Fellowships Awarded 

Obesity is a growing global crisis and has been linked to significantly worse outcomes for patients diagnosed with cancer. Breast tumours grow in an environment enriched in fat (adipose) cells, which have been recently shown to interact with cancer cells and boost their growth. However, due to a lack of laboratory models that can successfully mimic the interaction between cancer cells and adipose cells in the breast, the specific role that obesity plays in this relationship remains unclear. To address this question, this study will generate human breast ‘Organoids’ from tumours donated by patients with breast cancer, which are 3D clusters of tumour cells that highly resemble the tumour from which they are derived. These Organoids, or ‘mini-tumours in a dish’, will be grown in the presence of human breast adipose cells to understand how cancer behaviour differs between obese and lean patients. This innovative model could assist in the identification of new drug targets to combat adipose-driven cancer growth, offering a specialised therapy for breast cancer patients at risk of adipose-mediated effects. The Organoids are also themselves a valuable new tool for cancer researchers in New Zealand, and could enhance the clinical translation of research discoveries in our country.

Funded by: Douglas Goodfellow Charitable Trust

Epilepsy is one of the most common and debilitating neurological conditions in the world, affecting 1-2% of the population. For 40% of women with epilepsy, their menstrual cycle will worsen their seizures; they will experience at least twice as many seizures as they ordinarily would, and the seizures may be more severe than usual. This worsening occurs at specific phases of their menstrual cycle and is called catamenial epilepsy. Catamenial epilepsy seizures frequently cannot be treated with available medicines. The exact mechanism is unknown but it is likely to involve how the brain responds to hormones and changes its sensitivity. Finding mechanisms that explain catamenial seizures and are potential targets for new treatments is essential. This fellowship is focused on finding the mechanism. We are running a study recruiting females with epilepsy who have catamenial seizures. We are comparing the findings with females who do not have seizure changes. We are testing how their brain changed over the menstrual cycle. We will also give common hormone medications to volunteer females to test changes to hormone sensitivity at different points of their menstrual cycle. For all participants we will record their brain waves (using electroencephalography) and take blood samples to test hormone levels.

Dementia is a pressing issue among the elderly, expected to double from 2015 to 2050, affecting approximately 10% of those aged 65 and over. Alzheimer's disease (AD) is a common form of dementia characterised by amyloid-beta accumulation in the brain. Despite two FDA-approved treatments targeting amyloid-beta, their limited effectiveness and severe side effects highlight the need for alternative approaches. Recent interest has focused on "inflammaging," age-related inflammation. Research has shown that the inflammasome pathway controls inflammaging and is implicated in age-related diseases like AD, making it a potential target for innovative treatment strategies for neurodegenerative diseases. For eight years, my research team has studied the inflammasome pathway in age-related neurodegenerative diseases. We found that anti-inflammasome drugs like Peptide5 and Tonabersat, protect against age-related eye and brain pathologies by reducing inflammation. However, I hypothesise that a combination of Tonabersat and Lecanemab will be the most effective approach, as Lecanemab reduces amyloid-beta levels, but cannot halt the activated inflammasome pathway during inflammaging, necessitating additional Tonabersat to reduce inflammation and halt disease progression. This research project therefore aims to assess the safety and efficacy of a combination therapy for AD treatment, utilising cell culture and mouse models.

Gestational diabetes mellitus (GDM) is a condition of high blood sugar levels first detected during pregnancy, affecting one in every eight pregnancies. In Auckland, rates have tripled over the past 15 years. GDM increases the risk of health problems in both mother and baby both during pregnancy and in the years following and contributes to health inequality over generations. I am an advanced trainee in Endocrinology with a special interest in GDM. I plan a series of studies examining how blood sugar control during a GDM pregnancy impacts outcomes 4.5 years later for both mother and child. For the mother I will investigate her sugar control, body size, diet and physical activity and overall wellbeing, and for her child I will investigate body size and behavioural and developmental outcomes using specialised questionnaires. I will also examine the effects of adherence to the recommended targets for blood sugar control, and to recommended diabetes screening follow-up after GDM, and which women are most at risk of not achieving these. This work will help to identify where interventions might be directed and guide the best use of limited health resource to improve outcomes and reduce inequalities after GDM in the future.

Funded by: Douglas Goodfellow Charitable Trust

With an increasing ageing and diabetic population, the number of New Zealanders with eye diseases requiring surgery is increasing. Two common ocular surgeries performed in NZ are cataract surgery, in which the cloudy lens is replaced by an artificial one, and vitrectomy in which the vitreous humour, a clear gel-like fluid that fills the back of the eye, is removed and replaced with a saline solution. Strong clinical evidence demonstrates that removal of the lens or vitreous accelerates the progression of secondary eye diseases, resulting in the need for further surgery within 2-5 years. With our hospital resources already stretched, the treatment of secondary eye diseases places additional strain on our hospitals. In the absence of preventative treatments, there is an urgent need to better understand the mechanisms that result in diseases following the removal of the lens or vitreous. We propose that the lens and vitreous work together to maintain the high concentrations of antioxidants in the eye that lower the oxygen levels and protect the lens and vitreous from secondary degeneration. To investigate the molecular mechanisms, this study will investigate antioxidant changes to the lens and vitreous post-surgery. The knowledge gained from this project will help us discover effective antioxidant supplementation strategies that minimise oxidative stress, restore antioxidant homeostasis, and maintain ocular health post-surgery. Such therapeutic strategies are urgently required to address the looming epidemic of diabetic and age-related eye disease.

In Aotearoa and worldwide, there are an increasing number of older patients requiring emergency laparotomy (EL). EL has high rates of morbidity and mortality, with inequitable outcomes for Māori. Older patients have increased risk of both presenting acutely with a diagnosis that may require EL and having larger impacts from a surgical procedure. Frailty and sarcopenia (an objective marker of physiologic reserve), have been identified as concepts of significance for these patients. This project will evaluate the development of a pre-operative assessment tool incorporating frailty and sarcopenia, that can be used in this setting. The study will also examine the post-operative recovery journey of the older EL patient to better understand the key patient-centred factors. This study aims to reinforce that decision making in the acute-EL setting should be tailor made, taking into consideration each individual’s physiologic status, long-term prognosis and personal goals.

Funded by: Douglas Goodfellow Charitable Trust

This project aims to understand the later life effects of antenatal corticosteroid treatment for threatened preterm birth. Corticosteroids are recommended for women at risk of preterm birth to reduce breathing problems and improve survival of their babies. However, it is not known if there are long-term health effects of this treatment. The first study in the world to assess the effectiveness of corticosteroids was done in Auckland between 1969-1974. We will study the now 50 year old children of mothers who took part in that study, and also their own children, using questionnaires, routinely collected data and clinical assessments. The findings will determine whether corticosteroid treatment has effects on later health and wellbeing, including that of the next generation, to help improve future life-long care of those born preterm.

Funded by: Ruth Spencer Charitable Trust

Ensuring the provision of equitable health services to all is a public health priority and a human right. This becomes more accentuated with minority groups who have been forcibly displaced from their home country due to persecution, conflict, and war. My fellowship will examine large data from different government agencies to identify and measure the mental well-being of refugees in New Zealand. I will develop this understanding by applying statistical models to refugees’ mental health status, service access rates, and wider settlement outcomes related to employment and education. This would help us to begin to understand what can be learnt from currently available data and what essential data is missing. This knowledge will inform future studies that would take refugees’ voices into account; an essential component to improving refugees' mental health. Results of this research will inform policy and practices to improve better settlement outcomes for this minority group. The methodological novelty holds further promise that this measure of wellbeing could be used for other minority groups, including Māori and Pacific peoples.

Obesity is a growing global crisis and has been linked to significantly worse outcomes for patients diagnosed with cancer. Breast tumours grow in an environment enriched in fat (adipose) cells, which have been recently shown to interact with cancer cells and boost their growth. However, due to a lack of laboratory models that can successfully mimic the interaction between cancer cells and adipose cells in the breast, the specific role that obesity plays in this relationship remains unclear. To address this question, this study will generate human breast ‘Organoids’ from tumours donated by patients with breast cancer, which are 3D clusters of tumour cells that highly resemble the tumour from which they are derived. These Organoids, or ‘mini-tumours in a dish’, will be grown in the presence of human breast adipose cells to understand how cancer behaviour differs between obese and lean patients. This innovative model could assist in the identification of new drug targets to combat adipose-driven cancer growth, offering a specialised therapy for breast cancer patients at risk of adipose-mediated effects. The Organoids are also themselves a valuable new tool for cancer researchers in New Zealand, and could enhance the clinical translation of research discoveries in our country.

Funded by: Douglas Goodfellow Charitable Trust

Maintaining one's balance is a complex physiological process that depends on the integration of information from many senses, particularly vision, proprioception (sensing muscle and joint movement), and input from motion sensing (vestibular) organs of the inner ear. Disorders of these vestibular organs are a common cause of imbalance, leading to reduced mobility, decreased independence, and an increased risk of falls. Falls are a major health and social concern, particularly for older people. Interestingly, there is growing evidence that our sense of hearing interacts with vestibular input from the inner ear and preliminary evidence indicates it could be used to supplement impaired vestibular function in the maintenance of balance and spatial navigation. This project aims to understand the complex interaction of hearing and vestibular function in spatial awareness and maintenance of balance. Understanding the interaction between hearing and balance could lead to novel and easily implemented hearing interventions to enhance balance rehabilitation and reduce falls risk.

Many upper gastrointestinal (GI) procedures are performed for several indications, such as for obesity or cancer. In New Zealand, the Māori population has a higher obesity prevalence of 48.3%. The most common post-surgical symptoms experienced include nausea, vomiting and indigestion. Recent technological advancements have allowed researchers to identify the presence of electrical waves in the stomach, similar to that in the heart. These electrical activities are controlled by nerve cells in the stomach wall, known as the Interstitial Cells of Cajal (ICC). Abnormalities in these electrical waves have been attributed to GI symptoms. Electrical changes following gastric surgery have yet been identified. Recently, a new technique called Body Surface Gastric Mapping (BSGM) has enabled researchers to take recordings by applying an electrode array onto the skin, similar to an ECG, without any need for surgery. This study will be the world’s first, using BSGM on patients undergoing upper GI surgery to determine the electrical changes that occur following surgery. The study will also assess ICC networks at the GI anastomosis in pig models. The results from this study will undoubtedly open a new window into GI function and have the potential to affect millions of patients worldwide undergoing GI surgery.

Funded by: Douglas Goodfellow Charitable Trust

Around 10,000 New Zealanders experience stroke each year, and most will have difficulty walking. Regaining the ability to walk independently can make the difference between returning home, or having to move to a rest home or nursing home. Patients and whānau/family would like to know whether they will walk independently again and how long this will take. Unfortunately clinicians' predictions are accurate only about half the time. The TWIST tool predicts both whether and when a patient will walk safely on their own again, with 90% accuracy. These predictions will enable patients, whānau and clinical teams to more confidently plan patients’ care, discharge, and short and long term living arrangements. In turn, this is expected to improve rehabilitation efficiency, and reduce the emotional and economic burden on patients and whānau as they adjust to life after stroke. This study will validate TWIST so it can be implemented in clinical care. It will also interview patients, whānau/family, and clinicians, to understand the perceived benefits and risks of giving and receiving prediction information. The results of this study will lay the groundwork for the next study that will see what happens when prediction information about walking is available in routine clinical practice.

In March 2022, the AMRF Covid-19 Relief Fund provided an additional $13,210. This was matched by a similar contribution from the University of Auckland’s Covid Hardship Fund.

Mortality rates for cardiovascular disease in New Zealand are decreasing, meaning people are more likely to survive events such as heart attacks and be living with heart disease. The rates of subsequent events in these people are high, and there are persistent ethnic inequities with worse outcomes for Māori and Pacific peoples. In this study of over 2000 New Zealanders who have survived their first heart attack, we aim to develop new ways to identify people at highest risk of death or rehospitalisation to enable targeting of preventative interventions. This will include exploring genetic markers of risk across New Zealand’s unique mix of ethnic groups, and several other biomarkers, in addition to the known clinical, lifestyle and environmental cardiovascular risk factors. This research may lead to novel approaches to reduce recurrent events in patients with established heart disease, identify more personalised treatments, and help increase equity of outcomes.

In March 2022, the AMRF Covid-19 Relief Fund provided an additional $11,825. This was matched by a similar contribution from the University of Auckland’s Covid Hardship Fund.

Funded by: Douglas Goodfellow Charitable Trust

The increasing availability of large international genetic databases and inexpensive, cloud-based computation makes now an ideal time to develop a tool which can show a comprehensive picture of mutations in the context of regulatory elements, specifically 3-D genome structure. The bioinformatics approach will be fast (minutes), inexpensive to operate (only data storage costs), provide open access to mutation annotation for all clinical and genomics experts, and attribute impact to the numerous cancer variants currently classified as having “unknown significance”. The value of this approach is to improve future diagnostics with the power to understand non-coding mutations, to alleviate: 1. patient anxiety (“Is my family member hurt by these variants of unknown significance?”); 2. clinician overburden (overwhelming information without clear clinical answers); and 3. diagnostic cost (expensive expertise to diagnose individuals with unknown burden). Therefore, this project could lead to a beneficial way to screen mutations and reduce the burden of having so many unknowns.

In March 2022, the AMRF Covid-19 Relief Fund provided an additional $13,763. This was matched by a similar contribution from the University of Auckland’s Covid Hardship Fund.

Funded by: Douglas Goodfellow Charitable Trust

Diagnosing different skin diseases is dependent on an instrument’s ability to identify the unique signals of each disease. Unstudied skin diseases have ill-defined biochemistry and require analytical techniques that can provide a broad biomolecular survey. Two techniques are capable of this, and they generate two different spectral fingerprints. Raman spectroscopy is non-invasive (making it ideal for diagnostics) and provides a precise ratio of biomolecular components present in tissue (e.g. lipids, proteins, etc). Mass spectrometry (MS) is invasive but identifies all individual biomolecules present by their mass-to-charge (m/z) ratio. By developing computational algorithms, the precise molecular information from mass spectrometry can be incorporated into Raman measurements with which the unique aspects of any skin disease can be more precisely identified. Discoid lupus erythematosus (DLE) is a case study for these techniques due to its distinctiveness compared to other types of lupus. Unless one is an expert dermatologist, its classification and diagnosis are challenging. This project will contribute to a fundamental understanding of how DLE differs from other skin diseases. Furthermore, the computational methods that provide enhanced dermatological diagnostic resolution will be incorporated into the development of a Raman spectroscopy-based portable device (currently under development).

Funded by: Edith C Coan Trust