Funded Research

2018 Funded Projects

Congratulations to the successful applicants in this year’s Major Projects Round. Once again, the caliber of applicants was very high and our sincere thanks go to our Scientific Advisory Committee led by Dr Ben Hudson, who take significant time out of their research and clinical work to assess all incoming applications for us.

 

 Dr Andrew Das (University of Otago, Chch) 
 Developing tools to identify ascorbate-responsive subgroups of acute myeloid leukaemia

Acute myeloid leukaemia (AML) is a particularly aggressive form of blood cancer. Chemotherapy and  bone marrow transplant can result in a period of clinical remission, but overall only 20% of patients  survive for more than 5 years. Furthermore, many patients do not respond to chemotherapy at all,  indicating that new treatment strategies are needed.

Many of the early genetic changes in the development of AML affect epigenetic regulation, with effects that are potentially reversible. A prime example is the epigenetic regulator TET2, a protein whose activity is affected in up to one third of AML patients. TET2 requires vitamin C (ascorbate) to function, and patients with decreased TET2 activity could benefit from ascorbate supplementation. Recent studies using mouse models support this hypothesis.

However, patients with TET2 mutations always have additional mutations, which can greatly affect response to treatment. The effective design of future clinical trials relies on targeting the right treatment to the appropriate combination of mutations. Therefore, we will develop AML cell lines that combine TET2 mutations with additional mutations seen in patients to investigate their response to treatment with ascorbate. These cell lines will be invaluable tools for identifying subgroups of AML patients that could respond to ascorbate.

 

 Dr Rachel North (University of Canterbury) How does Haemophilus influenzae import sialic acids from the human host?

Despite advances in prevention and treatment, bacterial infections remain a global public health challenge largely due to the emergence of antibiotic resistance. Thus, there is a critical need for the identification, validation and molecular understanding of new targets for antimicrobial design. To combat the development of antibiotic resistance, one strategy for antimicrobial design is to specifically target virulence factors that are essential for infection.

Pathogenic bacteria rely upon scavenging nutrients from their host. This requires that the nutrients be transported across the bacterial cell membrane, a semi-permeable barrier that separates the bacterial cell from its environment. Transport is a tightly controlled process, mediated by specialised transporter proteins embedded within the membrane.

As a model system, we aim to unravel how a transporter protein embedded in the membrane of Haemophilus influenzae imports a simple sugar (sialic acid) into the cell. H. influenzae is an antimicrobial resistant pathogenic bacterium responsible for a range of illnesses in Canterbury and New Zealand. An inability to import sialic acid decreases H. influenzae virulence, but the molecular details of how this transporter works are not known. Byaddressing this gap in our knowledge, this work delivers a molecular understanding of a bacterial virulence factor.

 

Dr Yue Pei (University of Canterbury) Improving Memory

Ageing produces a decline in memory. Age-related degeneration, for example in Alzheimer’s disease, produces a devastating loss of memory. There has been a growing recognition that memory loss is associated with declining function in the brain’s “retrosplenial cortex”. This region is located at the back of the brain, near the midline in each hemisphere. It is strategically located and has connections with many other brain regions associated with memory. Optogenetics, a gene-based therapy permitting highly targeted stimulation of specific neurons in a given region, may provide a basis of new treatments for memory impairment. Our project will use this technique to test the beneficial effects of stimulating the retrosplenial cortex in aged rats, as a model of memory decline in human ageing. We will use the theta rhythmic frequency, which is particularly associated with good memory performance in younger rats and so should improve memory in older ones. We will then determine whether this stimulation has the same effect when it is restricted to initial learning only or to recall only. This project could provide a basis for further research on new therapeutics to improve memory affected by dementia and various neurological conditions such as stroke or severe head injury.  

 

Dr Jodie Johnston (University of Canterbury) Inhibiting Menaquinone Biosynthesis and Biofilms in S. aureus

New Zealand has among the highest reported incidence of infections with the bacterium Staphylococcus aureus in the developed world. This bug causes a range of infections from common skin infections like boils, school sores and cellulitis, to infections associated with surgical implants like hip replacements, heart, bone and blood infections, toxic shock syndrome and pneumonia. These infections are often recurrent and increasing numbers are being caused by strains like methicillin-resistant Staphylococcus aureus (MRSA), which are resistant to nearly all known antibiotics. The ability of the bacteria to persist inside the human body is one of the key drivers for recurrent infections. This is helped by their ability to make biofilms, where they adhere together on a surface. During biofilm formation the bacteria sense a range of environmental cues and interpret these as signals to cluster. One of these signals is given by a small molecule called Vitamin K2 (menaquinone). This study aims to make inhibitors of the bacterial enzymes that make menaquinone to study how menaquinone affects biofilm formation which will lead to drugs to target and treat S. aureus infections and biofilms.

 

Dr Nina Dickerhof (University of Otago, Chch) Redox regulation of the cytokine MIF during inflammation

We have discovered that chlorine bleach produced by white blood cells can modify an important regulatory protein in the immune system called macrophage migration inhibitory factor (MIF). The site of modification lies in a key region of MIF, suggesting that the modification will have biological significance. We now want to determine if MIF modification occurs when white blood cells are activated during bacterial infections, and if modification changes the function of MIF. To determine if MIF modification occurs we will use mass spectrometry to look in fluid from the lungs of children with cystic fibrosis. This condition is associated with an accumulation of large amounts of white blood cells within the lungs, increasing the likelihood of detecting modified MIF. Also, the appearance of modified MIF may be a sensitive indicator of bacterial infection and the need for more intensive management. In collaboration with researchers in Germany, we will also develop tissue-imaging mass spectrometry methods to measure MIF modification in a range of other diseases. This research may reveal a new marker of inflammatory disease, and also provide insight into a novel mechanism for regulating the immune response.

 

Dr Katie Douglas (University of Otago, Chch) Social Rhythm and Bright Light Therapy for Bipolar Disorder

The most common approach to treatment of bipolar disorder (BD) is medication. There is good evidence that evidence-based psychotherapies also add to treatment efficacy. However, they are relatively rarely used because of resource issues. Some people with BD do not respond well to standard medication treatment (‘treatment resistance’). In this case, psychotherapy is clearly indicated, but seldom available.

Disturbance in circadian and social rhythms is an important feature of BD and is more marked in patients who do not respond to treatment. Social Rhythm Therapy is a short psychotherapy which aims to address disturbance in circadian rhythms. The incorporation of Bright Light Therapy into this psychotherapy may have added benefit in stabilising sleep-wake cycles.

This study will be an open-label, pilot study to determine whether a modified version of Social Rhythm Therapy for treatment-resistant BD, as well as Bright Light Therapy (SRT-TR + Bright Light), is effective in improving mood, social rhythm stability, cognitive and general functioning, and quality of life. Twenty patients with treatment-resistant BD will receive SRT-TR + Bright Light over a 12-week treatment period, with weekly individual therapy sessions and daily bright light exposure. Findings will help inform larger-scale studies of adjunctive chronobiological treatments for BD.

 

 Dr Tracy Melzer (University of Otago, Chch) The hippocampus in Parkinson's disease

Parkinson’s disease currently affects 10,000 New Zealanders and this number is predicted to double over the next 25 years. In addition to motor impairments, many people with Parkinson’s develop cognitive problems and, eventually, dementia. We need to identify suitable objective tools that measure the underlying brain changes associated with cognitive decline. Such tools are important clinically and for assessing new preventative treatments. In this study, we will use comprehensive cognitive testing and brain imaging data to investigate the hippocampus, a key brain structure involved in memory. Leveraging our rich 10-year longitudinal study of cognition in Parkinson’s disease, we will specifically investigate (1) how the hippocampus changes over time in Parkinson’s disease and (2) whether brain imaging metrics from the hippocampus (including volume, blood flow, and white matter integrity) allow us to predict change in cognition (i.e., future cognition) in a clinically meaningful way. 

 

Dr Elisabeth Phillips (University of Otago, Chch) The role of microRNAs in fat-breast cancer cell crosstalk

Obesity is associated with worse outcomes in patients with breast cancer. One reason for this is that breast cancer cells and fat cells interact at a local level, within the breast tumour. This crosstalk between breast cancer cells and the fat cells intensifies during obesity, and promotes breast cancer cell metastasis and resistance to anti-cancer therapies. MicroRNAs are small regulatory molecules that help turn genes on and off in cancer cells. Within breast tumours, microRNAs target specific genes that, in turn, alter the breast cancer cell phenotype so they become more metastatic and resistant to anti-cancer therapies. Our project aims to identify microRNAs associated with fat-breast cancer cell crosstalk and discover how they may promote breast cancer metastasis and resistance to anti-cancer therapies. We have exciting preliminary data indicating that breast cancer cells cultured alongside fat cells have altered microRNA expression profiles. Using cutting edge molecular techniques, we will (1) identify the microRNAs involved, (2) discover their down-stream gene targets and (3) test whether altering microRNA levels can modulate breast cancer cell migration, invasion and response to anti-cancer therapies. This study has the potential to identify new targets for breast cancer therapy, particularly in obese patients.

 

 

 


2017 Funded Projects

Dr Khoon Lim (University of Otago, ChCh) Engineering Cartilage Constructs using 3D Bioassembly 

Articular cartilage has a limited regenerative capacity, and few approaches employed are clinically capable of restoring long-term function. This research is focused on bridging the gap between regenerative medicine and the clinic by developing improved cell therapy strategies and advanced 3D printing scaffold technique for repairing damaged cartilage.

 

 

 

Dr Cameron Lacey  (University of Otago, Christchurch)  Pilot RCT of Activation Therapy for Inpatient Depression 

Patients with severe depression who require admission to an psychiatric unit usually have serious impairment in many areas of functioning, particularly cognitive function (memory, concentration, planning). We have designed Activation Therapy (AT), a package of psychological treatment combining cognitive activation (targeted computerised cognitive exercises to improve cognitive performance) with behavioural activation (scheduling and encouraging activity to improve mood). We believe this treatment package may improve outcomes for in-patients with depression, particularly cognitive functioning and general functioning, may speed up mood recovery and reduce the likelihood of re-admission.

 

 

Dr Martina Paumann Page   (University of Otago, ChCh)  Assay development for a protein implicated in metastaticmelanoma

Peroxidasin is a protein found in most tissues in the human body. Its physiological function was discovered only recently and so far its contribution to health and disease is poorly understood. There is evidence that peroxidasin plays an adverse role in certain pathologies. Peroxidasin was shown to be upregulated in numerous types of tumors. Moreover it was identified to be vastly elevated in metastasizing melanoma skin cancer cells. Peroxidasin also appears to be involved in tissue fibrosis. Peroxidasin is a protein found in most tissues in the human body. Its physiological function was discovered only recently and so far its contribution to health and disease is poorly understood. There is evidence that peroxidasin plays an adverse role in certain pathologies. Peroxidasin was shown to be upregulated in numerous types of tumors. Moreover it was identified to be vastly elevated in metastasizing melanoma skin cancer cells. Peroxidasin also appears to be involved in tissue fibrosis. 

However, the underlying molecular mechanisms are largely unknown. To date there are no assays available to detect peroxidasin protein and activity. To study the involvement of peroxidasin in melanoma we will develop specific methods to measure peroxidasin in various biological samples, therefore providing important tools to improve our understanding of the reactions of peroxidasin and its implications in health and disease.

 



Ms Jennifer Crowther (University of Canterbury) Towards the development of a bioassay for the early detection of pre‐eclampsia 

Pre-eclampsia, a hypertensive disorder, is a potentially life-threatening condition that develops in 2 – 7% of all pregnancies worldwide. Currently, the only option in severe cases is the early delivery of the baby. Symptoms usually subside for the mother within days of giving birth, but early delivery comes at the expense of the health, or even life, of the child. Earlier intervention strategies allows prolongment of the pregnancy, improving health outcomes for the mother and baby.

 

 


Dr Nicola Scott   (University of Otago, ChCh) Phosphodiesterase 9 inhibition as a novel therapeutic strategy in heart failure

Heart failure (HF) remains a leading cause of death and disability in New Zealand, and new treatments are needed. The natriuretic peptides (NPs) are hormones whose actions alleviate the symptoms of HF and delay its progression.Regulating the activity of the NPs is phosphodiesterase 9 (PDE9), an enzyme that reduces NP signalling and is elevated in HF in association with blunted NP activity. With increasing evidence indicating PDE9 contributes to HF worsening, we hypothesise that inhibition of the PDE9 enzyme will restore NP efficacy with resultant beneficial effects. Our research aims are to explore PDE9 inhibition as a treatment strategy in HF.

 

 

Dr Sarah Appleby  (University of Otago, ChCh)  Myoregulin: a secret code underlying heart disease

Cardiovascular disease remains the leading cause of death in New Zealand, necessitating new biological markers that will aid in earlier diagnosis, treatment or prognosis. Recently, a potential untapped source of these markers has arisen from what was previously thought of as “junk DNA”, but has now been found to produce functional proteins. This project will explore one of these novel proteins, myoregulin, which is thought to control calcium levels in muscle cells. Keeping calcium levels balanced in the heart is extremely important for normal heart functioning, thus, myoregulin may be an important regulator of heart function.

 

 

 

Dr Patrice Rosengrave   (University of Otago, ChCh)  The effect of vitamin C administration on long-term physical and mental health outcomes of survivors of sepsis.

Sepsis is a life-threatening condition that is widely defined as a systemic inflammatory response to severe infection resulting in multi-organ failure, and is leading cause of mortality in critically ill patients. Many survivors of sepsis have substantial long-term physical, cognitive, and psychological impairments, also known as Post Intensive Care Syndrome. Our data indicates that patients with sepsis have very low vitamin C levels. Previous studies in cancerpatients have highlighted the role that vitamin C plays in improving patients’ quality of life. Therefore, we hypothesise that vitamin C administration to survivors of sepsis after discharge from hospital will aid in their recovery by improving physical functioning and performance, as well as their mental health. 

 

 

2016 Funded Projects

Dr Anitra Carr  (University of Otago) Intravenous Vitamin C and severe sepsis outcomes - randomised controlled trial              

Sepsis and septic shock are caused by a systemic inflammatory response to severe infection that results in multiorgan failure and refractory hypotension. The incidence of severe sepsis is increasing and is the leading cause of mortality in critically ill patients. Preliminary data indicates that sepsis results in significant depletion of vitamin C levels and a recent Phase I study demonstrated that administration of vitamin C to patients with severe sepsis dramatically improved inflammatory biomarker levels and clinical outcome measures. Vitamin C acts as a cofactor for numerous regulatory and biosynthetic enzymes, including those responsible for vasopressor synthesis. Therefore, we hypothesise that vitamin C administration will improve sepsis-related disorders such as hypotension through its enzyme cofactor activities. This Phase II randomised controlled trial will assess the effects of vitamin C infusion on hypotension and vasopressor requirements, as well as markers of oxidative stress, inflammation and leukocyte activity, in patients with severe sepsis. The biochemical mechanisms of action will be determined by measuring a suite of clinically-relevant and novel cofactor activity biomarkers. Overall, this study will establish the efficacy of vitamin C in improving clinical outcomes in the critically ill. You can read Anitra's full research profile here and her final report here

 

 

Dr Rachel Purcell  (University of Otago) Contribution of enterotoxigenic Bacteroides fragilis to colorectal carcinogenesis                               

Colorectal cancer is a common type of cancer, and while recent evidence suggests that gut bacteria may increase risk, the exact mechanisms remain elusive. Bacterial infections can cause chronic inflammation, which has been linked to cancer development. The Bacteroides fragilis toxin potentially alters intracellular signalling pathways that are also linked to cancer development. We will explore how chronic inflammation as a result of enterotoxigenic B. fragilis (ETBF) infection is associated with development of colorectal cancers, including whether genetic mutations arise as a result of this chronic inflammation. We will also investigate the role of microRNAs as a potential mechanism that regulates this process. MicroRNAs are small RNA molecules that do not code for proteins, but have recently been shown to play important roles in many cellular processes, including the development of cancer. We hope that this project will identify novel markers for the early detection of colorectal cancer. You can read Rachel's full research profile here.

 

 

Dr Andree Pearson (University of Otago) Measurement of Mitochondrial Function during Human Ageing                                                                

Human life expectancy has increased considerably in the last century, but along with this advance has come the increased burden of age-related disease and disability. Interventions that promote healthy ageing are limited, and new advances will depend on improved understanding and measurement of the underlying biological processes. Mitochondria are the site in our cells where food is converted into energy. Mitochondrial dysfunction isclosely linked to ageing, however there is an absence of non-invasive methods for measuring mitochondrial function in humans. We will attempt to use new technology to measure the health of mitochondria in cells isolated from a small blood sample. We will compare mitochondrial function in an elderly population with that of a younger population, and also examine how effectively the antioxidant defences of ageing mitochondria cope with an oxidative stress. This project will provide insight into the biological processes underlying human ageing, and methodology to measure these processes in the general population.

 

                                                                                                                                                          

Dr katie Douglas (University of Otago) Pilot Study of Cognitively-Enhanced Interpersonal and Social Rhythms Therapy for Depression 

Major depressive disorder (MDD) involves significant morbidity, suicide risk, and recurrent hospitalisations. After recovery from a depressive episode, individuals often continue to experience problems with cognitive (i.e., thinking, organisation, memory) and general functioning, and report these problems to be distressing and disabling. Treatment of severe depression in New Zealand involves short-term treatment by Specialist Mental Health Services (SMHS) then discharge back to primary care. Following discharge, readmission to inpatient and outpatient services is very common. We are therefore interested in developing a treatment for people with severe depression that could be used to aid in cognitive and functional recovery following discharge from SMHS. You can read Katie's full research profile here.

 

                                                                                                                                                                                                    

 Dr Margaret Currie (University of Otago) Does exercise lower systemic inflammation and improve chemotherapy efficacy in cancer patients? 

Obese cancer patients tend to respond more poorly to chemotherapy and have more rapid disease recurrence and shorter survival times. One reason for this is that obesity leads to low-level chronic inflammation that fuels the development and spread of cancers. Little is known about how this systemic obesity-related inflammation affects the way cancer patients metabolise chemotherapy drugs. Therefore, this project aims to (1) measure circulating inflammatory proteins that may be used to identify patients who will respond poorly to chemotherapy and are at high risk of worse survival, (2) use cell culture studies to explore the way obesity-related inflammatory proteins may alter chemotherapy drug metabolism by the liver, and (3) perform an exploratory patient study that will use fitbits to monitor exercise during chemotherapy treatment, as well as measure circulating inflammatory proteins, patient liver enzyme activity and drug metabolism, and patient well being during treatment. This project will form the basis for ongoing studies at the University of Otago Christchurch into the potential benefits of moderate exercise during chemotherapy treatment. You can read Margaret's full research profile here.

 

 

                         

Dr Prisca Mbikou (University of Otago) Role and therapeutic potential of the novel DWORF peptide in heart disease

Heart disease (HD) is a leading cause of death and disability in New Zealand, and new treatment options are needed. A recent breakthrough in genetic research concerning so-called non-protein-coding RNA has led to the discovery of a new class of proteins, one of which is called dwarf open reading frame (DWORF). This small protein is found almost exclusively in the heart where it may cause increased contraction of the heart muscle. DWORF levels are decreased in the hearts of people who have had heart attacks, suggesting it plays a role in the development of HD and may have potential as a treatment for restoring the impaired beating of damaged hearts. However, exactly how DWORF works and the effect on the heart of directly administering the protein is unknown. The goal of this research project is to investigate the effect of DWORF on heart function in normal and damaged hearts (using an ex vivo rat heart attack model), its levels in the heart in both settings, what proteins it interacts with, and how it operates. These highly original studies will further our understanding of this unique protein and might help in the development of a novel treatment strategy for HD. You can read Prisca's full research profile here.

 

    

Dr Kristin Lamvik (University of Canterbury and Rose Centre for Stroke Recovery and Research) Reliability, validity and clinical application of temporal and amplitude analyses using pharyngeal highresolution manometry 

After stroke, the majority of patients will experience difficulties swallowing, termed dysphagia. This is a critical impairment as it can place patients at increased risk of developing chest infections or even facing an increased risk of death. Thus, the proposed research programme will provide directives for refining the use of evaluation tools in the clinical assessment of swallowing problems. This is will be done by investigating a technique termed manometry, which measures throat pressure when swallowing.

Manometry is important because it is one of the only ways to measure swallowing objectively, however, there is disagreement on the most valid and realiable way to analyse manometric data. The results from this study will have great importance both locally and globally. In Christchurch alone, there are two manometry systems used in clinical practice, one of which operates in the busy Christchurch Hospital. Thus, the results of this project will lead to an immediate improvement in patient care, helping to keep patients safe and swallowing effectively. You can read Kristin's full research profile here.

 

 

2015 Funded Projects

Major - Projects

 

Vitamin C requirements in Severe Infection - Dr Anitra Carr

Severe infection which results in a systemic inflammatory response (sepsis) is the leading cause of death in critically ill patients. The incidence of severe sepsis is increasing, and the outcome is poor, with mortality rates as high as 30-40%. Recent studies indicate a potential role for vitamin C in ameliorating severe infections (such as pneumonia) and sepsis. Vitamin C is a potent antioxidant and has potential anti-inflammatory properties. Preliminary research indicates that patients with sepsis have decreased vitamin C levels. The purpose of this study is to assess the levels of vitamin C in patients with pneumonia and sepsis over the duration of their stay in intensive care and to correlate these with levels of inflammatory biomarkers and patient outcomes. Vitamin C may prove to be a useful biomarker for the severity and progression of sepsis and the extent of deficiency of these patients will indicate requirements and will be used to inform the design of future clinical trials.

 

 

Red bloodcell vitamin C: a useful indicator of patient ascorbate status? - Dr Juliet Pullar

Vitamin C is an essential requirement of the diet in humans due to the evolutionary loss of the ability to synthesise it in the body. Vitamin C status is typically measured in a fasting-blood sample, which can be difficult for some people to provide, particularly those who are unwell. The aim of this project is to establish a method for measuring vitamin C status in non-fasting individuals using red blood cells. We will firstly optimize a procedure for assessing red blood cell vitamin C levels, and then measure the red blood cell vitamin C status of a group of surgical, sepsis and cancerpatients at Christchurch Hospital. Overall, this study will determine whether non-fasting red blood cell vitamin C levels are a reliable measure of patient vitamin C status.

 

  

 

The effects of resveratrol’s derivatives on VEGF, IL-6, IL-8 and NF-kB in ovarian cancer in vitro and in vivo studies -Dr Kenny Chitcholtan

Women with advanced ovarian cancer normally have a poor outcome because the tumour has spread within the abdominal cavity at the time of diagnosis. Most women with advanced disease show the sign of building up ofbody fluid; this becomes a clinical challenge for the current treatment management. Treatments currently available can prolong time of survival, but tumours become resistant to treatment and a cure is rare. In order to prolong time of patient survival, a new form of anti-cancer drugs, showing less side effects and being low cost, is urgently needed. Resveratrol is a food compound and has been found to show anti-tumour activity in a laboratory. But its anti tumour activities are uncertain in humans because resveratrol is highly metabolized and rapidly secreted from the body. Therefore, compounds that are structurally related to resveratrol may be useful to investigate their anti-tumour activities in human. We are very interested in derivatives of resveratrol and we want to investigate if these derivatives can exhibit anti-cancer activities in a laboratory before we could use them in humans.

 

 

RNA isoform profiling of breast cancer susceptibility genes - Dr Logan Walker

Routine diagnostic BRCA1 and BRCA2 gene screening for deleterious mutations is typically performed for individuals from suspected high-risk breast-ovarian cancer families to identify the genetic cause for their disease. However, for most women with breast and ovarian cancer, the genetic changes contributing to their disease remain poorly understood. High-throughput genomic technologies are now being adopted by diagnostic laboratories worldwide, enabling mutation screening of BRCA1 and BRCA2, and other cancer related genes in a greater number of people. Determining the clinical meaning of newly discovered genetic changes will be a central challenge facing the future of genomic medicine. We will apply two powerful new technologies to measure the expression behavior of BRCA1 and BRCA2 activity in breast tumours from patients with and without a strong family history of cancer. Our proposal will assess if the inherited mutation status of these genes disrupts their behavior. Furthermore, our proposal will generate the first comprehensive gene expression profile of BRCA1 and BRCA2 in familial and non-familial breast tumours. The new knowledge derived from this proposal may facilitate the development of genomic-based protocols to evaluate genetic changes responsible for breast cancer and other inherited diseases.

 

 

 

Mycoplasma genitalium macrolide and fluoroquinolone - Dr Anja Werno 

Mycoplasma species are the smallest free living bacterial forms. Mycoplasma genitalium is accepted as a human pathogen causing infections including urethritis and cervicitis. The first-line treatment of M. genitalium infections isazithromycin and in cases of treatment failure moxifloxacin is used. M. genitalium cannot be routinely cultured in the clinical laboratory and requires molecular techniques such as real-time PCR for detection and DNA sequencing to test for antibiotic resistance. The aim of this study is to evaluate whether the resistance rates warrant introduction of routine molecular resistance testing to assist with patient management. Monitoring of resistance rates will be useful to advise long-term treatment strategies around non-specific urethritis/cervicitis. 

 

 

Identifying candidate RNA biomarkers for coronary artery disease - Dr Anna Pilbrow

Coronary artery disease (CAD) is a very common form of heart disease and is a leading cause of death in Canterbury. CAD develops when cholesterol-containing deposits (plaque) accumulate in the coronary arteries. As plaques build up, they decrease the flow of blood to the heart muscle, which can cause chest pain or a heart attack. The rate at which plaques build up varies between people making it difficult to identify those who may be at risk of a heart attack in the near future. Our research aims to identify new blood biomarkers for the presence of coronary artery disease, to allow screening and early detection of those at risk. Specifically, we will use a high-throughput genomics technology called next generation sequencing to measure levels of a newly-discovered class of molecules called long noncoding RNAs in 12 patients with stable coronary artery disease and 12 healthy controls from Canterbury. This in-depth screening study will help us identify candidate biomarkers to test in our existing, large cohorts of healthy volunteers and CAD patients in the future. Ultimately, our research may contribute to the development of new blood tests that will help predict those at impending risk of a heart attack. 

 

 

 Pilot study of biomarkers of outcomes from anticoagulants - Dr Paul Chin

Dabigatran (Pradaxa®) is a relatively new blood thinner medicine that is used to prevent clots. It was used in over 2,000 Cantabrians in 2014, and over 15,000 nationally. The main side-effect is bleeding. Dabigatran is currently used without any blood tests to check for the level of blood thinning. High levels of blood thinning may lead to bleeding, whereas low levels may lead to clots and strokes. Our study aims to find the ideal level of blood thinning with dabigatran. We will do this by doing blood tests on people taking this medicine, including those having clots and bleeds, as well as those who are well. In the future, knowing the ideal level of blood thinning with dabigatran will enable dabigatran doses to be adjusted so that high and low levels may be avoided. 

 

 

 

C-Type Natriuretic Peptide and Renal Dysfunction - Dr Tim Prickett

Renal function is a major determinant of prognosis in patients presenting with heart failure or coronary artery disease. Recently we have discovered that fragments of a precursor molecule of C-type Natriuretic Peptide (CNP)are raised in blood as renal function begins to decline. Whether these changes result from diminished clearance or increased production by the kidney is unknown. The molecular identity of these peptide fragments and changes to their relative abundance in blood and urine in the failing kidney is unknown. The objectives of this proposal are twofold. Firstly, to identify the specific products of CNP gene expression in urine and plasma and thereby measure their clearance and renal production rates in health. Secondly, to measure both renal CNP production and clearance before, during and after induction of early renal and cardiac impairment induced by rapid ventricular pacing in 10 sheep. Collectively these studies will illuminate the mechanisms that lead to changes in CNP during the early phase of cardiac and renal impairment and may identify novel prognostic biomarkers suitable for detecting early renal failure (and implementing corrective treatments) in subjects with cardiovascular disease. 

 

 

Amyloid and cognitive predictors of dementia in Parkinson’s - Dr Tracy Melzer

Cognitive decline and dementia are now recognised as an essential part of Parkinson’s disease, which ultimately becomes the most burdensome aspect of this disease. We know that those exhibiting mild cognitive impairments are at increased risk for developing dementia, but we have established that some individuals not showing cognitive impairments also exhibit increased risk. Here, we will perform advance positron emission tomography (PET) and MRI scans, and clinical evaluation in Parkinson’s patients with both high and low risk for developing dementia. We will determine whether PET imaging adds further information about an individual’s risk of future dementia. This will 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. 

 

 

Pilot of methods to measure unmet secondary healthcare needs - Dr Phil Bagshaw

We have information on people who are treated in hospital but it is difficult to know how many people have health needs that are not being met. We know that some health services are over-crowded and that, over the last twenty years, a number of policies have limited peoples’ access to non-urgent care. This project will trial three population survey methods, and a method of getting information from GPs, to establish a reliable method of measuring unmet healthcare need in the community. We plan that in the future we will be able to measure unmet-need to assess the ongoing performance of the health system.

 

 

Special - Projects

 

An investigation into the possible linkages between Vitamin C, Hypoxia and Cancer in Breast Cancer. Proposed analysis of Human Breast Cancer Tissue. - Professor Margreet Vissers  (a jointly funded project with the NZ Breast Cancer Foundation)

The team will recruit breast cancer patients into future clinical studies, but first need to determine whether the inverse relationship between tumour ascorbate, the hypoxic response and tumour growth also applies to breast cancer. The team will carry out the analysis of a cohort of Tissue Bank breast cancer samples to determine whether the HIF-1 and ascorbate relationship exists in these tissues.

 

Projects Archive

Here you can read the final reports from most of the CMRF-funded projects from the past few years.

2017

Dr Logan Walker, University of Otago - RNA isoform profiling of breast cancer susceptibility genes

Dr Anitra Carr, University of Otago - Intravenous Vitamin C and severe sepsis outcomes - randomised controlled trial 

2016

Dr Dean Harris, Christchurch Hospital - Potential biomarkers of 5FU cardiotoxicity

Dr Heather Parker, University of OtagoSuperoxide dismutase and infection with Mycobacterium tuberculosis

Dr Louisa Forbes, University of Otago - Screening for Potent Inhibitors of Myeloperoxidase

Dr Katie Douglas, University of Otago - Effect of glucocorticoid administration on brain function in PTSD

Dr Philip Bagshaw et al, Canterbury Charity Hospital - Pilot study of Unmet Need

Dr Tracy Melzer, University of Otago - MRI to predict dementia in Parkinson's disease

Dr Daniel J Myall, University of Otago - Optimally predicting risk of cognitive decline in Parkinson's disease

Dr Jacqui Keenan, University of Otago - Unravelling the host innate response to enteral nutrition

Dr Suetonia Palmer, University of Otago - An evidence framework for protecting kidney function

2015

Dr Wanting Jiao, Canterbury University - Developing new drugs for lung infections in cystic fibrosis

Dr Katie Douglas, University of Otago - Effect of glucocortocoid administration on brain function in PTSD

Dr Amy Scott-Thomas, University of Otago - Development of a non-invasive breath test for Legionnaires Disease

Dr Stephanie Bozonet, University of Otago - Regulation of endothelial cell death by Hypothiocynous acid

Dr Nicola Scott, University of Otago - Understanding how food leads to fat: the effect of dietary modification on the development of metabolic syndrome

Dr Judy McKenzie, University of Otago - Activated chronic Lymphocytic Leukaemia cells: suppressive effects on T Cell responses

2014

Dr Carrie Innes, University of Otago, NZ Brain research Institute - Effect of obstructive sleep apnea on microsleeps and cerebral blood flow

Dr Tracy Melzer, University of Otago, NZ Brain Research Institute - Clinical tracking of cognition on Parkinson's Disease

Dr Logan Walker, University of Otago - Cytomegalovirus and Epstein Barr virus in Breast Cancer

Dr Lee Thompson, University of Otago - Role evolution and community pharmacy in Christchurch. Perceptions of pharmacists, GPs and pharmacy users

2013

Dr Gabi Dachs, University of Otago - Chemotherapy response in obese mouse model with colorectal cancer

Dr Nadia Borlase, University of Otago - Thalmus in Parkinson's Disease ; a multimodal investigation of thalmic invovlement in cognitive impairment

Dr Judith McKenzie, University of Otago - Analysis of immunosuppression in Chronic Lymphocytic Leukaemia cells

2012

Dr Claire Dowson, University of Otago - Cognitive / behavioural function in long term SSRI antidepressant use

2011

Dr Leigh Ellmers, University of Otago - Effect of Chronic Urocortin2 treatment following experimental myocardial infarction

Dr Lisa Stamp, University of Otago - Effects of Frusemide on uric acid and oxypurinol in patients with gout

2010

Dr Mark Richards, University of Otago - Renal impairment in decompensated heart failure

Dr Ruth Hughes, University of Otago - Screening for Type 2 diabetes in pregnancy

Dr Barry Palmer, University of Otago - Polymorphic variants of X-linked genes in heart disease

Dr Kenny Chitcholtan, University of Otago - Heliobacter Pylori outer membrane vescicles compromise the integrity of gastric epethelial cells

Dr Tim Woodfield, University of Otago - Alternative cartilage tissue engineering strategies; smart scaffolds and perfusion bioreactors

Dr Michael Sullivan, University of Otago - Validating biological markers for Hepatomblastoma: recovery of biomarkers (DNA and RNA) from parafin embedded tissues and development of tissue arrays

 2009

Dr Lisa Stamp, University of Otago - A Pilot Study of high dose allopurinol in the management of gout

Dr Judith McKenzie, University of Otago - Function of soluble CD83 in Chronic Lymphocytic Leukaemia

Dr Ross Kennedy, University of Otago - Determination of Effect site targets for Sevoflurane

Dr John Evans, University of Otago - Why do males die younger? Sex, steroids and yasopeptides

Dr Tim Prickett, University of Otago - NTpnoCNP as a marker of skeletal growth

Prof Margreet Vissers, University of Otago - A new role for Vitamin C in control of hypoxis response in cancer cells