Awarded Project grants

Project Grants Awarded 2017

  • 14 Dec 2017

Congratulations to the 2017 project grant recipients. To support these outstanding researchers, please consider becoming a member. Jump to the November round’s results by clicking here.
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June Round

Improving Stenting Outcome ($153,456 – 2 years) 1117003

Dr Susann Beier, Professor John Ormiston, Professor Alistair Young, Associate Professor Mark Webster, Associate Professor Brett Cowan
Dept. of Anatomy & Medical Imaging, University of Auckland

Heart disease is the most common cause of death in New Zealand. To date, 169,000 New Zealanders are diagnosed with the disease, and every 90 minutes a person dies of its consequences. This fatal damage to the blood vessels around the heart is caused over time and risk factors include a poor diet, smoking, and a family history of heart disease. Stenting treatment is common, but more than 10,000 patients experience complications and 3,000 die suddenly from stent failure. The reason why treatment fails in some patients is because the current generic method is not suitable for every individual. Differences in shape and flow of the patient’s blood vessel influence the success or failure of the treatment. We want to develop a personalised treatment, where individual differences are accounted for. We can achieve this by analysing the data of more than 600 patients. The individual differences can be explored by using a combination of sophisticated super-computer simulations, 3D-printing and radiographic imaging. This allows the testing of different treatment strategies for individuals in the lab, and can help to prevent complications and sudden death rates.

Exploiting brain mechanisms to protect from preterm brain injury? ($159,263 – 2 years) 1117009

Associate Professor Mhoyra Fraser
Dept. of Physiology, University of Auckland

Many preterm infants develop brain injury around the time of birth, with a high risk of life-long disability. Currently, we have no effective way of preventing disability. Our preliminary findings using a well-established animal model of preterm brain injury suggest for the first time that therapeutic manipulation of a critical endogenous neuroprotective anti-inflammatory mechanism can reduce damage to oligodendrocytes, the myelin-producing cells of the CNS. These findings suggest that it is possible to preserve myelination by supporting natural pathways in the brain. However, it remains to be proved whether this therapy will have a sustainable effect long-term. Thus, to replicate and extend our findings we will robustly test the long-term effects of this therapy and determine whether it improves survival of oligodendrocytes, improve myelination and reduce inflammation.

STRIDER NZAus Childhood Outcome Study ($75,061 – 2 years) 1117001

Dr Katie Groom, Professor Lesley McCowan, Professor Frank Bloomfield, Dr Christopher McKinlay
Dept. of Obstetrics & Gynaecology, University of Auckland

Being born too small poses significant risks of handicap and disease throughout a life time. There are no treatments available to improve growth before birth and so the only option is early delivery which adds further disadvantage to long term health. The drug sildenafil may be the first ever in-utero therapy for fetal growth restriction and it is currently being investigated in the STRIDER NZAus clinical trial led by researchers from the University of Auckland. Sildenafil is being given to mothers with pregnancies affected by severe fetal growth restriction across New Zealand and Australia and compared to a similar group of mothers who receive a placebo tablet. The STRIDER NZAus Childhood Outcome Study will follow the surviving babies born to mothers in this clinical trial and will assess the development of these children at the age of 2-3 years. The study will assess whether the use of sildenafil in pregnancy improves the neurological and emotional-behavioural development of these children as well as effects on their cardio-metabolic, respiratory and general health. This study will provide highly valuable information on benefit (and/or harm) as a consequence of antenatal sildenafil therapy for the treatment of fetal growth restriction.

Novel biomarker for cognitive impairments in PD ($159,294 – 2 years) 1117008

Associate Professor Jian Guan, Professor Tim Anderson, Professor John Dalrymple-alford, Dr Toni Pitcher
Dept. of Pharmacology & Clinical Pharmacology, University of Auckland

Insulin-like growth factor-1(IGF-1) is a hormone and plays a critical role in cognition. A large proportion of Parkinson disease (PD) patients develop mild cognitive impairment (MCI) in part due to poor IGF-1 function. PD with MCI has a 7-fold increased risk of developing dementia compared to those with normal cognition. Parkinson’s dementia is recognised as a primary problem affecting patient and carer well-being and a serious socio-economic issue worldwide. Earlier detection of MCI is critical for initiating effective interventions to delay the onset and slow-down progress of MCI. However there is no, yet an urgent need for, a biomarker to monitor IGF-1 function in order to identify individuals with high-risk to develop MCI and to track cognitive status. Our pilot trial suggested that the increase of plasma cyclic Glycine-Proline (cGP), a fragment of IGF-1 reflects to cognitive status prior to MCI in old people and the reduction of cGP links to PD patients with MCI. We speculate that the changes of plasma cGP may fulfil the role as the biomarker. We propose to evaluate differences in plasma cGP of PD patients with clinically defined normal cognition, MCI and dementia to assess the potential role of cGP as a marker of cognitive function in PD.

Sildenafil treatment of growth restriction and glucose metabolism ($33,538 – 18 months) 1117004

Dr Anne Jaquiery, Ms Hui Hui Phua, Ms Emma Buckels, Dr Charlotte Oyston
Liggins Institute, University of Auckland

Growth restricted babies have higher risks of perinatal complications in the short-term, and increased life-time risk of developing metabolic disease, such as type 2 diabetes. Thus, the effect of fetal growth restriction can have life-long implications for an individual beyond fetal and perinatal periods. Poor fetal growth often results from placental insufficiency, with the placenta unable to deliver adequate nutrients for fetal growth. Currently, there are no clinical treatments for pregnancies identified as having fetal growth restriction. One medication which may improve placental blood flow, thereby promoting growth by improving fetal nutrient supply, is sildenafil citrate (Viagra). In parallel with the ongoing STRIDER (NZAus) clinical trial, we have completed an experimental study in sheep using an established model of growth restriction. Sildenafil treatment of a ewe carrying a growth restricted fetal lamb improved fetal and placental growth compared to non-treated control ewes. This study will address whether Sildenafil treatment can reverse the increased risk of metabolic disease after intrauterine growth restriction, by exploring the expression of key markers of glucose metabolism in the fetal pancreas, liver, and muscle. This will add to the growing body of knowledge suggesting Sildenafil treatment could ameliorate both fetal growth restriction and the long-term effects of the in utero environment.

Understanding the CREBRF variant ($159,266 – 2 years) 1117006

Dr Troy Merry, Professor Peter Shepherd, Dr Rinki Murphy, Associate Professor Lindsay Plank
Dept. of Molecular Medicine & Pathology, University of Auckland

Obesity and type 2 diabetes (T2D) are amongst the greatest health problems currently facing New Zealand. These diseases are disproportionately greater in Māori and Pacific people than in Europeans. T2D increases the risk of developing other health conditions, including heart disease and liver diseases, and certain cancers. Obesity is the greatest risk factor for the development of T2D and is partly caused by the environment but genetic factors also play a major role. Recently it has been shown that some Samoans have a small change in their CREBRF gene, and this is associated with an increased body mass index (BMI: surrogate measure for obesity), but protects from the development of T2D. We now know that this change in the CREBRF gene is also present in 30-40% of people of Polynesian descent in New Zealand. This study will investigate why people with this change in the CREBRF gene have increased BMI but a decreased risk of T2D. Understanding how genetic variation, particularly one that is unique to people of Polynesian descent, has the potential to determine what factors contribute to obesity and T2D in our population. Such findings are likely to lead to future novel therapeutic interventions in these specific populations.

Immune priming in rheumatic fever ($160,000 – 2 years) 1117002

Dr Nicole Moreland, Professor Michael Baker, Associate Professor Pierre Smeesters
Dept. of Molecular Medicine & Pathology, University of Auckland

Rheumatic fever is a serious autoimmune disease that can develop after a Group A Streptococcus (Strep A) infection in some children. The rates of rheumatic fever in Maori and Pacific children in New Zealand are unacceptably high and drivers for disease are still poorly understood. This project will use contemporary laboratory techniques to study antibodies circulating in blood to determine the number of Strep A infections patients with rheumatic fever have experienced, compared with healthy children that live in the same area as the patients. The research will answer a fundamental question with respect to how rheumatic fever develops– do children that develop rheumatic experience more Strep A infections than those that do not? Remarkably, given the significant investment in rheumatic fever primary prevention programmes in New Zealand to treat sore throats, it is not known if the number of Strep A infections a child experiences increases their risk for developing rheumatic fever. Or alternatively, whether it is not the frequency of Strep A exposures, but an underlying susceptibility to autoimmune disease that is the driving force. Answering this critical questions will enable future prevention programs and intervention strategies to be designed and implemented with the best chance of success.

Hyaluronan in neonatal seizures ($113,745 – 2 years) 1117007

Dr Sumudu Ranasinghe, Dr Rashi Karunasinghe, Dr Justin Dean
Dept. of Physiology, University of Auckland

Seizures are the most common form of neurological emergency in newborn infants. Approximately 60% of these neonatal seizures are caused by hypoxic-ischemic encephalopathy, a lack of oxygen and blood flow to the brain, during birth. In New Zealand, approximately 1.3 in 1000 babies that are born at term experience hypoxic-ischemic encephalopathy. These neonatal seizures can increase the risk of developing further brain injury and causing life-long disabilities, including epilepsy. Although the proper management of neonatal seizures is crucial for improving the developmental outcomes for these children, there is currently no effective treatment for seizure inhibition. Indeed, the biological factors that contribute to seizure activity in neuronal cells following hypoxic-ischemic encephalopathy currently remain unclear. Our laboratory has novel evidence that an extracellular sugar called hyaluronan that surrounds neuronal cells may be important for controlling neuronal activity in the brain. We propose that hypoxia-ischemia reduces the levels of hyaluronan in the brain, and leads to increased seizure-like activity in neuronal cells. We aim to test our hypothesis using in vitro and in vivo experimental models. We will also explore whether a pharmacological inhibition of hyaluronan degradation may serve as a novel therapeutic strategy to minimise seizures after hypoxia-ischemia in the newborn.

SPACE cluster RCT in general practice ($150,012 – 2 years) 1117005

Dr Katharine Wallis, Professor Ngaire Kerse, Dr Linda Bryant, Associate Professor C. Raina Elley
Dept. of General Practice & Primary Health Care, University of Auckland

Avoidable adverse drug event hospital admissions, adverse drug events and high-risk prescribing in general practice are common, costly and distressing. High-risk prescribing is prescribing that patients at increased risk of harm. The leading risk factor for high-risk prescribing and adverse drug events is the number of medicines a person is taking. Avoidable adverse drug event admissions are increasing as more people are living longer and taking more medicines for more long-term conditions. The most effective, cost effective, and practical approach to safer prescribing in everyday practice is not yet known. We propose a trial to test the effectiveness of an intervention designed to support safe prescribing decisions in everyday practice. The intervention comprises a practice audit to identify patients with high-risk prescribing, education and patient-specific feedback to doctors, and a practice mail-out to patients identified as having high-risk prescribing encouraging them to discuss their medicines when they next see their doctor. If proven effective, cost-effective, and practical, this simple intervention could be rolled out nationally and used routinely by Primary Health Organisations to improve the safety of prescribing and minimise adverse drug event hospital admissions in older people.

November Round

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LIN28B and Wilm’s tumour ($159,999 – 18 months) 1117018

Associate Professor Alan Davidson, Dr Zhenzhen Peng
Dept. of Molecular Medicine & Pathology, University of Auckland

Wilms’ tumour is the most common form of paediatric kidney cancer, affecting 1:10,000 children, and results from inappropriate growth and persistence of embryonic renal progenitors. While advances in treatment have enhanced overall survival, recurrence of Wilms’ tumor is still a problem and there is a continuing need to understand the underlying oncogenic drivers. One such driver of Wilms’ tumorigenesis that has recently been discovered is the RNA binding protein LIN28B, which is overexpressed in ~25% of high-risk Wilms’ tumours. Understanding the effect of oncogenes such as LIN28B has been hampered by a lack of a physiologically relevant model to study cancer progression in the laboratory. Towards this goal, our group has pioneered a novel and simple protocol to generate fetal kidney tissue (organoids) from human induced pluripotent stem cells (iPSCs). In combination with CRISPR/Cas9 gene editing methods, this system provides an innovative new platform for modelling kidney diseases. Here, we propose generating kidney organoids from iPSCs that have been engineered to inducibly overexpress LIN28B with the goal of generating the first in vitro model of Wilms’ tumour. This model will provide a novel platform to better understand the molecular basis of the disease and will be useful in the future as a tool to find biomarkers (to help with risk stratification) and to test new chemotherapy treatments.

Prognostic model for breast cancer ($68,223 – 1 year) 1117011

Professor Mark Elwood, Dr Sandar Tin Tin, Associate Professor Vernon Harvey, Associate Professor Roger Marshall, Associate Professor Ian Campbell
Dept. of Epidemiology and Biostatistics, University of Auckland

This project continues our work funded by AMRF in 2016 (1 year) and will develop and assess methods to predict future outcome for women treated for breast cancer. These models 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. They will be helpful to doctors and patients in deciding on treatment options. This work is made possible by the information available in the high quality Auckland and Waikato clinical breast cancer registries, provided by over 14000 women with breast cancer diagnosed since 2000. We will develop the first New Zealand-specific model to predict breast cancer outcomes, and compare its performance with existing models that have all been developed overseas.

Arrestin mediated signalling of CB1 ($40,000 – 2 years) 1117013

Professor Michelle Glass
Dept. of Pharmacology & Clinical Pharmacology, University of Auckland

The cannabinoid receptor is a promising therapeutic target, but its widespread distribution and wide ranging effects means that adverse effects often accompany the desired effects. In the opioid field a similar problem exists, with opioid based pain relief coming with respiratory depression and constipation. Recent studies from this field have indicated that these effects can be teased apart by separating out two signalling pathways (the G-protein pathway which produces the desired response and the arrestin pathway which produces the unwanted effects). This can be achieved by designing drugs which selectively pick the G-protein pathway over the arrestin pathway, even though they are usually activated by the same receptor. In this proposal we try and understand what role the arrestins play in cannabinoid signalling and contribute to the development of selective drugs.

Lipopeptides to treat neurological disease ($158,507 – 1 year 6 months) 1117016

Dr Paul Harris, Dr Simon O’Carroll, Dr Sung Yang, Distinguished Professor Margaret Brimble
School of Biological Sciences & Dept. of Anatomy & Medical Imaging, University of Auckland

Neurological diseases affect almost one in six New Zealanders and encompasses a whole host of disorders including stroke, migraine, multiple sclerosis, spinal cord injury and epilepsy. Stroke currently ranks second after heart disease, and is the biggest cause of long-term disability in NZ. The treatment options for these diseases are very much limited and curing people is near impossible. Using medicinal chemistry and neurobiology we will create molecules that can act precisely at the site of injury or chronic disease and block the cellular signals that responsible for progression of the disease. This builds on our previous work, where we have identified a peptide (chain of amino acids) capable of blocking cellular signals that would otherwise lead to inflammation, cell death and propagation of the injury – but these molecules were not stable enough to be used as a therapy. In this research we will construct new molecules that will be long-lasting and can be used to treat conditions of the central nervous system and neurodegenerative disease.

DNA-PK inhibitors ($159,924 – 2 years) 1117020

Associate Professor Michael Hay, Professor William Wilson, Ms Rosanna Jackson, Dr Yongchuan Gu
Auckland Cancer Society Research Centre, University of Auckland

Cancer cells use DNA repair mechanisms to escape the full effects of cytotoxic chemotherapy and radiotherapy. DNA-dependent Protein Kinase (DNA-PK) plays a crucial role in repairing DNA damage caused by radiotherapy and some chemotherapy drugs. We are designing new, selective inhibitors of this enzyme and combining these with a prodrug strategy that delivers the drugs selectively to tumours. It is important to evaluate how selective these new drugs are for DNA-PK, and how well the prodrugs deliver the drugs to tumours. We will compare existing antibody-based methods with new quantitative mass spectrometry methods to detect DNA-PK inhibition in both cells and tissues. The best method will be used to determine the selectivity of a DNA-PK inhibitor and the tumour delivery of the corresponding prodrug. Validation of the methodology will provide powerful tools to advance our drug discovery efforts for DNA-PK.

SHON and endocrine therapy ($142,212 – 2 years) 5117014

Associate Professor Dong-Xu Liu, Dr Yan Li, Professor Lai-Ming Ching
School of Sciences, Auckland University of Technology

Breast cancer is the most commonly diagnosed cancer for women in New Zealand and affects one in nine women during their life time, accounting for 44% of the top 5 cancers that most often affect women. Three-quarters of all breast cancers are estrogen receptor (ER) positive. Despite the well-known high rate of drug-resistance, almost all patients with ER positive tumours are given anti-estrogen therapies as the front-line treatment for at least five years to reduce recurrence and mortality risks. One of the major reasons for this is the fact that there is no reliable means to determine who will or will not benefit from such treatments. A recent discovery shows that the presence of SHON protein in tumours markedly improves the prediction of patient response to anti-estrogen therapies. Experimental work has suggested that SHON may be an important determinant of the efficacy of anti-estrogen therapy. We propose to investigate the relationship between SHON expression and drug resistance, to accelerate the development of improved therapeutic options to effectively treat ER positive breast cancer.

Interactions between fat and tendons ($159,924 – 2 years) 1117019

Dr David Musson, Professor Jillian Cornish, Mr Brendan Coleman, Dr Dorit Naot
Dept. of Medicine, University of Auckland

There are over 4000 tendons in the body, each one a specialised tissue that connects muscle to bone and transmits tensile forces from muscle to generate movement. Tendon damage (tendinopathy) is a severe clinical problem that affects the quality of life of both young and aged persons, limiting movement and resulting in significant time off work.Recently, increased fat mass has been associated with an increased risk of tendinopathy. The traditional belief that this association was a result of increased load on the tendons, due to increased weight, has recently been reversed as upper limbs are also affected. Therefore, the mechanisms that are driving this increased risk of tendinopathy remain unknown. Fat is an endocrine organ, capable of releasing factors associated with a number of chronic diseases. These factors have not been studied in relation to tendinopathy. Therefore, this study will examine the effects of fat-derived factors on tendons through a mix of basic, pre-clinical and clinical explorations.

CaMK2 imbalance in osteoarthritis ($156,023 – 2 years) 1117012

Dr Raewyn Poulsen, Professor Nicola Dalbeth
Dept. of Medicine, University of Auckland

Approximately one in four New Zealanders over the age of 65 years have the painful, disabling condition known as osteoarthritis. Currently incurable, osteoarthritis has a significant detrimental effect on quality of life. Loss of joint cartilage is a major cause of the symptoms of osteoarthritis. This cartilage loss is due in part to abnormal behaviour of cartilage cells. It is known that excessive activity of the enzyme calcium/calmodulin kinase 2 (CaMK2) can cause this cell behaviour change. Recently, we discovered that insufficient CaMK2 activity can also cause this cell behaviour change. This suggests that rather than inhibiting CaMK2 activity (and potentially causing CaMK2 insufficiency), targeting the cause of CaMK2 hyperactivity in osteoarthritis may be a more effective means to treat disease. In this project we will establish why CaMK2 activity is increased in osteoarthritis and how the level of CaMK2 activity affects cell behaviour. We suspect that CaMK2 hyperactivity in osteoarthritis is a result of other molecules binding to CaMK2, preventing its deactivation. If we find this is the case, there are already drugs under development for the treatment of other diseases which remove these molecules from CaMK2. These drugs may also be useful for treating osteoarthritis.

Novel treatments for diabetic vascular complications ($159,582 – 2 years) 1117015

Dr Ilva Rupenthal, Professor Colin Green, Mrs Odunayo Mugisho, Dr Monica Acosta
Dept. of Ophthalmology, University of Auckland

Diabetes is amongst the greatest health problems facing New Zealand with over 240,000 people estimated to have the disease. It is associated with a number of metabolic and vascular complications that affect a variety of organs including heart, kidneys and eyes. The damage of small blood vessels and neurons at the back of the eye, termed diabetic retinopathy, can lead to vision loss affecting up to 80 percent of people who have had diabetes for over 20 years. Current treatments mainly target late stage disease signs, but are less effective in slowing disease progression. Targeting an upstream inflammatory mechanism to restore vascular integrity, allowing proper tissue nutrition and oxygenation, will be substantially more beneficial. We have identified a channel that when targeted can ameliorate the condition by not only restoring retinal blood vessels to treat the signs, but also by promoting recovery of the affected tissues preventing further vision loss. We will be testing two drugs targeting this channel in a newly developed model of diabetic retinopathy and will perform ocular assessments comparable to those performed in clinics. While this study is primarily focused on the eye, the investigated drugs may also treat other vascular problems associated with diabetes.

Automatically identifying hypoxic ischemic, high-risk preterms with Machine Learning & Artificial Neural Networks. ($159,951 – 2 years) 1117017

Associate Professor Charles Unsworth, Professor Laura Bennet, Professor Alistair Gunn
Dept. of Engineering Science, University of Auckland

This research will develop an automated risk assessment system for hypoxic ischemic (HI) preterm infants, enabling them to be prioritised effectively for new clinical trials of potential neuroprotective therapies. Currently, preterm infants get missed by current clinical criteria since their neurological signs are more subtle than at term infants. In addition, the preterm EEG record is of limited range where the evolution of HI is not always known, making it very difficult to identify where temporally the infant is in the latent phase at birth, critical to the identification of how at risk they are. This is unlike in utero sheep models of HI where the full evolution of HI is available. Using our team’s expertise in HI, ‘Machine Learning’ and ‘Artificial Neural Network Approaches’ we will derive a nonlinear map between the full evolution of HI of in utero sheep models and the limited unknown evolution of HI in preterms. Such a map will be translational, enabling us to ‘bridge the gap’ between experiment and cotside to predict where, temporally, a preterm infant is in its latent phase at birth, currently not possible. Thus, enabling the effective prioritisation of preterm infants for new randomized controlled clinical trials.

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More Awarded Project grants
Awarded Project Grants 2018
Image courtesy of Ponsulak / FreeDigitalPhotos.netProject grants awarded 2016
Project grants awarded 2015
Project grants awarded 2014
Project grants awarded 2013
Project grants awarded 2012