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Major funding for innovative Otago health research

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Monday, 9 June 2014 2:22pm

Dr Richard Blaikie
Professor Richard Blaikie
Deputy Vice-Chancellor (Research & Enterprise)

More than $31.3M in new health research funding has been awarded to Otago researchers to support a range of world-class studies aimed at improving New Zealanders’ health and well-being.

The latest Health Research Council of New Zealand annual funding round results were announced today. Otago researchers gained 24 contracts, including three major multi-million, five-year programmes, 14 projects and seven grants for emerging researchers. Otago’s successful applicants span the University’s campuses in Dunedin, Christchurch and Wellington and together gained the largest share of funding of any institution in this latest round.

One of the major programmes, led by Anatomy Professor David Grattan, will examine how the hormonal changes responsible for helping women’s brains adapt to pregnancy operate – and the serious complications that can occur for both mother and baby when these changes go awry.

Resulting conditions can include maternal obesity, gestational diabetes, pre-term labour and postnatal depression. Such adverse events can also have serious consequences on the baby, changing brain development and increasing life-long risk of many diseases, including obesity and mental illness.

Another programme, headed by Biochemistry Associate Professor Tony Merriman, aims to improve the understanding of the causes, treatment and prevention of gout by studying the complex interplay of genetic and environmental risk factors, such as alcohol and sugary drinks, in the development of this painful and debilitating disease. The researchers will also examine whether genetic makeup influences response to the standard gout drug, allopurinol.

The third programme extends the world-leading heart hormone discoveries by researchers at the University’s Christchurch Heart Institute. This research team, led by Professor Mark Richards, will evaluate markers for unmet needs in diagnosing and managing heart failure.

The team’s objectives include early detection of dangerous complications of heart failure—kidney injury and pneumonia—and fine-tuning of the use of markers to guide diagnosis and management of the overall condition.

The three programmes are funded at around $5M each over five years.

Deputy Vice-Chancellor (Research and Enterprise) Professor Richard Blaikie says he is delighted by the success of all the Otago recipients in this highly contested annual funding round.

“The breadth and depth of skills that are needed to contribute to high-quality health-related research is highlighted in these results. The lead researchers represent more than ten disciplines across three of Otago’s academic divisions, including—but not limited to—anatomy, biochemistry, general practice, human nutrition, marketing, medicine, pathology, pharmacy, psychology, public health, and women’s and children’s health. Many of the collaborative teams also have strong researchers trained in humanities and social science disciplines,” Professor Blaikie says.

It is also very pleasing to see that half of the 14 Emerging Researcher First Grants went to applicants from Otago, he adds.

“This shows that not only are the University’s well-established staff continuing to put forward excellent research proposals, their colleagues at an early-career stage are also becoming the research leaders of tomorrow,” he says.

One of the seven Emerging Researcher Grants goes towards a study examining whether eating bread made with either less salt or with increased levels of L-arginine from hazel nuts or nitrate from beetroot may be a simple and effective way to reduce high blood pressure.

Another grant involves developing a novel way to selectively target cancer cells for chemotherapy so that tumour-killing drugs are only released when such cells are identified, sparing healthy cells. Also among these grants is one that will focus on discovering why Maori suffer worse disability outcomes after injury.

The 14 Otago Project Grants range from basic biomedical investigations into the genetic regulation of brain stem cell development to devising interventions to improve health outcomes for patients suffering multiple diseases.

They focus on topics that include assessing an existing antidepressant as a pain treatment for knee osteoarthritis, and working towards a new therapy to raise levels of HDL (‘good’ cholesterol) to reduce cardiovascular disease risk.

Other projects involve investigating the potential role of a tumour-suppressor gene variant in autoimmune diseases such as arthritis, and teasing out how the sex hormone AMH regulates female reproduction. Another will explore a new biological marker’s potential for diagnosing specific causes of anxiety disorders.

One Christchurch campus project aims to improve the diagnosis and treatment of Legionnaires’ disease in New Zealand, while another will use gene testing and brain imaging to attempt to find a way to predict the onset of cognitive decline in patients with Parkinson’s.

Among the public health-related projects are an evaluation of the effectiveness of New Zealand’s alcohol reform legislation and a comprehensive analysis by Wellington campus researchers of survey data to improve understanding of the impact of racial discrimination on adult health and wellbeing.

For more information, contact:

Professor Richard Blaikie
Deputy Vice-Chancellor (Research & Enterprise)
University of Otago
Tel 64 3 479 8513
Email dvc.research@otago.ac.nz

Otago’s HRC annual round funding recipients:

(Please note: Only the first named investigator is listed)

Programmes:

Professor David Grattan (Anatomy)
Healthy pregnancy, healthy babies
60 months, $4,987,293
Telephone: (03) 479 7442

Associate Professor Tony Merriman (Biochemistry)
Urate and gout: genetic control, environmental and drug interactions
60 months, $4,999,512
Telephone: (03) 479 5798

Professor Mark Richards (Medicine, Christchurch)
Heart Failure: markers and management
60 months, $4,980,858
Telephone: (03) 364 1117

Projects:

Professor Tim Anderson (Medicine, Christchurch)
Genetics, brain imaging, and cognitive decline in Parkinson’s disease
36 months, $1,178,803
Telephone: (03) 378 6079

Professor Antony Braithwaite (Pathology, Dunedin)
A role for p53 isoforms in inflammatory disease
36 months, $1,176,905
Telephone: (03) 479 7165

Professor Susan Dovey (General Practice & Rural Health)
Patient harms in New Zealand general practices: Records review study
36 months, $1,174,690
Telephone: (03) 479 4135

Dr Ricci Harris (Public Health, Wellington)
Understanding the impact of racial discrimination on adult health and wellbeing
36 months, $452,777
Telephone: (04) 385 5418

Dr Ben Hudson (General Practice, Christchurch)
A randomised controlled trial of Nortriptyline in knee osteoarthritis
36 months, $1,190,921
Telephone: (03) 364 3607

Associate Professor Greg Jones (Surgical Sciences)
An epigenome-wide study for abdominal aortic aneurysm
36 months, $1,138,354
Telephone: (03) 474 0999

Associate Professor Bev Lawton (Primary Health Care & General Practice, Wellington)
Addressing avoidable harm suffered by Māori babies
36 months, $1,199,999
Telephone: (04) 806 1893

Dr Brett Maclennan (Preventive & Social Medicine)
Evaluation of New Zealand's alcohol reform legislation
48 months, $1,190,521
Telephone: (03) 479 4080

Associate Professor Sally McCormick (Biochemistry)
Restoring HDL levels
36 months, $1,044,053
Telephone: (03) 479 7840

Professor Ian McLennan (Anatomy)
AMH regulation of female reproduction
48 months, $1,169,770
Telephone: (03) 479 7346

Professor Neil McNaughton (Psychology)
Clinical translation of an anxiety process biomarker
36 months, $1,040,728
Telephone: (03) 479 7634

Professor David Murdoch (Pathology, Christchurch)
Legionnaires’ disease in New Zealand: improving diagnostics and treatment
30 months, $999,467
Telephone: (03) 364 1530

Professor Stephen Robertson (Women’s & Child Health)
Defining genetic regulators of neurogenesis in humans
36 months, $1,185,630
Telephone: (03) 479 7469

Associate Professor Diana Sarfati (Public Health, Wellington)
Multimorbidity: the most common chronic condition of all
36 months, $1,199,968
Telephone: (04) 385 5999

Emerging Researcher First Grants

Dr Katherine Black (Human Nutrition)
Which diet? Dietary interventions and blood pressure
24 months, $149,994
Telephone: (03) 479 8358

Dr Allan Gamble (Pharmacy)
Bioorthogonal Prodrug Activation for Targeted Chemotherapy
36 months, $144,275
Telephone: (03) 479 7324

Dr Christopher Jackson (Medicine, Dunedin)
Primary rectal cancer management in advanced disease with chemotherapy
36 months, $145,529
Telephone: (03) 474 0999 Ext 8760

Dr Sandra Mandic (Physical Education, Sport and Exercise Sciences)
Built Environment and Active Transport to School: BEATS Parental Survey
36 months, $149,941
Telephone: (03) 479 5415

Dr Ninya Maubach (Marketing)
Heuristics in the supermarket: Do food labels support healthy choices?
36 months, $109,940
Telephone: (04) 918 6686

Dr Tracy Melzer (Medicine, Christchurch)
Imaging markers of imminent cognitive decline in Parkinson’s disease
36 months, $149,943
Telephone: (03) 378 6075

Dr Emma Wyeth (Preventive & Social Medicine)
Maori Disability Outcomes: Pathways and experiences after injury
36 months, $149,410
Telephone: (03) 479 4064

Programme Grants

Healthy pregnancy, healthy babies

Professor David Grattan (Anatomy)
Other Otago Named Investigators:
Associate Professor Colin Brown (Physiology)
Dr Christine Jasoni (Anatomy)

The most important time determining life-long health status of an individual is that spent developing in utero during pregnancy. To provide the optimal environment for development of her baby, the mother’s body undergoes numerous changes. Apart from obvious adaptations in the uterus and breast, there are other equally-important changes, particularly in the brain; appetite increases, hormone secretion is altered, and moods and behaviour change. These adaptations are driven by pregnancy hormones, and in particular, prolactin and placental lactogen (PL). If these changes do not occur properly, complications may occur, including gestational diabetes, preterm labour, and postpartum depression. Such adverse events can also have serious consequences on the baby, changing brain development and increasing life-long risk of many diseases, including obesity and mental illness. This programme will evaluate how prolactin/PL helps the maternal brain adapt to pregnancy, and the consequences for the mother and baby when adaptive responses are compromised.

Objective Leaders

Objective or Project Title
Leading Named Investigator
Regulation of body weight and glucose homeostasis during pregnancyGrattan, DR
Role of prolactin in the activation of oxytocin neurons at birthBrown, CH
How challenges in the womb can increase life-long disease riskJasoni, CL
Feasibility study to evaluate if biomedical observations translate into clinical samplesGrattan, DR McCowan, L – University of Auckland

Urate and gout: genetic control, environmental and drug interactions

PI: Associate Professor Tony Merriman (Biochemistry)
Other Otago Named Investigators:
Prof Lisa Stamp, (Medicine, Christchurch)
Associate Professor Greg Jones (Surgical Sciences)
Dr Rebecca Roberts (Surgical Sciences)
Dr Philip Wilcox (Biochemistry)
Mr Daniel Wright (Pharmacy)

Gout results from increased blood levels of the chemical urate that precipitates in the joints and causes painful gout attacks. Gout is of particular relevance to Aotearoa New Zealand due to the high prevalence and severe disease in Māori and Pacific people. Gout is also associated with diabetes, chronic kidney disease and heart disease. Genetic inheritance is important in determining levels of urate and gout, and is known to interact with environmental risk factors such as alcohol, sugary drinks, and diuretics. Our goal is to precisely understand the genes that are important and how they work with diet and diuretics to influence urate levels and gout. We will also investigate whether genetic makeup influences how people respond to the gout drug allopurinol. We anticipate this research will contribute substantially to gout treatment guidelines and increase scientific and medical knowledge and public awareness of the causes, treatment and prevention of gout.

Objective Leaders

Objective or Project Title
Leading Named Investigator
Genome-wide association study in clinically-ascertained goutMerriman, T
Urate; genetic and environment control in population studiesMerriman, T
Gene-environment interactions in serum urate: intervention studiesDalbeth, N – U Auckland
Genetics of response to allopurinolStamp, L

Heart Failure: markers and management

Professor Mark Richards, (Medicine, Christchurch)
Other Otago Named Investigators:
Prof Vicky Cameron (Medicine, Christchurch)
Associate Professor Richard Troughton (Medicine, Christchurch)
Associate Professor Chris Pemberton (Medicine, Christchurch)
Associate Professor Miriam Rademaker (Medicine, Christchurch)
Associate Professor Chris Frampton, (Medicine, Christchurch)
Prof Chris Charles (Medicine, Christchurch)
Dr Leigh Ellmers (Medicine, Christchurch)
Associate Professor John Pickering (Medicine, Christchurch)
Dr Anna Pilbrow (Medicine, Christchurch)

Heart Failure (HF) will affect 20% of people now aged 40 years and confers high rates of early readmission and death. Our integrated programme addressing unmet needs in HF includes: (1) The IMPERATIVE-HF controlled trial of intensified immediate post-discharge management using special blood tests to individually grade risk and guide intervention with rapid adjustments to treatment to improve outcomes. (2) Testing of candidate kidney damage markers for early warning of this frequent and dangerous complication of HF. (3) Establishing correct sampling times for novel markers for best prediction of early and long term outcomes in HF. (4) Testing our newly discovered markers for early warning of pneumonia complicating HF. (5) Clarification of diagnoses and testing management plans for patients in the Emergency Department with breathlessness or chest pain who do not have clear-cut HF or heart attacks but who nevertheless have elevated blood biomarkers and a poor outlook.

Objective Leaders

Objective or Project Title
Leading Named Investigator
A: IMPERATIVE-HFTroughton, R
B1: IDENTAKIT-HFEndre, Z – University of New South Wales
B2: Mechanisms and markers of Acute Kidney Injury and repair in ADHFRademaker, M
C: TEMPORAL-HFRichards, M
D: SIGNIFICANT-HFPemberton , C
E: IMPPAACTThan, M – Canterbury District Health Board

Project Grants:

Genetics, brain imaging, and cognitive decline in Parkinson's disease

Professor Tim Anderson (Medicine, Christchurch)
Other Otago Named Investigators:
Prof Martin Kennedy (Pathology, Christchurch)
Dr Tracy Melzer (Medicine, Christchurch)
Dr John Pearson (Population Health, Christchurch)

Many people with Parkinson’s are at risk of dementia but we have been unable to predict when that will occur. We will do advanced brain scans (MRI and PET) gene testing and clinical evaluations in 85 Parkinson’s patients who have mild cognitive impairments, who we know are at higher risk, and then determine whether they progress to dementia over the subsequent three years. By identifying characteristics present in the scans and genetic tests of those who develop dementia, compared to those who do not, we can advance our understanding of this important issue and establish a useful and reliable tool for researchers and clinicians. It is critical that we can do this so that preventative treatments to protect against dementia can be targeted at the most appropriate patients when that treatment becomes available and also to select the right “at risk” Parkinson’s patients for trials of new treatments.

A role for p53 isoforms in inflammatory disease

Professor Antony Braithwaite (Pathology)
Other Otago Named Investigators:
Professor Margaret Baird (Pathology)
Professor Lisa Stamp, (Medicine, Christchurch)
Dr Paul Hessian (Medicine, Dunedin)

We investigate a role for oncoprotein p53 variants, especially D133p53, in the development of autoimmune disease. The work is based on our transgenic mouse expressing an analogue of D133p53 (designated D122p53), which develops features of autoimmune disease by modulation of pro-inflammatory genes. We will characterize inflammatory pathologies of the mice and investigate a role for the cytokine IL-6 and the STAT-1/interferon pathway as ‘driving’ autoimmune disease, using D122p53 mice that lack the IL-6 or STAT-1 genes. To translate these findings to man, we will analyse Rheumatoid Arthritis joint tissue for D133p53 expression, relate that to pathology and inflammatory gene transcripts and quantitate the levels of other p53 isoforms and novel variants to determine if they are associated with inflammatory disease. We will interrogate publically available RA transcript databases for similar associations using bioinformatics. The outcome of our experiments will be to define the role p53 isoforms play in autoimmune disease.

Patient harms in New Zealand general practices: Records review study

Professor Susan Dovey (General Practice & Rural Health)
Other Otago Named Investigators:
Dr Katharine Wallis (General Practice & Rural Health)
Dr Wayne Cunningham (General Practice & Rural Health)
Dr Martyn Williamson, (General Practice & Rural Health)
Associate Professor David Reith (Women’s & Children’s Health)
Dr Ari Samaranayaka (Preventive & Social Medicine)
Professor Murray Tilyard (General Practice & Rural Health)

This study aims to use information in general practice records to describe the types, frequency, preventability and severity of harms patients experience due to their healthcare. General practitioners will review three years of records (consultation notes, prescriptions, investigations, referrals, and summaries of hospital care) from 9000 patients registered in 60 general practices. The types of patient harms recorded, their preventability and outcomes will be documented. Both general practices and patients will be randomly selected so that the study’s results will apply nationally, after weighting. Equal numbers of small, medium-sized, large, urban and rural general practices will participate in the study because there may be systematic differences in patient harms in these different types of practices. The study’s results will be used in the development of an audit tool to help general practices monitor and improve safety and provide information to help patients, doctors, and planners make safer healthcare decisions.

Understanding the impact of racial discrimination on adult health and wellbeing

Dr Ricci Harris (Public Health, Wellington)
Other Otago Named Investigators:
Dr Donna Cormack (Public Health, Wellington)
Dr James Stanley (Dean’s Department, Wellington)
Ms Ruruhira Rameka (Public Health, Wellington)

Racism is an important social determinant of health that underpins ethnic and racial health disparities. This study seeks to provide a comprehensive understanding of the impacts of racism on adult health and wellbeing, and ethnic inequalities in New Zealand. Specifically we aim to look at experience of racial discrimination for different ethnic groups (Māori, Pacific, Asian, European), if any changes have occurred over time, whether experience of racism is linked to poorer health and wellbeing measures including healthcare, and how different forms of discrimination combine with racism to affect peoples’ health and wellbeing. This will be undertaken through a comprehensive analysis of secondary data from multiple national surveys including the New Zealand Health Survey (2002/03, 2006/07, 2011/12) and the General Social Survey (2008, 2010, 2012). Study findings will inform anti-racism and public health interventions in on-going efforts and actions to improve health and eliminate ethnic health inequalities.

A randomised controlled trial of nortriptyline in knee osteoarthritis

Dr Ben Hudson, General Practice UOC
Other Otago Named Investigators:
Professor Les Toop (General Practice, Christchurch)
Professor Lisa Stamp, (Medicine, Christchurch)
Dr Jonathan Williman (Population Health, Christchurch)
Professor Gary Hooper (Orthopaedic Surgery & Musculoskeletal Medicine, Christchurch)
Associate Professor Dee Mangin (General Practice, Christchurch)
Ms Bronwyn Thompson (Orthopaedic Surgery & Musculoskeletal Medicine, Christchurch)

Osteoarthritis (OA) is a very common and painful condition. Medicines currently available for treating OA pain are not ideal: they are either inadequately effective or cause unpleasant or dangerous side effects. Recent research has shown how the brain processes pain in OA and this has opened up the possibility of using different types of medicines for OA pain. Nortriptyline (an antidepressant) has been used to treat persistent pain in other conditions, and other antidepressants may reduce pain in knee OA. It is not known whether nortriptyline is useful in this condition. We plan to test this effect by randomly allocating participants to treatment with nortriptyline or placebo and to measure changes in their pain before and after a period on the medication. We hope that this will tell us whether nortriptyline will be helpful. If it is, then we believe that many people may benefit from taking this medicine.

An epigenome-wide study for abdominal aortic aneurysm

Associate Professor Greg Jones (Surgical Sciences)
Other Otago Named Investigators:
Professor Andre Van Rij (Surgical Sciences)
Professor Ian Morison (Pathology)

Abdominal aortic aneurysm (AAA) is a common disorder found in ~5% of all New Zealand men over the age of 60. Over 500 surgical repairs are conducted in New Zealand at a cost of over $10M per annum. It is well known that both inherited (genetic) and environmental factors, such as smoking, contribute to an individual’s risk of developing an aneurysm. The objective of this study is to better understand the ways in which genetic and environmental factors interact (epigenetics). To do this we will examine a large number of DNA modifications (epigenetic markers) in blood cells and compare expression in those with and without AAA. We will also compare epigenetic markers with genetic and demographic risk factors from the same study participants. In so doing we hope to identify (1) novel risk prediction markers and (2) possible therapeutic drug targets to help treat this life threatening disease.

Addressing avoidable harm suffered by Māori babies

Associate Professor Bev Lawton (Primary Health Care & General Practice, Wellington)
Other Otago Named Investigators:
Ms Charrissa Makowharemahihi (Primary Health Care & General Practice, Wellington)
Dr Jane Macdonald (Primary Health Care & General Practice, Wellington)
Dr Sara Filoche (Primary Health Care & General Practice, Wellington)
Dr James Stanley (Dean’s Department, Wellington)
Dr Peter Abels (Obstetrics & Gynaecology, Wellington)
Ms Bridget Robson (Public Health, Wellington)
Dr Maggie Meeks (Paediatrics, Wellington)
Ms Selina Brown (Primary Health Care & General Practice, Wellington)

The babies of Māori women experience nearly twice the burden of potentially preventable death, than the babies of New Zealand European (NZE) mothers. Severe acute maternal harm or morbidity (SAMM) is strongly associated with maternal death, stillbirth, neonatal death and harm. Our research into SAMM (mothers) has shown a high stillbirth rate (7%) and 24% of live babies had oxygen deprivation, potentially leading to brain damage. To examine these harms, this new proposal SAMM Kids will study the causes, consequences and preventability of poor baby outcomes for women who have had a SAMM event, analysing disparities between Māori and NZE, using expert case review and interviewing whānau, in order to reduce the impact of this harm for the Māori infant and whānau. The results of SAMM Kids will lead to clinical and educational interventions to reduce preventable Māori fetal/infant harm and mortality and reduce the on-going impact on their whānau.

Evaluation of New Zealand’s alcohol reform legislation

Dr Brett Maclennan (Preventive & Social Medicine)
Other Otago Named Investigators:
Prof Kypros Kypri (Preventive & Social Medicine)
Prof Jennie Connor (Preventive & Social Medicine)
Mr Tuari Potiki (Office of Maori Development)

Alcohol consumption accounts for 5.4% of deaths and 6.5% of disability-adjusted life years lost annually in New Zealand. The Sale and Supply of Alcohol Act (2012), introduced to reduce alcohol-related harm, comes into full effect in 2014. The Act eschews many effective, centralised strategies (e.g., increasing tax on alcohol), instead aiming to give communities more say on where and when alcohol is sold in their area, via the option of developing Local Alcohol Policies. The proposed research will use surveys, key informant interviews and administrative data to evaluate community uptake of the new opportunities provided by the legislation and the impact they have on alcohol availability, hazardous drinking and related harm. The results will evaluate whether the new law meets its explicit public health objectives and will contribute to the evidence base underpinning the development of policy aimed at reducing alcohol-related injury and disease in New Zealand and other countries.

Restoring HDL levels

Associate Professor Sally McCormick (Biochemistry)
Other Otago Named Investigators:
Professor Michael Williams (Medicine)
Associate Professor Greg Jones (Surgical Sciences)
Associate Prof Tony Merriman (Biochemistry)

Low levels of high density lipoprotein (HDL) are a major risk factor for developing cardiovascular disease (CVD). We have uncovered defective trafficking of the ABCA1 cholesterol transporter as a major cause of low HDL. Furthermore, we have shown that ABCA1 trafficking can be restored with the chemical chaperone, 4-phenylbutyrate (4-PBA), although the mechanism is unknown. We aim to identify the molecules involved in the restoration of ABCA1 trafficking by 4-PBA and to identify new molecules and genes that regulate HDL production. We will use cell biology and proteomic approaches as well as new DNA sequencing technology to achieve this. Outcomes include a potential new “HDL increasing therapy” which could lead to clinical trials as well as the identification of new targets for manipulating HDL levels. Our research could lead to better management of lipid risk factors and a reduction in CVD risk for many people.

AMH regulation of female reproduction

Professor Ian McLennan (Anatomy)
Other Otago Named Investigator:
Dr Michael Pankhurst (Anatomy)

This project will define the basic endocrinology of anti-Müllerian hormone (AMH), to understand its function and to rapidly improve its clinical utility as a biomarker of ovarian function. We have discovered that the ovary releases two forms of AMH; an inactive precursor (proAMH) and a receptor-binding form (AMHN,C). proAMH may be a long-term basal regulator whereas AMHN,C may be an acute regulator that varies depending on the state of the ovary. We have invented AMH species-specific ELISAs, and we determine whether form of AMH varies during menstrual cycling and pregnancy. We will also determine whether proAMH in blood is converted to AMHN,C, using mice. The AMH released by the ovary may control miscarriage during pregnancy. We will test this hypothesis by comparing and contrasting pregnancies in mice with altered AMH expression. The project outcomes may improve the assessment of subfertility in women and yield therapeutic developments related to recurrent miscarriage.

Clinical translation of an anxiety process biomarker

Professor Neil McNaughton (Psychology)
Other Otago Named Investigator:
Professor Paul Glue (Psychological Medicine)

“Anxiety disorders” are the commonest mental disorders in New Zealand; but their diagnosis is still based on clinical symptom check lists with no biological markers to diagnose specific causes. Over recent decades, we have developed: 1) a detailed theory of the brain systems controlling threat-avoidance and threat-approach – where, in specific brain structures, activity generates specific normal behaviours, hyperactivity generates abnormal behaviours, and hyper-reactivity (hypersensitivity to input) generates specific clinical syndromes; and, 2) a specific non-invasive measure of activation of the threat-approach system in humans. We will test if our new biological marker divides untreated “anxiety” patients with superficially similar clusters of symptoms into distinct high scoring and low scoring groups with different treatment-responses. If positive, the results will validate the first human biological marker for a theoretically-defined “anxiety” syndrome. This marker should predict treatment efficacy better than current symptom-based diagnoses; greatly improving treatment outcomes and cost-effectiveness.

Legionnaires' disease in New Zealand: improving diagnostics and treatment

Professor David Murdoch (Pathology, Christchurch)
Other Otago Named Investigators:
Associate Professor Patricia Priest (Preventive & Social Medicine)
Professor Stephen Chambers (Pathology, Christchurch)
Dr Ian Sheerin (Population Health, Christchurch)

Legionnaires’ disease is a severe type of pneumonia that is under-diagnosed in New Zealand. Special tests are required to make a diagnosis of Legionnaires’ disease, but there are no clear guidelines about which patients to test. An enhanced testing system for Legionnaires’ disease was developed in Canterbury and has been used there since 2010. The system involves targeted use of the current best test for Legionnaires’ disease: PCR (polymerase chain reaction), which detects bacterial DNA. This approach has uncovered many cases of Legionnaires’ disease that would have otherwise gone undetected. This study will roll out this same testing strategy across New Zealand for one year in order to measure the national burden of Legionnaires’ disease, to improve patient treatment, to identify cost-effective ways to test for Legionnaires’ disease in the future, and to create better guidelines for the treatment of pneumonia.

Defining genetic regulators of neurogenesis in humans

Professor Stephen Robertson (Women’s & Children’s Health)
Other Otago Named Investigator:
Dr David Markie (Pathology)

This proposal will advance understanding of genetic regulators of neural stem cells in the brain through the study of a set of defined disorders characterised by brain malformations. These disorders have a signature indicating that neural stem cell function is defective, resulting in the distortion of the orderly layered structure of this organ. We hypothesise that the study of these conditions will point us to key genes and signaling pathways that regulate brain development by controlling how stem cells behave. The health impact of this knowledge lies in that all infants are born with substantial reserves of neural stem cells. They hold the potential to repair or replace damaged or dead neurons in children who have sustained brain insults. Fleshing out a genetic map of regulators of neural stem cells will facilitate the ability to mobilise this endogenous reserve of cells therapeutically in the context of neurological disease in young children.

Multimorbidity: the most common chronic condition of all

Associate Professor Diana Sarfati (Public Health, Wellington)
Other Otago Named Investigators:
Dr James Stanley (Dean’s Department, Wellington)
Associate Professor Dee Mangin (General Practice, Christchurch)
Professor Tony Dowell (Primary Health Care & General Practice, Wellington)
Dr Jason Gurney (Public Health, Wellington)
Associate Professor Louise Signal (Public Health, Wellington)

Multimorbidity is the coexistence of more than one chronic disease. Multimorbidity results in high health service use, competing demands on patients and health care professionals, reduced quality of life and higher mortality, with greater impact for Māori and Pacific people, and those living in deprived areas. Research focused on multimorbidity is scarce internationally and almost non-existent in NZ. The aims of the research project are to 1) describe the prevalence, patterns and impact of multimorbidity in NZ using routinely collected data; 2) understand and describe patients’ understanding of, and experience of living with multimorbidity, using focus groups, in-depth interviews and a survey of patients with multimorbidity; and 3) develop interventions aimed at reducing the impact of multimorbidity in NZ including identifying best clinical practice models, focused amendment of clinical guidelines and identification of pro-equity interventions. Our aim is to improve health outcomes for patients with multimorbidity.

Emerging Researcher First Grants recipients

Which Diet? Dietary interventions and blood pressure

Dr Katherine Black (Human Nutrition)
Other Otago Named Investigators:
Dr Rachel Brown (Human Nutrition)
Dr Alexander Chisholm (Human Nutrition)
Mr Andrew Gray (Preventive & Social Medicine)

Hypertension (high blood pressure) is a key contributor to cardiovascular disease and stroke, two leading causes of death in New Zealand. Lifestyle interventions aimed at attenuating hypertension and cardiovascular disease often have poor long term adherence due to the sheer amount of changes required. This study will examine the impact of changing one significant aspect of diet - the composition of bread - on blood pressure and resulting cardiovascular health. We will investigate three nutritional components that have been shown to influence blood pressure: sodium (salt), nitrate (beetroot) and L-arginine (hazelnuts). This randomised parallel intervention study will have four arms: low sodium bread, beetroot bread, nut bread and a control bread. Participants will be high bread consumers with elevated risk of cardiovascular disease, and at least one metabolic syndrome risk factor. We anticipate that one simple dietary change – an alternate bread recipe – could lower blood pressure and improve cardiovascular health.

Bioorthogonal Prodrug Activation for Targeted Chemotherapy

Dr Allan Gamble (Pharmacy)

Drugs currently used to treat cancer are non-selective, killing healthy as well as tumour cells. In this project known anti-cancer drugs will be masked into an inactive (prodrug) form. Unlike other prodrugs which slowly release active drug distant from the tumour, our approach will enable control over when, where and how much active drug is released by using a ‘two-drug’ activation strategy. Firstly, the activating molecule, which is targeted to a tumour-specific receptor, will be administered. The prodrug will then be given, and only when it encounters the tumour-bound activator will the tumour-killing drug be released. This represents a new technology in tumour-targeted drug delivery by using a bioorthogonal chemical reaction that occurs only between the prodrug and its activator, providing complete tumour-selectivity. The pre-clinical data from this project will be used to evaluate the potential of this technology in the clinic.

Primary Rectal Cancer Management in Advanced disease with Chemotherapy

Dr Christopher Jackson (Medicine)
Other Otago Named Investigators:
Professor Parry Guilford (Biochemistry)
Professor John McCall (Surgical Sciences)
Associate Professor Mark Thompson-Fawcett (Surgical Sciences)

New Zealand has one of the highest rates of rectal cancer in the world, and ¼ people with rectal cancer have secondary spread of cancer at the time of diagnosis. We propose a single arm phase 2 study with blood and tumour biopsy collection to test the effectiveness of a “chemo first” approach to this group of patients. Circulating tumour DNA (ctDNA) will be collected and assessed as: a surrogate for biopsy of the primary and metastases; tumour response to therapy; to detect developing mutations that might predict resistance to chemotherapy. Multiple biopsies will be collected over time to identify changes in tumour gene expression that will help understand molecular evolution of rectal cancer, and to identify (and later target) the emerging “lethal clone”.

Built Environment and Active Transport to School: BEATS Parental Survey

Dr Sandra Mandic (School of Physical Education, Sport and Exercise Sciences)
Other Otago Named Investigators:
Dr Antoni Moore (Surveying)
Dr John Williams (Marketing)

The lack of physical activity in adolescents is a global health problem. Active transport to school is a convenient way to increase physical activity in the adolescent’s day-to-day schedule and adopt an environmentally sustainable travel practice. The purpose of the BEATS Parental Survey is to examine parental perceptions of different transport modes to school, motivations and barriers for active transport to school, perceptions of the built environment and safety of the route to school, physical activity habits, weight status, health behaviours and route to work and their relationship to active transport to school habits in adolescents. This cross-sectional study will use a mixed-method approach incorporating a self-completed questionnaire, objective measures of physical activity, anthropometry assessment and focus groups. The findings will provide valuable information for health promotion, schools and city councils and will inform future interventions for built environment change, education campaigns, school policy development and city policy development.

Heuristics in the supermarket: Do food labels support healthy choices?

Dr Ninya Maubach (Marketing)
Other Otago Named Investigator:
Professor Janet Hoek (Marketing)

Rates of obesity and diet-related preventable diseases, including cancers and type II diabetes, are rising and require urgent attention. Although improving the healthiness of people’s diets is paramount, only a minority of consumers read objective nutrition facts panels, and research suggests shoppers are being misled by nutrition-related information elsewhere on food labels. Conflicting empirical results and unclear evidence of how labels influence behaviour have confounded regulatory progress, leaving a serious public health debate unresolved.

The proposed mixed-methods studies will provide the first insights into how consumers routinely use packaging information. Mobile eye-tracking technology will capture consumers' use of food labels in purchase decisions, which will be probed using in-depth interviews. These results will enable development and testing of alternative front-of-pack nutrition labels using innovative experimental research methods that overcome prior studies' limitations, and will provide the basis for food labelling that is currently failing to promote healthy choices.

Imaging markers of imminent cognitive decline in Parkinson’s disease

Dr Tracy Melzer (Medicine, Christchurch)
Other Otago Named Investigator:
Professor Tim Anderson (Medicine, Christchurch)

Most Parkinson’s disease (PD) patients eventually develop dementia, which is the most burdensome aspect of this progressively worsening condition. Mild cognitive impairments often indicate imminent dementia, but the 2 to 20 year time course poses a major problem for medical interventions, as brain changes associated with dementia in PD are still poorly understood. Recent evidence, however, suggests that neurodegenerative diseases such as PD progress along discrete brain networks. One important network, known as the ‘default mode network’ appears particularly susceptible to neurodegeneration. We will examine this network to determine if its disruption can specify which PD patients are vulnerable to progression to dementia within the next two years. A sophisticated but readily available brain imaging technique, called resting state functional imaging, will be used. These measures will assist in the selection of the most suitable patients for new treatments that may delay or prevent subsequent dementia in this vulnerable population.

Māori Disability Outcomes: Pathways and experiences after injury

Dr Emma Wyeth (Preventive & Social Medicine)

Injury-related disparities exist between Māori and non-Māori. For example, Māori hospitalised as a consequence of injury have 70% increased risk of disability compared to non-Māori – yet the reasons for this disparity are unknown. Using mixed methods, the aims of this study are to understand the pathways and experiences for Māori who were hospitalised after injury and to identify factors that contribute to disability. New analyses will be undertaken of data already collected from detailed questionnaires in a study of outcomes for injured New Zealanders (566 Māori and 2290 non-Māori). Face-to-face interviews will be undertaken with Māori hospitalised as a result of injury and experience profound disability 24 months later (n=27). The research team will work closely with key advisors with expertise in Māori health and disability to meaningfully interpret study findings. Key points in the injury and rehabilitation pathway will be identified warranting further attention to improve outcomes.

A list of Otago experts available for media comment is available elsewhere on this website.

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