The Department of Surgery at the Royal Melbourne Hospital, The University of Melbourne, has broad and diverse areas of interest in basic science, clinical research and education. The clinical research involves cardiovascular, anaesthesia, clinical ultrasound, prostate, general surgery and neurosurgery. The Royal Melbourne Hospital is one of the two trauma centres in the state of Victoria. The key focus of basic science laboratories relates to cancer and genetic research. The Department has an extensive online learning platform, and the Ultrasound Education Group (UEG) is one of the largest providers of clinical ultrasound training in the world. It is also a pioneer in simulator-based training which also includes the use of robots for surgery. The education platform is also the basis for the Mobile Learning Unit (MLU), which delivers continuing professional development training on behalf of the Melbourne Medical School and the Faculty of Medicine, Dentistry and Health Sciences (MDHS).
We are located within the educational and research hub known as the “Parkville Precinct”, allowing for strong linkages to other research institutions and internationally renowned groups.
The Academic Precinct Lead (Acting) at the Royal Melbourne Hospital, Department of Surgery is Professor Alistair Royse.
Professor Alistair Royse is a cardiothoracic surgeon and the acting head of the Royal Melbourne Hospital precinct.
He completed his general surgical training in 1992 and his cardiothoracic training in 1994. His MD thesis by research was in the field of complex total arterial coronary revascularisation. These strategies tried to achieve avoidance of any saphenous vein graft in coronary surgery and required numerous operative innovations and new techniques as well as the routine use of the radial artery from the forearm. Since 1997, the local coronary surgery practice is to avoid vein graft in approximately 85% of patients. From 1996, these techniques and strategies have led to very large-scale change which has persisted. Internationally, and elsewhere in Australia, the practice remains traditional, with 95% of patients who undergo coronary artery bypass surgery, receiving at least one saphenous vein graft. Large scale research by the group identifies a significant survival advantage for those who do not receive any saphenous vein graft.
He was also instrumental in the introduction of intraoperative echocardiography and epivascular ultrasound. He later was the foundational co-director of the Ultrasound Education Group (UEG) at the University of Melbourne. The first Diploma in clinical ultrasound was released in 2003, and the number of course participants, as well as the technologies used for the delivery platform, have increased exponentially. This has allowed tremendous scalability of education and is placing the University at the forefront of online learning capability. In response to the COVID-19 pandemic, eight courses were developed between late March 2020 and early May 2020, and more than 10,000 enrolments were received in this time.
Alistair was promoted to Professor by academic merit in 2012 and has been the Deputy Head of the Department of Surgery since 2013, and the acting head since 2019. He is also the co-director of the Ultrasound Education Group, the Melbourne Learning Unit, the Cardiovascular Research Group and a member of the Melbourne Medical School Executive Committee.
Key Research Areas
A diverse and wide-ranging interest in research reflects the large size and diverse nature of the members of this precinct:
- Arterial coronary bypass surgery (total arterial revascularisation)
- Radial artery as a conduit in coronary bypass surgery
- Tracking the progression and performing a definitive analysis of metastatic subclones of prostate cancer
- Improving glioblastoma diagnosis and treatment through identification and validation of serum biomarkers and understanding pro-tumorigenic properties.
- Phase 0 or “window of opportunity” clinical trials in glioma
- Brain oxygen neuromonitoring in severe head injury
- Standardising practice and access in neuroimaging to improve patient outcomes
- Molecular mechanisms of cerebral vasospasm after subarachnoid haemorrhage
- Identifying novel therapeutics for combating cancer cell invasion by targeting invadopodia
- Study of human pluripotent stem cells for modelling neurodegenerative diseases.
- Identifying the change in diagnosis and management of patients with point of care clinical ultrasound to assist examination and guide procedures.
- Measuring the educational benefit of using simulators and self-directed learning techniques for teaching skill-based workshops
- Investigating the use of focused cardiac and lung ultrasound and DVT scan in general medical patients with a cardiorespiratory diagnosis
- Dynamic TGF-β signalling regulation of tumour cell dissemination and tumour derived exosomes
- Treatment for Fuchs’ Endothelial Dystrophy (FED) without the need for traditional corneal transplantation.
- Safety and efficacy of multiple doses of IONIS-FB-LRX in patients with Geographic Atrophy secondary to Age-Related Macular Degeneration (AMD).
- Management and treatment of Phaeochromocytoma, Hyperparathyroidism, thyroid cancer and Graves Disease.
- Ultrasound Education Group
- Cardiothoracic Surgery
- Brain Tumour Biology and Therapies
- Stem Cell Disease Modelling
- Glioblastoma Survival Signaling Lab
- Prostate Cancer
- Cancer Signalling
- Brain Cancer Microenvironment and Biology Laboratory
- Breast Cancer
- Endocrine Surgery
Head of Research Group
The Ultrasound Education Group comprises of academics, including Prof Alistair Royse (Cardiothoracic surgeon, Deputy Director of Surgery), Prof Colin Royse (Anaesthetist), Dr David Canty (Anaesthetist, Senior Lecturer) and Dr Lindsay Bridgford (Emergency Physician, Academic), who supervise higher research degree students, undergraduate medical students performing research projects, and post-graduate clinicians pursuing active research and education projects.
Research themes include a wide range of ultrasound, including transoesophageal echocardiography for cardiac surgery, clinical point of care diagnostic ultrasound of heart, lungs, abdomen, vascular, invasive procedures, and new techniques. Other active areas of research include cardiac surgery, cardiothoracic anaesthesia, postoperative quality of recovery in all types of surgery, and medical education.
In 2015 the unit was successful in obtaining the largest NHMRC grant awarded to a department from The University of Melbourne, which was for The International Multi-Centre Randomised Trial on Transfusion Triggers in Cardiac Surgery, led from Ontario, Canada. In 2019 and 2020 there were successful Canadian and Australian grants for the TRICS-IV study, focusing on younger patients.
UEG develop and administer graduate courses in clinical ultrasound at a certificate, diploma or master’s level, which is well subscribed both within Australia and Internationally. The courses are unique in that they are very efficient, implementing a state-of-the-art online interactive eLearning software and platforms for both educational delivery as well as student enrolment, tracking and engagement.
In 2011, UEG received the Teaching Award for Excellence in Program Development with the Postgraduate courses in clinical ultrasound. Recently, the group has acquired high fidelity simulator equipment and set up a simulator education laboratory and education program, which is led by Dr David Canty, the Director of Simulation. A number of courses have been set up, which have been very successful amongst medical specialists, trainees and residents and are likely to change the way that practical ultrasound skills are learned. Details of the courses and workshops can be found at Ultrasound Education Group Courses
Head of Research Group
The cardiothoracic surgery unit performs all types of cardiac surgery and thoracic surgery. Operations at The Royal Melbourne Hospital as well as Melbourne Private Hospital. The multidisciplinary team includes surgeons, anaesthetists, perfusionists, intensive care and other associated specialties within the Royal Melbourne Hospital including cardiology oncology, radiation therapy and many more.
Across the two campuses, approximately 1100 cardiac surgery cases and approximately 400 thoracic surgery cases are performed.
Particular areas of interest:-
- Total arterial coronary artery bypass surgery
- Radial artery use as a coronary bypass conduit
- Sutureless aortic valve replacement
- Aortic aneurysm reconstruction
- The PEARS operation for aortic aneurysm
- Minimally invasive valve surgery
- Minimally invasive thoracic surgery
Head of Research Group
The research program undertaken in the Department of Surgery focuses on the biology and treatment of gliomas, the most common form of brain tumour and unfortunately, the deadliest. Grade IV glioma (glioblastoma multiforme or GBM) is the most aggressive of all and is highly invasive and often cannot be cured by surgery. Despite considerable research, treatment has not altered significantly, and the median survival remains at 9 - 12 months despite maximal safe resection, radiotherapy and chemotherapy.
Little is known about what causes brain tumours but we do know they have certain common genes that are either over-activated or mutated and these genes often encode growth factor proteins or other molecules that regulate the growth or invasion properties of the cell. Much of our research work is aimed at identifying the important genes, how they work together in pathways that lead to cancer, and where along these pathways, potential target molecules exist. Finding these effective targets has led to successful new drug therapies for breast cancer, renal cancer and leukaemia among others over the last decade, and much hope exists for the same to happen in brain tumour treatment. Additionally, we are looking into better ways to test for and monitor brain tumour treatment, as
well as the mechanisms of why seizures occur.
Importantly our interdisciplinary research team has established a large brain tumour bank of archived tumour tissue and patient serum/plasma. We have also established a large library of patient-derived glioma organoids. These unique research tools are at the forefront of our collective research efforts.
Specifically, our research team is exploring several research areas concurrently, with the overarching aim of improving glioblastoma diagnosis and treatment. These areas of research include:
1. Identification and validation of serum biomarkers that can predict the presence of glioblastoma, recurrence of glioblastoma post-treatment and the efficacy of standard and novel treatments.
2. Furthering our understanding of the pro-tumorigenic properties of glioblastoma, including the molecular mechanisms used by these tumours to survive and continue to proliferate in sub-optimal environments and invade surrounding areas of the brain.
3. Pre-clinical testing of re-purposed and novel agents against several glioblastoma specific in vitro and in vivo models.
The Department of Neurosurgery at the Royal Melbourne Hospital is the busiest neurosurgical unit in Australia, sitting in the heart of the Parkville Biomedical precinct, and provides a comprehensive inpatient service for patients with neurosurgical diseases, with a clinical and referral service for patients with intracranial, spinal and peripheral nerve disorders requiring neurosurgical assessment and treatment.
Our lab focuses on brain tumours and epilepsy. We aim to understand the neurobiology of brain tumours, particularly glioma. Our current major project is discovering new blood-based biomarkers for glioma diagnosis and monitoring using microRNA and DNA. We also focus on understanding the role of glioma stem cells and their underlying genotypes in progression of glioma and using stem cell organoid cultures as a basis for discovering new molecular-targeted treatments for glioma. We also work on the neuroscience behind how brain tumours cause epileptic seizures and have published on the role that the glutamate neurotransmitters play.
We collaborate closely with the neurosurgery and neuro-oncology services at The Royal Melbourne Hospital where we are involved in clinical trials in neuro-oncology patients. We have close researcher collaborations around the Parkville Precinct including the WEHI, VCCC/Peter MacCallum Cancer Institute and the Florey. We also work in collaboration with international experts in Israel, the UK and Toronto, Canada.
The Department is one of the few genuinely academic Neurosurgery Departments in Australasia. It has active clinical and laboratory research programs that augment each of the clinical specialised programs undertaken by the Department alone and in conjunction with the Departments of Neurology, Radiology and Oncology. Data and tissue collection are central to the work of the Department. Most clinical programs are involved with national and international clinical trials. The specialised clinical programs include: Brain Tumours, Cerebrovascular Surgery, Spinal Disorders, Neurotrauma, Neuro-endocrinology, Epilepsy and Functional and Pain Neurosurgery. The Department has an active research, fellowship and teaching program at both an undergraduate and postgraduate level for medical, nursing and allied health staff. Enquiries for fellowships in Neuro-Oncology and Spinal Surgery are welcomed as are enquiries for PhD supervision.
Head of Research Group
Research Overview Our laboratory focuses on the study of human pluripotent stem cells for modelling neurodegenerative diseases.
The difficulty in obtaining brain or ocular tissue from living people is a major barrier to developing new treatments for neurodegenerative disease. We can now generate stem cells from adult tissue, and these “induced pluripotent stem cells” (iPSCs) represent a powerful disease modelling tool. Generating iPSCs directly from patients allows cells to be differentiated into specific cells of interest for disease modelling, drug screening, and understanding of fundamental pathogenic mechanisms.
We differentiate iPSCs into various cell types of the nervous system, as monolayers or as organoids. Using these cells, we model age-related macular degeneration, glaucoma, inherited retinal dystrophies and optic neuropathies, in order to establish the molecular events leading to disease progression and aspects of neurodegeneration. We also use gene editing technology for the correction of monogenic diseases of the retina and the optic nerve.
Head of Research Group
Our lab aims to understand how cancer signaling molecules and pathways regulate the pro-tumorigenic characteristics of glioblastoma, the most aggressive and lethal brain tumour in adults. Along with being highly proliferative and invasive, glioblastoma cells are also capable of surviving in sub-optimal conditions such as nutrient and oxygen-poor environments. However, the exact signaling pathways used by glioblastoma cells to tolerate and survive these sub-optimal conditions are not completely known. Recently, our lab has begun to elucidate the signaling pathways that promote cell survival when cells are in low nutrient or oxygen conditions. Specifically, we have identified a novel growth factor and cytokine-dependent mechanism that promotes glioblastoma survival. Using primary patient-derived glioblastoma cells; we have uncovered a novel signaling network involving the activation of the glutamine metabolic pathway under glucose-starved conditions. This glutamine metabolic pathway protects glioblastoma cells from cell death by inhibiting endoplasmic reticulum stress mediated apoptosis thereby providing glioblastoma cells with a survival advantage over cells that do not utilise this novel signaling cascade. Importantly, these discoveries provide rationale for targeting the glutamine metabolic pathway as a therapeutic approach in glioblastoma. Our current research will expand on these findings with our over-arching hypothesis that glioblastoma cells drive enhanced glutamine metabolism leading to reduced ER stress, reduced ER-mitochondrial interaction, reduced mitochondrial Ca2+ uptake and increased glioblastoma cell survival.
Head of Research Group
Research Overview The Prostate research group is focused on :
- Deciphering the genomic drivers of metastatic potential in prostate cancer
- Tracking the dissemination of cancer cells from the primary organ to distant sites
- iTo further the clinical translation of a small molecule that targets the Tau protein in the brain to treat neurodegenerative diseases.
- Developing tissue and blood tests that will predict future risk of progression in men at the time of diagnosis
- Developing new ‘curative’ treatments in patients with high risk disease
- Developing new tests that will predict how patients will respond to treatment
Our work over the past five years has placed our group in a pivotal position to decipher the genomic codes that drive metastasis and lethal disease in prostate cancer. We have established and lead a team of researchers with unique expertise in tracking, sampling and interrogating, with deep genomic analyses, lethal prostate cancer specimens in living patients. These analyses have revealed for the first time, the precise patterns and direction of lethal metastatic spread, as well as determined the tumour complexity at primary and metastatic sites.
Our ongoing work aims to directly assess the prognostic potential of the metastatic signatures by linking genomic signatures to clinical outcomes, potentially having a transformative effect on clinical prognosis in prostate cancer.
Our group is also one of the founding members of the Pan Prostate Cancer Group (PPCG), an international consortium which has created the largest tumour specific genome database yet assembled. The PPCG is collecting and interrogating Whole Genome DNA Sequence and exome data generated around the world from over 2000 men with prostate cancer, including men from different clinical categories, and ethnicities. To date over 1800 whole genomes have already been assembled and alignment and initial processing using common analysis pipelines has already completed. This now represents the largest tumour specific data set ever assembled. Most importantly and unlike any other large international tumour sequencing project, the PPCG will have long term and ongoing clinical follow up of all patients enrolled in the project. Hence, for the first time, tumour-specific genetic variations will be able to be matched with meaningful clinical outcomes and endpoints, and the scale of the project will ensure it has the power to uncover clinically meaningful tumour signatures. The Prostate Group is one of the co-founders of the Consortium and was also chosen to lead the task group focusing on advanced and metastatic disease within the Consortium.
Our laboratory has also had a longstanding basic discovery science program which has spanned interests of tumour biology and neuroscience. This has led to the discovery and patenting of a small molecule that targets one of the potential underlying causes of neurodegeneration in the brain. We have successfully translated this molecule, sodium selenate, into firstly the commercial and then the clinical spheres in multiple clinical trials, led by our brilliant collaborators Prof Terry O’Brien and Prof Dennis Velakoulis, which are now yielding highly encouraging signals of targeted efficacy in early Phase II
Head of Research Group
Dr Hong-Jian Zhu’s research focuses on disruption of the fundamental molecular pathways, particularly the Transforming Growth Factor (TGF-beta) signalling during cancer development with specific advance on the field of the newest bioactive microvesicles, exosomes.
Head of Research Group
Our research goal is to understand the molecular and cellular biology of brain cancer.
One of our key research areas is to investigate the brain tumour microenvironment.
To successfully manage difficult-to-treat cancers, such as brain cancer, both the cancer cells and the non-cancer cells within the tumour tissue, including tumour infiltrating immune cells must be considered. In brain cancer one of the phenomena which must be overcome for successful treatment is tumour-specific immunosuppression. This immunosuppression blocks the body’s own immune system or immunotherapies from killing the cancer cells.
We are exploring how the cancer cells and tumour immune cells cooperate to establish immunosuppression. To do this, we use state-of-the-art microscopy and computational biology to map brain tumours to identify the cells and the factors, which control tumour immunosuppression (see image below). This research will allow us to understand how to modulate the tumour and immune system to provide long-term control of brain tumour growth, to ultimately transform deadly brain cancers into manageable chronic diseases.
We have also developed a genetically engineered mouse model in which we can mimic human brain tumour development. Using these mice, we can trigger brain cancer at different ages to model specific human brain tumour types and to test novel therapies, which can then be moved to clinical trials in patients.
Head of Research Group
Dr Skandarahah's main research interests are clinical trials into tailored treatments in early breast cancer, prevention and screening of patients at high risk of developing breast and endocrine malignancies and outcomes in emergency general surgery.
Key research areas:
- Value-based outcomes research in surgery
- Patient reported outcomes after breast cancer surgery and risk-reducing surgery
- De-escalation of therapies after cancer diagnosis
We established the surgeon-led Emergency General Surgical service at The Royal Melbourne Hospital in 2011 and set up a clinical database, which was autopopulated from the admission episode system (iPM) from our institution. The database has been built to be flexible to capture morbidity and mortality in real-time and to validate admission diagnoses, operations and complications. Projects include outcomes after Emergency General Surgery comparing a new model of care to an older established care of surgical patients was the largest study at the time evaluating over 7000 patients and showed a 47% reduction in mortality and 56% decrease in mortality. Other completed studies evaluated the impact on the management of acute biliary disease, liver trauma, trauma in pregnancy.
Administrative data is routinely collected on all patients who are admitted to a hospital in Australia. Patient demographics, diagnosis, length of stay, procedures and complications are all captured in this fashion. Built for the purpose of billing, it also offers a unique opportunity to be used for the purpose of clinical outcomes research. The strength of administrative data as a research tool is its extremely large numbers, low cost and completeness. We have used various platforms for data linkage and have enabled comparative projects such as international variation in management and morbidity and mortality after acute diverticultis and colorectal cancer resection and using administrative data to act as surrogates for cancer databases.
De-escalation of therapies of low value after breast cancer is a focus of our work and we focus our research on clinical trials to evaluate this. The PROSPECT (Post-operative Omission of Radiotherapy after Early Breast Cancer) has completed accrual.
Endocrine Surgery involves clinical management of patients suffering from tumours of the endocrine system, including:
- Benign and malignant tumours of the thyroid gland.
- Primary hyperparathyroidism
- Adrenal tumours, including phaeochromyctoma
- Familial endocrine tumour syndromes such as Multiple Endocrine Neoplasia.
Recent completed projects:
- Maternal and Foetal Outcomes in Pheochromocytoma and Pregnancy.
- Bi-national review of phaeochromocytoma care. Is ICU admission always necessary?
- Adrenalectomy for Phaeochromocytoma: a 17-year review of surgical technique and outcomes
- Clinical Utility of Routine Parathyroid Hormone Measurement in Women Commenced on Endocrine Therapy for Hormone Sensitive Breast Cancer.
- Radioactive Iodine Ablation post Differentiated Thyroid Cancer Surgery: an Analysis of Use and Impact of the ATA Guidelines.
- Massive Spontaneous Cervico-mediastinal Haemorrhage from a Parathyroid Adenoma
- Practice Patterns in Parathyroid Surgery: A Survey of Asia-Pacific Parathyroid Surgeons.
- Imaging Strategies in Primary Hyperparathyroidism
- Development of a Bi-National Thyroid Cancer Clinical Quality Registry.
- Surgical Management of Graves’ Disease – A Contemporary Perspective.
Head of Research Group
Descemetorhexis Without Endothelial Keratoplasty (DWEK)
This study evaluates the possibility of removing a section of Descemet’s membrane along with its diseased endothelial cells, without corneal transplantation, and simply leaving the cornea to heal on its own, as a new treatment for Fuchs’ Endothelial Dystrophy (FED). This procedure is known as ‘Descemetorhexis Without Endothelial Keratoplasty (DWEK)’ or ‘Descemet’s stripping only (DSO)’. DWEK/DSO may improve vision in persons with FED without the need for traditional corneal transplantation.
Keratoconus International Consortium (KIC)
International collaborative study to evaluate Keratoconus.
RMH Ophthalmology Clinical Trials
A Phase 2, randomised, placebo-controlled, double-masked study to assess safety and efficacy of multiple doses of IONIS-FB-LRX, an antisense inhibitor of Complement Factor B, in patients with Geographic Atrophy secondary to Age-Related Macular Degeneration (AMD).
Laboratory Facilities at Department of Surgery, Victorian Comprehensive Cancer Centre (VCCC)
Executive Assistant to Professor Alistair Royse
Ph: +61 3 8344 2033 / +61 3 8344 5492
Dr Hong-Jian Zhu
Ph: +61 3 8344 3025
Graduate Research Programs Coordinator
Ph: +61 3 8344 3296
Royal Melbourne Hospital,
Centre for Medical Research building
Level 6 / 300 Grattan St, Parkville