cancer biomarker detection in human tissue. Optimised to use the combined strengths of cryogenic cell preservation and nanotechnology, it is one of the most powerful microscopes of its type in the world.

In June 2017 a correlative superresolution laser scanning microscope (SRLSM) will be commissioned to complement the facility’s CLEM workflow.

Our aim is to understand the molecular mechanisms regulating liver inflammation, fibrosis, cirrhosis and cancer as well as using transgenic animals to model human liver disease with a view to developing novel therapeutic agents as well as new tools for diagnostic investigations.

The current focus of the research group is to further understand the role of the glycoprotein CD147 (extracellular matrix metalloproteinase inducer; EMMPRIN) in mediating basic and fundamental aspects of tissue inflammatory responses and carcinogenesis. Our group has made the fundamental discovery that CD147 mediates a process of inflammatory cell aggregation, which determines the extent of liver injury. Based on this novel discovery we found that if CD147 is blocked in vivo a marked reduction in liver injury was seen in mouse models of liver disease, which has the potential to lead to new therapeutic agents.

Clinical research undertaken by his group examines the use of probiotics to change the composition of the gut flora, treatment of muscle cramps, the use biomarker predictors of liver injury and nutritional interventions in end stage liver disease.

The Rheumatology Research Group are focused on improving the lives of people with musculoskeletal and autoimmune diseases.  The group has embedded research into clinical practice at Liverpool Hospital, with a patient centred approach that records patient reported outcome measures at every visit.

The Rheumatology Research Group offer a variety of sub-speciality clinics that focus on specific groups, including those with psoriatic arthritis, systemic lupus erythematosus and systemic sclerosis, allowing a variety of clinical and laboratory projects.  Our collaborations include research into the 3 most common musculoskeletal conditions: osteoarthritis, osteoporosis and back pain.

The group participate in a number of other national and international collaborations including the Asia Pacific Lupus Collaboration, the Australian Lupus Registry and Biobank and the Australian Scleroderma Interest Group.  The group offer a number of supervised research projects for undergraduate and postgraduate research students, and includes a clinical trials unit that participates in numerous multicentre studies.

Strains of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) are a major cause of healthcare-associated (HA) infections around the world and are concomitant with increased health-care costs, morbidity and mortality; the intractability of such infections is largely due to the capacity of strains to develop resistance to most clinically relevant antibiotics. In this regard, molecular analyses have revealed that widespread multi-resistance has been driven by strong selection pressure and the acquisition of pre-existing determinants, thus highlighting the significant role of mobile genetic elements in the adaptive evolution of these hospital pathogens.

The ARMEGs integrated research program focusses on addressing this global healthcare issue through three main areas of research: molecular epidemiology of pathogen transmission, antibiotic development (i.e., of new/novel compounds) and the evolution of antibiotic resistance, and the role of biofilms as pathogen reservoirs and in various pathologies.

The Stroke and Neurology Research Unit is a collaboration of clinicians and researchers within the South Western Sydney Local Health District (SWSLHD) and the Ingham Institute for Applied Medical Research led by A/Prof Dennis Cordato. Our research focus is stroke and neuroscience and we have a number of exciting research opportunities for Independent Learning Projects (ILP), Honours, Masters or Doctor of Philosophy (PhD) students.

The SWSLHD has one of the largest stroke referral centres in NSW including a very active endovascular clot retrieval service. The research group has a special interest in providing excellence in the diagnosis and management of acute stroke patients. Studies underway or completed include: (i) factors associated with delayed presentation and misdiagnosis of cerebellar infarction which was recently published in the journal, Cerebrovascular Diseases, (ii) investigation of the frequency, aetiology and outcome of small cerebellar infarction, (iii) the role of vestibular function testing as a bedside tool in the Emergency Department to differentiate benign causes of acute vestibular syndrome from posterior circulation stroke, (iv) outcome studies of acute ischaemic stroke patients receiving endovascular clot retrieval, (v) factors contributing to the misdiagnosis of stroke in the Emergency Department  and (vi) optimisation of secondary stroke prevention.

The founding member, Associate Professor John Worthington continues his work on PRISM (Programme of Research Informing Stroke Management), a study which assessed long-term survival of patients following transient ischaemic attack. PRISM II, which commenced in 2017, will address unwarranted clinical variation in the management of intracerebral haemorrhage. His other research studies include NHMRC funded DESPATCH, STOP-STROKE and OASIS (a data-linkage study of subarachnoid haemorrhage epidemiology, outcomes and management in Australia), as well as the HIAC (Hydrocephalus in Adults and Children Study) and CARERA Studies (Cerebrovascular AutoRegulation and ReActivity Study).

The Stroke and Neurology Research Unit has a dedicated clinical trials staff and is actively involved in a number of clinical trials. These include a randomised controlled trial of a Chinese herbal therapy for vascular dementia, and the TASTE (Tenecteplase v Alteplase for Stroke Thrombolysis Evaluation) study. TRIDENT, a randomised controlled trial of low dose combination antihypertensive therapy in patients with intracranial haemorrhage, is expected to commence in the second half of 2017 with The George Institute.

Mission Statement

The Stroke and Neurology Research Unit aims to promote collaborative research within SWSLHD and external partners to deliver health excellence for the population of South Western Sydney.

The Immunology team (A/Prof John Quin, Dr Louise Evans and Dr Catherine Toong) are committed to improving the diagnosis and treatment of patients with immune-mediated diseases. The Unit is involved in a randomised controlled trial to investigate the efficacy of new medication in HIV affected patients. Research into the use and improvement of diagnostic tests for autoimmune diseases such as systemic lupus erythematosus (SLE) is continuing. A number of other diagnostic laboratory audits and quality control measures are underway.

The Department of Respiratory Medicine is conducting clinical research in diverse fields including asthma, COPD, bronchiectasis, sleep disorders, tuberculosis and interventional pulmonology. In addition, several of our researchers are engaged in public health and epidemiological research on sleep disorders, tuberculosis, asthma and COPD.  Some of the studies we are currently running include:

  • New treatments for severe asthma
  • Novel ways of reducing flare-ups in people with bronchiectasis
  • Alternative treatments to prevent tuberculosis in people who have been infected with the TB germ
  • Changes in asthma and allergy during adolescence

Cardiovascular diseases, and particular clinical manifestations of coronary heart disease (CHD), are the major contributors to morbidity in the ethnically and culturally diverse population of South Western Sydney, where its prevalence is increased and CHD is the leading cause of death. Advances in pharmacologic and interventional treatments and recent developments in cardiac imaging can facilitate enhancements in patient care.

The Institute’s Cardiology Centre provides a nexus for cardiology research and academic strength. Key strengths include the groups work into non-invasive imaging research, predominately in echocardiograph, as well as Acute Coronary Syndrome / Percutaneous Coronary Intervention research.

The Cardiology Centre continues work on its Circulation Study proudly funded by a $200K research grant from the Ingham Institute. This study focuses on reviewing non-invasive imaging of the heart, as well as invasive imaging and interventions mainly in patients with recent heart attacks. Highly accurate information can be obtained on the status of patients with heart attacks, heart failure and arrhythmias in terms of early diagnosis, identification of aetiologies, risk stratification, and guidance of management including during late follow up.

Immune Tolerance Group leaders Associate Professor Suzanne J Hodgkinson and Professor Bruce M Hall and their team focus on T regulatory cells and how to enhance natural immune regulation mediated by these cells. Immunology Tolerance is a state where the immune system controls by self-regulating processes immune mediate inflammation.  These natural processes can prevent rejection of organ and bone marrow grafts as well as prevent or cure autoimmunity.  Autoimmune diseases affect up to 10% of the Australian population and include juvenile diabetes, multiple sclerosis, nephritis of the kidney, inflammatory bowel disease and many forms of arthritis.

The key mediator of immune tolerance is a specialized regulatory cell population that is known as CD4+CD25+T regulator cell (Treg).  This cell was first described by Professor Hall’s group in Australia and is now studied worldwide.   Therapy with this cells to prevent transplant rejection and cure juvenile diabetes is being trialled in the US and Europe.

The regulator cells can also have undesirable effects, preventing the immune system eliminating cancers and chronic infections.   New therapies that block their function, can lead to cancer cures.

The group’s work is very different to that done elsewhere.  Most studies examine a regulatory cell that inhibits all immune responses, our group studies cells that only suppress the unwanted immune response.  We can activate these specific cells in culture and transfer them to prevent rejection or autoimmunity in animal models.  The group has identified two pathways of activation of antigen specific Treg based on the novel cytokine receptor expression in rodent models.

We are now focussed on their comprehensive characterization and extending our animal work to humans, specifically how to activate antigen-specific T regulatory cells in culture and in the host.  We are also developing methods to monitor antigen specific T regulatory cells in patients.  We are focussing on therapy and monitoring for Multiple Sclerosis and organ transplants.   Studies are underway looking at these cells in Multiple Sclerosis and the newer therapies.

These studies are world leading and have major therapeutic potential in transplant rejection and autoimmunity.  Our cells are over 1000 fold more potent than those being tested overseas and are specific.  With adequate funding we could apply these findings to trials in therapy within a few years.   Hundreds of thousands of patients world-wide could benefit from such therapy.

The Dermatology Research Group is focused is on improving understanding of pathogenesis, diagnosis, and management of patients with dermatological disease.

The Dermatology Research Group has a specific research interest in autoinflammatory diseases such as hidradenitis suppurativa (HS), and psoriasis. Our work involves collaboration with local, national and international research groups as we strive for excellence in research that translates into improved patient care.

Our research team contributes to numerous peer-reviewed publications as well as presentation at local, national and international conferences.

 

Our current research areas include:

  • Nature and extent of inflammatory mediators in HS – in collaboration with Centenary Institute, Sydney
  • Polygenic nature of HS – in collaboration with Walter and Eliza Hall Institute, Melbourne
  • Optimal form of treatment algorithms for HS and complex Psoriasis.
  • Established investigation of the nature, incidence and treatment of Psoriatic Arthropathy – in collaboration with the Department of Rheumatology, Liverpool Hospital
  • Creation and maintenance of a biobank for research into complex Psoriasis and auto-inflammatory conditions
  • Investigation of the nature and component parts of the skin microbiome and its relationship with those dermatological disorders known or, suspected of being autoinflammatory – in collaboration with Monash University, Melbourne

 

Group leader: A/Professor Geoffrey Cains

Group: A/Professor Geoffrey Cains, Dr Dunja Vekic, Dr Jane Woods, Dr John Frew

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