Awarded Project grants

Project grants awarded 2016

  • 06 Dec 2016

SECONDARY LYMPHOEDEMA ($159,994 – 2 years) 1116012

Dr Jonathan Astin
Dept. of Molecular Medicine & Pathology, University of Auckland

The lymphatic vasculature plays an essential role in fluid homeostasis; it collects excess interstitial fluid and returns it to the bloodstream. Lymphatic vessel dysfunction leads to the painful and debilitating build-up of fluid in the body, termed lymphoedema. Secondary lymphoedema can occur when lymphatic vessels are damaged following the surgical removal of lymph nodes in cancer patients and it is one of the most significant survivorship issues following surgical or radiological treatment of tumours, particularly breast cancer. In New Zealand, 20% of women who undergo axillary lymph node removal and/or radiotherapy as part of treatment for breast cancer will develop secondary lymphoedema. There is no definitive cure for secondary lymphoedema and symptoms are managed through the wearing of compression garments, lifestyle changes and surgical removal of tissue. Consequently, there is considerable interest in therapies that stimulate lymphatic vessel repair to help prevent lymphoedema. However, we know very little about how lymphatic vessels regenerate following injury. In this project we will develop new models of lymphatic vessel repair and use these to identify the mechanisms and genes involved in lymphatic regeneration. This work will be an important first step in the development of new therapies in the prevention of secondary lymphoedema.



Dr Doug Campbell, Dr Tom Burrows, Dr Cornelius Kruger, A/Prof Timothy Short
Dept. of Anaesthesia, Auckland District Health Board

Atrial fibrillation is an abnormal heart rhythm, which is common in older people. It is associated with increased risk of stroke, which can have devastating consequences. Patients who have episodes of atrial fibrillation frequently receive anticoagulant medicines (such as warfarin) to reduce the risk of stroke. After surgery, it is common for older patients to have an episode of atrial fibrillation. We do not know how commonly this occurs, or what the consequences are. The Perioperative Atrial Fibrillation and Postoperative Stroke (PAFS) study will determine the incidence and consequences of atrial fibrillation after surgery. Patients will wear a heart monitor before surgery, and for two weeks after surgery. They will undergo MRI scan of their brain several days after surgery looking for any evidence that they have had a small stroke. This study will be performed across several hospitals internationally, including Auckland City Hospital. The PAFS study might change how we treat patients who have an episode of atrial fibrillation after an operation, in order to protect them from complications such as stroke.

FUNDED BY: AC Horton Estate



Prof Larry Chamley, Dr Scott Graham
Dept. of Obstetrics & Gynaecology, University of Auckland

Extracellular vesicles are part of an elaborate system that the fetus uses to control maternal blood pressure as well as, the maternal immune system during pregnancy. Antiphospholipid antibodies are found in some women and cause still-births and recurrent miscarriages. These antibodies also increase the chance that a woman will develop potentially fatal high blood pressure during pregnancy. We have previously shown that antiphospholipid antibodies can change the nature of placental vesicles such that they might cause increased blood pressure and other complications of pregnancy. In this study we will examine the maternal organs, and the cells within those organs, that placental vesicles target. We will also investigate whether treating placentas with antiphospholipid antibodies alters which maternal organs placental vesicles target to. This research will help us to understand how the fetus controls its mother’s physiological systems by targeting specific maternal organs to allow normal pregnancies and whether inappropriate targeting of placental vesicles causes diseases of pregnancy.



Dr Juliette Cheyne, Prof Peter Thorne, A/Prof Johanna Montgomery
Dept. of Physiology & Centre for Brain Research, University of Auckland

Autism Spectrum Disorders (ASD) are developmental disorders defined by learning difficulties, sensory issues, communication difficulties, social deficits and stereotyped behaviours. Because ASD symptoms appear during infancy, it is crucial to examine how brain development is altered, as this could cause behavioural deficits. The social and communication difficulties in ASD are thought to be due to abnormalities in the processing of sounds, which in turn impairs language abilities. We hypothesise that this impaired sound processing is due to connections between brain cells in the auditory cortex forming incorrectly during development. We will utilise state-of-the-art cellular recording techniques in live mice to determine how the development of the auditory cortex is affected in ASD. We will reveal developmental differences in brain activity in ASD mice, which could lead to deficits later in life. We will also determine whether cortical organisation of tones (from high to low frequency) and plasticity in the auditory cortex are altered in ASD mice. The information obtained in this study is essential to advance knowledge of how changes in the activity in the developing brain link to deficits in sensory processing later in life, which could also be relevant to other neurodevelopmental disorders.


OVERCOMING DRUG-RESISTANT BACTERIA ($154,847 – 2 years) 1116001

A/Prof Brent Copp, Prof Jean Michel Brunel, Dr Siouxsie Wiles
School of Chemical Sciences, University of Auckland

For several decades the routine use of antibiotics has saved countless lives. Recently, the World Health Organisation described how antibiotic-resistant bacteria are present in every region of the world, including New Zealand, and called for drastic action to prevent a return to the pre-antibiotic era. New antibiotics are needed, or alternatively, new methods are needed to restore the activity of antibiotics against drug-resistant bacteria. We have recently discovered a class of compounds that do the latter – enhancing the activity of the antibiotic doxycycline towards the normally drug resistant bacterium Pseudomonas aeruginosa. This project involves the synthesis and biological evaluations of new molecules based around our discovery, where we will optimize the antibiotic enhancing activity of this compound class and determine how such enhancement is achieved. This will provide proof of concept as to whether such compounds can be used to ‘rehabilitate’ old antibiotics, and to thereby restore their effectiveness to aid in the fight against drug-resistant bacterial infections.


IGF-1 AND PRETERM BRAIN INJURY ($158,997 – 2 years) 1116008

Dr Justin Dean, Prof Alistair Gunn
Dept. of Physiology, University of Auckland

In New Zealand, approximately 500 babies are born prematurely every year, and around half survive with life-long disabilities. These disabilities often result from infection and inflammation around the time of birth. Excitingly, we now know that the brains of preterm babies can recover rapidly from injury, but may then fail to develop normally. Using a new rodent model of very preterm brain injury, we found that inflammation can impair normal brain development. Further this was associated with a reduction in the levels of insulin-like growth factor (IGF-1), a molecule critical for normal brain growth. In this proposal, we will test whether restoring normal levels of IGF-1 in the brain during or after infection will promote brain maturation, and thus restore normal brain development. We will compare direct treatment of the brain using IGF-1 with an agent that can improve availability of locally produced IGF-1.

FUNDED BY: NR Thompson Trust



Prof Mark Elwood, Prof Ross Lawrenson, Dr Sandar Tin Tin, A/Prof Vernon Harvey, A/Prof Ian Campbell
Epidemiology and Biostatistics, School of Population Health, University of Auckland

This project will develop and assess methods to predict future outcome for women treated for breast cancer. We will use the information in the combined Auckland-Waikato breast cancer registries, provided by over 7000 women with at least 5 years’ follow up from diagnosis; we will develop a New Zealand-specific system to predict breast cancer outcomes, and compare its performance with existing methods, which have all been developed overseas. Such a model will use data collected routinely in current clinical practice, and will be applicable to individual patients, particularly to identify those with likely very good or very poor outcomes.

FUNDED BY: Hugh Green Fund



Dr Peter Freestone, Prof Janusz Lipski
Dept. of Physiology, University of Auckland

The chemical transmitter dopamine underlies many of our basic behaviours, including movement. However, the exact mechanism determining the timing and magnitude of dopamine release in the brain remain unknown, limiting our ability to effectively treat diseases in which dopamine release is affected, such as Parkinson’s disease. I recently discovered that a unique cannabis-like substance produced in the brain (an endocannabinoid) – NADA – can alter the activity of dopamine-producing cells. This particular endocannabinoid is of great interest as it shares a common biosynthesis pathway with dopamine and is therefore of high importance to the pathophysiology of Parkinson’s disease. The current study will use advanced dopamine-detection (electrochemistry) and cell-type specific stimulation (optogenetics) techniques that are ideally suited to studying the complex network underlying dopamine release. These approaches will establish the mechanism by which NADA controls dopamine levels and related movement behaviours. A range of experimental models from living brain slices to freely moving animals will be used to provide a robust translational investigation. The findings will determine whether the NADA-based mechanism is a suitable target for new therapeutic strategies for diseases like Parkinson’s disease – “The saddest of diseases” (James Parkinson 1817).


CB1 IN BRAIN CANCER ($157,272 – 2 years) 1116011

A/Prof Michelle Glass, Dr Scott Graham, Dr Graeme Finlay
Dept. of Pharmacology & Clinical Pharmacology, University of Auckland

While there is a public perception that cannabis might cure cancer, the scientific evidence far from clear cut. Cannabis itself is made up of a number of different compounds, but the key psychoactive ingredient targets a receptor in the brain called CB1. CB1 has been under investigation for a number of years as a possible therapeutic target, and there are now many compounds available that can activate or inhibit this receptor. In studies investigating cannabinoid ligands that target the cannabinoid receptors in cancer cells the outcome has been quite mixed, with some reports of tumour cell death, but others that have observed an increase in cell proliferation. We have some evidence to suggest that the level of cannabinoid CB1 receptors expressed in cells influences the signal that is produced by activation of the receptors – and hypothesize that this observation is the reason for the diverse findings in the field. Here we aim to utilise human brain cancer cells to investigate if the expression and function of cannabinoid receptors in these cells and determine if CB1 receptors are a valid therapeutic target.

FUNDED BY: Pauline Gapper Charitable Trust


INVESTIGATION OF TRIM28-KRAB INTERACTIONS ($158,200 – 2 years) 1116014

Dr David Goldstone
School of Biological Sciences, University of Auckland

Mammalian genomes are littered with the remains of previous retroviral infections. During the early stages of development these retroviral sequences are potently and permanently silenced prevent the expression of retroviral genes. This silencing accompanies the wave of differentiation that alters transcription during normal development and acts to shape the genes that are expressed in particular cells. Trim28, a member of the tripartite motif protein family, is the central player is this control and as such has been labelled the master regulator of the human genome. More recently Trim28 has been implicated in cancer and diabetes and obesity. We aim to understand the molecular details that target Trim28 to particular sites within the genome resulting in the silencing of particular genes. This research will lay the foundation to manipulating this system to alter transcription and treat diverse medical diseases.



A/Prof Nuala Helsby, Dr Frederik Pruijn, Dr Matthew Strother, Prof Michael Findlay
Dept. of Molecular Medicine & Pathology, University of Auckland

Some cancer patients who are treated with 5-FU, and other related drugs, have an increased chance of treatment failure due to high expression of the drug target (thymidylate synthase). An inherited risk for poor treatment outcome has been reported in a number of studies. It is possible to look at a patients DNA to see if they have this thymidylate synthase gene variant. But currently when these individuals are identified there is no clear way to decide how to safely and appropriately increase the drug dose. Our project will assess a method of monitoring effective 5-FU concentrations at the drug target in the cell. We want to adapt and improve the method using a technique called targeted peptide analysis. If this test is sensitive, accurate and reproducible enough we may then be able to use this approach to help oncologists to improve the safe and effective use of this drug especially in those people who may have inherited a resistance to this type of treatment.

FUNDED BY: Anonymous Donor


AUGMENT REALITY AIDED LIVER ABLATION ($110,139 – 2 years) 1116020

Dr Harvey Ho, Dr Peter Swan, Dr Adam Bartlett, A/Prof Andrew Holden
Auckland Bioengineering Institute, University of Auckland

Minimally invasive procedures provide a real alternative to surgical resection for small tumours. Success of the technique depends largely on the accuracy of ablation probe placement for killing tumour cells in-situ, while also limiting damage to healthy tissue. However, 2D ultrasound image based guidance of a probe, as used in current clinical practice, does not provide precise 3D information of the probe tip, therefore the errors need be corrected to have an optimal operational outcome. We propose to develop an Augmented Reality aided navigation system which is delivered through a Head Mounted Display (HMD). We aim to accomplish four tasks over a two-year timeframe: (1) To develop a vision-driven abdominal model incorporating respiration effects; (2) To integrate data from vision and motion sensors for improved accuracy of probe placement; (3) To implement an Augmented Reality environment delivered through a HMD; and (4) To validate the algorithms using a 4D ultrasonic scanner and an abdominal phantom. Successful implementation of the workflow will not only lead to new methods for precise positioning of ablation probes, but will also establish cornerstones for the use of Augmented Reality in a clinical environment in New Zealand.

FUNDED BY: W & WAR Fraser Charitable Trust


NIVORAD ($104,454 – 2 years) 2116019

Dr Louis Lao, Dr George Laking
Radiation Oncology, Auckland District Health Board

This study aims to evaluate whether addition of stereotactic radiotherapy provides additional benefit in patients who are treated with immunotherapy (nivolumab) for advanced lung cancer. Immunotherapy is a treatment which helps a person’s immune system to fight cancer. Nivolumab have generated a lot of interest recently having made major breakthroughs in cancer patients. Stereotactic radiotherapy is a type of radiotherapy where very large doses are given very precisely. While radiotherapy has been used as a cancer therapy for a long time, there is now interest in the idea that radiotherapy can have immunological effects and that it can enhance the effects of immunotherapy. This study will look at this new treatment concept of combining immunotherapy with stereotactic radiotherapy to better understand its effectiveness and also safety. Both immunotherapy and stereotactic ablative radiotherapy are state of the art cancer treatments which have changed the landscape of cancer treatment in recent years. In New Zealand, access to these types of treatment is limited. This study will allow New Zealand patients access to these types of treatment and help to answer an important scientific question which potentially will translate into a new treatment paradigm which will help to improve patient’s outcomes.

FUNDED BY: Anonymous Donor



Dr Julie Lim, Prof Paul Donaldson, Dr Monica Acosta
Dept. of Physiology, University of Auckland

With advancing age, oxidative stress results in redox imbalance and eye diseases which threaten the sight of the elderly. We propose that the cystine/glutamate antiporter (CGAP) in the eye is important for maintaining redox balance and minimising oxidative stress. Clinical assessments on CGAP knockout mice reveal the early onset of eye diseases. To elucidate the underlying pathways that result in these pathologies, molecular and functional tests will be performed and this information used to guide the design of effective therapies that target a specific tissue of the eye against oxidative stress to delay the onset of age related eye diseases.

FUNDED BY: John Jarrett Trust



Dr Rinki Murphy, Ms Naomi Davies, Dr Justin O’Sullivan, A/Prof Lindsay Plank
Dept. of Medicine, University of Auckland

The prevalence of diabetes has reached epidemic proportions in New Zealand, with reported prevalence at 7% among adults. Bariatric surgery is currently the only therapy with long-term weight reduction and dramatic effects on both remission and prevention of type 2 diabetes among those with severe obesity. Currently, the most improved rates of diabetes remission are being reported in patients receiving gastric bypass (GBP) compared to sleeve gastrectomy (SG). Therefore, understanding the mechanisms underlying the distinct and common impacts of GBP over SG in achieving type 2 diabetes remission and sustained weight loss is important for developing novel medical treatments. Gut hormones and microbiota, are emerging as novel mediators of obesity and type 2 diabetes. They play a key role in dietary energy extraction, hunger stimulation, inflammation, glucose metabolism and improved metabolic outcomes. This research aims to determine how the two main bariatric surgery procedures, GBP and SG, induce changes in gut microbiota, how these changes relate to the fluctuation of gut hormones, and how this differs between the contrasting surgeries. This work has the potential to identify novel probiotics or a gut microbiota transplant strategy for management of obese patients with type 2 diabetes to complement or replace surgery.



Dr Max Petrov, Dr Rinki Murphy
Dept. of Surgery, University of Auckland

The project aims to define new onset diabetes after diseases of the exocrine pancreas, more specifically acute pancreatitis, and to characterise its underlying hormonal profile. One of the key objectives is to test the hypothesis that a blunted pancreatic polypeptide response to a mixed-nutrient meal test is a specific marker of diabetes after acute pancreatitis (compared to type 2 diabetes mellitus). Additionally, we seek to characterise patterns of insulin secretion and resistance as well as gut hormonal (incretin) response in these two diabetes subtypes (type 2 diabetes mellitus and diabetes after acute pancreatitis). It is envisaged that data generated from this project will enable earlier diagnosis and better treatments for diabetes after diseases of the exocrine pancreas, for which there are no specific guideline recommendations.

FUNDED BY: Marion Ross Memorial Fund



Dr Anna Ponnampalam, Prof Cynthia Farquhar
Liggins Institute, University of Auckland

Endometriosis is characterised by the presence and growth of endometrium (the lining of the uterus) outside the uterus. It is a common cause of infertility and chronic abdominal pain in reproductive age women. While the incidence is approximately 10%, the actual prevalence is much higher because many women and girls are initially misdiagnosed. Endometriosis-related pain is serious, debilitating and episodic. Current treatment modalities have major limitations and are only successful in half the patients and these women generally develop resistance to repeated treatments with the same agent over a period of 6 months to 3 years. Hence the clear need to identify novel molecular pathways that can provide early identification of developing resistance, inform current therapies and enable future targeted therapy development. The project is to test the hypothesis that DNA methylation plays a crucial role in the aberrant oestrogen priming of the endometrium that lead to progesterone resistance and development of endometriosis. The overall objective of this project is to understand the mechanisms involved in progesterone resistance generally seen in endometriosis, thereby improving identification and potentially enabling the development of effective therapeutic interventions.



Dr Fiona Radcliff, A/Prof Thomas Proft
Dept. of Molecular Medicine & Pathology, University of Auckland

Effective delivery of approved vaccines typically requires qualified personnel, defined storage conditions and injection of the materials. Using live organisms, such as food grade bacteria, for vaccine production and needle-free delivery (e.g. by ingestion) is a promising alternative. A novel vaccine delivery vehicle, called PilVax, has been developed by researchers at the University of Auckland. The basis of PilVax is a bacterium found in yoghurt, called Lactococcus lactis, which has been modified to express large quantities of foreign proteins including vaccine candidate antigens, on its surface. Preliminary studies in mice have shown that delivery of PilVax into the nasal cavity can indeed stimulate robust immune responses. The goal of this project is to build on that work by testing whether PilVax mediated delivery of vaccine candidate antigens from Staphylococcus aureus, an important bacterial pathogen that is very common in New Zealand, can stimulate protective immunity to this pathogen. If PilVax proves to be effective in these tests it will establish this delivery platform as a promising and flexible approach for non-invasive vaccination against not only S. aureus but also other mucosal pathogens.

FUNDED BY: John and Poppy Stilson Endowment Trust



Dr Veronika Sander, A/Prof Alan Davidson, Dr Rinki Murphy
Dept. of Molecular Medicine & Pathology, University of Auckland

Kidney disease is a serious problem in New Zealand, particularly amongst the Māori and Pacific people. Cystic kidney disease is common and is associated with the progressive growth of fluid-filled cysts that can eventually cause kidney failure. Mutations in the HNF1B gene, which acts as a ‘master switch’ for many other kidney genes, are responsible for cyst formation but the molecular pathways operating downstream of HNF1B are poorly understood. Furthermore, there is no good way to study human kidney cyst formation in the laboratory. We have established state-of-the-art strategies that allow us to grow human kidney organoids (cultured mini kidneys) and introduce HNF1B mutations into these cells. This novel approach provides a new tool to study kidney cyst formation and, in future applications, will enable new drugs to be tested.



Dr Giuseppe Sasso, Dr Shankar Siva, Mrs Rebecca Montgomery
Radiation Oncology, Auckland District Health Board

Stereotactic ablative body radiotherapy (SABR) is a high-precision, non-invasive and low-toxicity alternative for treatment of small lung lesion. Due to early reports of excellent control rates (comparable to surgery) and minimal associated toxicities, SABR is being rapidly implemented worldwide and in New Zealand in the treatment of small peripheral lung lesions. Approximately 30% of all cancer patients will develop secondary spread to the lung during the course of their disease. In patients with limited secondary cancer in the lung, SABR can result in long-term survival and even cure. As it is non-invasive, delivered in as little as a single outpatient visit and without the need for hospitalisation, SABR is an attractive and potentially very cost-effective treatment option. Additionally, emerging evidence suggests that large doses of precision SABR may evoke a strong immune response to recognise and attack remaining tumour cells in the body. SAFRON II is a randomised phase II clinical trial comparing single treatment versus multi-treatment SABR techniques (i.e. 4 fractions). This research will be the first comprehensive evaluation of SABR techniques integrating the assessment of (1) clinical outcomes, (2) quality of life (3) cost-efficacy and (4) translational immunological investigation.


EPIGENETIC TARGETING OF METASTASIS ($106,725 – 2 years) 1116002

Dr Dean Singleton, A/Prof Adam Patterson
Auckland Cancer Society Research Centre, University of Auckland

Breast cancer is the most common cancer in New Zealand women accounting for nearly 3000 new registrations and over 600 deaths each year. Although breast cancer outcomes are improving with earlier detection and more effective treatments, most patients die when their cancers spread (metastasize) into secondary organs. The blood vessels that supply breast tumours are poorly developed and are unable to deliver sufficient oxygen to the tumour. This results in regions of low oxygen (hypoxia) forming within the tumour. Hypoxia is critically important because it causes cancer cells to become more invasive, resulting in an increased risk of metastasis and poorer patient survival. This occurs because certain enzymes sense low oxygen and respond by switching on genes that promote invasion. We are developing new drugs to target these changes. In this work we will investigate the potential of these drugs to prevent hypoxia signalling in tumour models and reduce tumour growth and metastasis. The results of this study will help to develop effective strategies to prevent cancer metastasis and improve patient survival.

FUNDED BY: Anonymous Donor



Dr Clinton Turner, Prof Mike Dragunow, A/Prof Maurice Curtis
Anatomical Pathology, Auckland District Health Board

Meningiomas are tumours of the covering layer (the dura) of the central nervous system. In New Zealand it has been reported that these tumours disproportionately affect Maori and Pacific Island women – who appear to get meningiomas at a younger age and have tumours that are larger in size than Caucasians. While the majority of meningiomas are “benign”, they may still cause significant harm by growing in critical locations or surgically inaccessible sites thereby preventing complete removal. Some meningiomas may also repeatedly reoccur necessitating repeated surgical intervention and/or radiotherapy. Compared to many other tumours, meningioma research is a relatively neglected area. The role of the immune system has been widely investigated in a variety of tumours (e.g. melanoma, breast cancer). This has resulted in the realisation that the tumour-associated immune cell infiltrate is often highly prognostically significant. The goal of this research is to examine whether the composition and density of the immune cell infiltrate in meningioma is prognostically significant in predicting tumour recurrence. This will potentially help improve the ability of the pathologist to predict tumour behaviour for an individual patient. It may also open up further research avenues into immune-modifying therapies in meningioma.


miRNAS AS EARLY PREDICTORS OF PRETERM BIRTH ($114,379 – 2 years) 1116010

A/Prof Mark Vickers, Prof Lesley McCowan, Dr Katie Groom, Dr Clint Gray
Liggins Institute, University of Auckland

At a global level, more than one in 10 babies are born too early (<37 weeks of pregnancy) equating to over 15 million preterm births and more than one million new-born deaths. Preterm birth also increases the risk of death due to other causes including neonatal infections. In New Zealand, nearly 8% of babies are born preterm and, of those, approximately 60% occur after spontaneous onset of labour. Preterm birth rates are higher in Maori women at around 14%. Although women with a previous spontaneous preterm birth (SPTB) are considered to be at high risk for recurrence, the majority occur in women without prior history. Accurate prediction of SPTB risk, before the clinical event, would allow for improved care and the potential for targeting novel and existing therapies to prevent SPTB, which may result in improved outcomes for both infant and mother. We have preliminary data showing that miRNA signatures in maternal blood as early as 20 weeks gestation can differentiate between those that go on to deliver at term or experience early SPTB (28-32 weeks). This project will expand on these findings to work towards development and validation of effective non-invasive biomarkers to identify women at risk for SPTB. FUNDED BY: Rotary Club of Auckland Harbourside, Inc


More Awarded Project grants
Awarded Project Grants 2019
Awarded Project Grants 2018
Project Grants Awarded 2017
Project grants awarded 2015
Project grants awarded 2014
Project grants awarded 2013