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Dr David Musson
Dept. of Medicine, The University of Auckland
Tendon damage (tendinopathy) is a severe clinical problem, costing the NZ healthcare system in excess of $280M a year, which significantly affects the quality of life of both young and aged patients, limiting movement and resulting in significant time off work. Once damaged, tendons never recover their original
structural and functional integrity; instead, disorganised scar tissue forms, diminishing both biomechanics and function. There are currently no successful therapies for treating tendinopathies, suggesting there is a clear unmet clinical need for new strategies that will improve the poor healing potential of tendons. Unfortunately, little is known regarding why tendons heal so poorly. The research carried out during this fellowship will use state of the art science to identify the mechanisms responsible for the poor healing ability of tendons, and determine whether these mechanisms can be exploited to promote a more favourable healing response. We will focus on three key areas of research, the contribution of fat derived factors to poor tendon healing, the effect damaged tendon matrix has on tendon and immune cell behaviour, and the role of excessive levels of tendon matrix proteins in disrupted tendon healing.
This Fellowship is funded through the Faculty of Medical and Health Sciences, The University of Auckland in partnership with the Auckland Medical Research Foundation.
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Dr Sarah Stewart
Dept. of Medicine, The University of Auckland
High levels of urate in the blood (hyperuricemia) can lead to the deposition of urate crystals in musculoskeletal structures and acute arthritis, known as symptomatic gout. However, many individuals with hyperuricemia remain asymptomatic; a condition present in 20% of adults. Despite the absence of symptoms, ultrasound imaging has demonstrated crystals and inflammation are still present. The pathological mechanisms involved in the transition from hyperuricemia to crystal presence, nor the long-term effects of crystal deposition in the development of gout have been investigated. This two-year project aims to explore the role of sonographically-evident crystal deposition in the transition from asymptomatic hyperuricemia to symptomatic gout as well as determine the clinical factors which predict underlying crystal deposition. An optimal ultrasound protocol and score for screening people with hyperuricemia at risk of gout will be developed which will facilitate early management strategies directed towards preventing the transition to symptomatic disease. This research has particular relevance to New Zealand, which has one of the highest global prevalence rates of gout, particularly in Māori and Pacific populations. This research has the potential to reduce the New Zealand and global prevalence of gout, improve health outcomes and reduce the healthcare economic burden associated with gout.
Funded by: David and Cassie Anderson Medical Trust
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Dr Catherine Tsai
Dept. of Molecular Medicine & Pathology, The University of Auckland
Vaccines remain the most cost-effective and feasible means of infectious disease control in the community. Well-defined synthetic vaccines based on individual peptides are specific and safe. However, peptide antigens are usually poorly immunogenic and sensitive to proteolytic degradation, thus require costly conjugation to carrier proteins and administration with potentially toxic adjuvants. Lactic acid bacteria have become promising mucosal vaccine vehicles. We have developed PilVax, a novel peptide delivery platform that utilises the group A streptococcus (GAS) pilus structure (hair-like protrusions) to carry a stabilised and highly amplified peptide on the surface of the food-grade bacterium Lactococcus lactis. The PilVax system provides the possibility to produce effective, safe and inexpensive vaccines. To demonstrate the versatility of PilVax, we initiated a pilot study to construct a vaccine against the important infectious disease tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb). Preliminary results showed that intranasal immunisation of PilVax generated strong mucosal and systemic immune responses in mice. The aim of this project is to further investigate and improve the safety and efficacy profile of TB PilVax, in order to facilitate clinical applications of this novel vaccine technology.
Dr Lisa Dawes
Dept. of Obstetrics & Gynaecology, The University of Auckland
Preterm birth, the birth of a baby before 37 weeks, is the leading cause of death in newborn babies worldwide and may impact the lifelong health of surviving babies. Despite considerable research, there is no effective way to stop preterm labour once it starts and so the focus of current practice is on prevention and optimising outcomes for babies that are born preterm. The Ruth Spencer Research Fellowship will allow completion of a series of projects which aim to improve the care provided to women who are at high risk of having their baby born early. Specialised preterm birth clinics provide a package of care for these women. We will analyse the existing international literature on preterm birth clinics and will review the treatments and outcomes from five years of practice in the only specialised preterm birth clinic in New Zealand. We will also explore the psychological wellbeing of women who are cared for in a preterm birth clinic. We expect that the new knowledge obtained from these studies will support the establishment of more preterm birth clinics throughout New Zealand to provide evidence-based care and appropriate support for all women at high risk of having a preterm birth.
Funded by: Ruth Spencer Medical Research Trust
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Dept. of Pharmacology & Clinical Pharmacology, The University of Auckland
Glioblastoma multiforme (GBM) is the most common and aggressive brain tumour in adults, and carries a dismal mean survival period of only 15 months. The presence of an immunosuppressed microenvironment is a hallmark of GBM, and this environment is in part due to the presence of dysfunctional immune cells. Microglia from the brain and tumour associated macrophages (TAMs) from the body are two cell types which are seen to have altered function within these tumours. Despite these being two different immune cell populations, due to their overlapping functions, they are often grouped as a single population. Using patient-derived tumour specimens and tumour cells, we have developed methods of identifying these populations for downstream experiments. Our goal is to investigate the respective roles of these cells in GBM and find more targeted therapies.
Funded by: The Gooduck Charitable Trust
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Dept. of Ophthalmology, The University of Auckland
Keratoconus is a potentially blinding disease of the cornea, the front window of the eye. In keratoconus, the cornea becomes thinner, weaker and protrudes which results in significant vision loss. International studies show that keratoconus may be several hundred times more common in Down Syndrome. Individuals with Down Syndrome experience a number of challenges and may be unaware of decreasing vision. Therefore, timely and appropriate treatment is delayed. In advanced keratoconus, corneal transplantation from a human donor is required. This may be avoided by a less invasive surgical procedure known as corneal collagen cross-linking, which has been shown to slow or halt the progression of disease. This treatment is more effective when it is provided in the early stages of keratoconus. Visual impairment affects many aspects of life such as learning, mobility, independence and autonomy. To reduce the burden of vision related impairment, we aim to introduce a screening and treatment initiative in New Zealand, tailored to the unique needs of this population. By preserving vision, we may preserve the unique potential and abilities of those with Down Syndrome.
Dept. of Physiology, The University of Auckland
The growth and connectivity of brain cells (neurons) is critical for normal brain development and function. Alterations to the normal development of these cells can disrupt their ability to form connections and create neural networks. Deficits in neuronal connectivity are observed in a range of neurodevelopmental disorders including autism, attention deficit hyperactivity disorder, and can induce impairments in learning and memory. However, there is limited progress in the treatment of such disorders, as the mechanisms underlying neuronal developmental and connectivity in the normal brain remain unclear. Hyaluronan is a sugar molecule expressed throughout the body and brain, which has been shown to support non-neural cell development. Evidence suggests that this sugar is expressed in the developing brain, however its specific role in brain cell development is unknown. Thus, this research will provide a novel insight into the role of hyaluronan in normal brain function, and whether disruption of hyaluronan and the extracellular matrix contributes to various neurodevelopmental disorders. Further, this study will provide information on whether targeting hyaluronan disruption is a potential therapeutic strategy to promote normal brain function.
Dr Bashar Matti
Dept. of Surgery, The University of Auckland
Prostate cancer is the most diagnosed cancer in New Zealand. It has significant attributed morbidity and mortality. Prostate Specific Antigen (PSA) is the main test currently used for prostate cancer screening. Despite being available for more than two decades, NZ data on PSA testing are scarce. Furthermore, the NZ guidelines on the utilisation of PSA for cancer screening purposes are not currently supported by validated international clinical studies. This project will investigate the patterns of PSA testing in NZ. This includes establishing an ethnicity specific, age-based reference values for PSA results. Also, it will explore the ethnic and socioeconomic disparities in cancer screening. Moreover, we will be creating a NZ specific prostate cancer risk calculator. This will be invaluable for patients (and their health providers) to better understand their risk of harbouring cancer. This project is first of a kind in Australasia and will positively impact the quality of care that NZ men receive.