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Auckland Medical Research Foundation Awards close to $1.5m

4 July 2014

Auckland Medical Research Foundation Awards close to $1.5 million to Medical Researchers for first half of 2014

The Auckland Medical Research Foundation (AMRF) has recently announced $1,320,066 in funding to medical researchers in the first three funding rounds for 2014.

Foundation Executive Director, Kim McWilliams says, “It was really pleasing to see such great research projects and talent across the full spectrum of medical science this half. More research is the only way we can ensure genuine advances in medicine and outcomes for patients. This half we acknowledge the Kelliher Charitable Trust, a new funding partner that has enabled us to distribute two valuable new Emerging Researcher Start-up Grant Awards to our top two Fellowship recipients”.

The successful grants included 9 research projects ($1,054,471), 2 Gavin and Ann Kellaway Medical Research Fellowships ($61,463), 2 Sir Harcourt Caughey Awards ($50,000), 36 travel grants ($94,132) for researchers to present their research overseas and 2 Kelliher Charitable Trust Emerging Research Start-up Awards($60,000). Grants were awarded over a variety of biomedical and clinical research areas including Biomedical Imaging, Reproduction, Development, Maternal and Newborn Health, Cardiovascular Science, Cancer, Infection and Immunity and Musculo-skeletal Science.

See Below for Project Summaries

The Auckland Medical Research Foundation is a major independent funding agency and charitable trust that provides contestable funding for medical research across the complete spectrum of modern medicine. Over the last 58 years we have distributed over $50 million in funding to a wide range of research activities – currently around $3-4 million annually.

Our Foundation is unique in the charity sector, in that every dollar donated from within the community goes directly and fully (100%) to research. Our administration costs are generously supported by a benefactor.

For further information on the current grants awarded and application forms for future grant rounds see our website at www.medicalresearch.org.nz

Project Grants Awarded May 2014

MRI AS BIOMARKER FOR RHEUMATOID ARTHRITIS ($159,560 – 2 years) 1114001
Prof Fiona McQueen, Dr Peter Chapman, A/Prof Nicola Dalbeth, A/Prof Anthony Doyle, Dr Karen Lindsay
Dept of Molecular Medicine and Pathology, University of Auckland
The management of rheumatoid arthritis (RA) has undergone a revolution in the past decade. New drug therapies can markedly reduce joint pain and many patients can achieve clinical remission with reduction in long-term joint damage. It is important to assess patients’ responses to different drug regimens. MRI scanning is an ideal imaging biomarker as it reveals inflammation affecting the lining of the joint (synovitis) and the bone beneath (bone oedema or BME) plus joint damage (erosions and cartilage thinning). The Auckland Rheumatology Imaging group has an established track record in MRI research in RA. We now plan to move our expertise into the clinical arena. New Zealand rheumatologists use specific drug regimens (conventional and biological), to try and achieve remission in a “Treat-to-Target” approach. They monitor patients’ progress using the Disease Activity Score (DAS) which quantifies joint inflammation clinically. The aim of this study is to obtain MRI inflammation scores (synovitis, BME, tenosynovitis) before and after each drug intervention, to see whether changes in MRI scores mirror changes in the DAS. We intend to compare MRI and DAS responses between 2 groups of patients: those receiving conventional disease-modifying antirheumatic drugs (cDMARDs) and those receiving biological therapies (bDMARDs).

A NON-INVASIVE TEST OF EMBRYO QUALITY ($120,285 - 2 years) 1114002
Dr Lynsey Cree, Prof Larry Chamley, Prof Peter Stone, Dr Matthew VerMilyea
Dept of Obstetrics and Gynaecology, University of Auckland
In vitro Fertilisation (IVF) is a commonly used technique for infertility and its use is rising due to women delaying child bearing. Annually 350,000 babies are born using this technique, however success rates are still low. Developing techniques to select the best embryo for transfer in order to maximise the likelihood of a healthy live baby represents one of the major challenges in reproductive medicine. Recent data suggests that embryos expel genetic material into the media in which they are cultured. This is a novel finding that has the potential to provide a non-invasive way to look at the genetic complement of the embryo. Current techniques used to do this are invasive and some may harm the embryo. Our research aims to investigate whether this genetic material, located within the media, can give meaningful data of embryo quality and whether it can be used to select only those embryos with the correct chromosomal makeup. This is particularly important for older women whose embryos are more likely to have an incorrect chromosomal makeup. Selecting embryos with the correct chromosomal makeup will increase IVF success rates. This novel research project has the potential to change the future of embryo screening in New Zealand and internationally.

EFFECTIVENESS OF FOOTWEAR IN PEOPLE WITH GOUT ($106,553 – 2 years) 5114003
Prof Keith Rome, A/Prof Nicola Dalbeth, Prof Peter Gow, Prof Peter McNair, A/Prof Alain Vandal
Dept of Podiatry, Auckland University of Technology
Gout is a major cause of musculoskeletal disability in Aotearoa New Zealand. Foot pain occurs in most people with gout. There is strong evidence that many people with gout wear inappropriate or poor quality footwear, and that ill-fitting footwear may contribute to further foot problems. We have shown in a recent feasibility study that footwear with good cushioning, motion control and adequate width reduces foot pain and disability in the short term. We propose a long-term randomised controlled trial examining the effects of a footwear intervention on foot pain and disability. The trial will assess the effect of standard podiatric care and a relevant footwear intervention against standard podiatric care only. The study findings will be used to make evidence-based recommendations regarding footwear intervention for people with gout.

THE ROLE OF INTRACELLULAR AGEs IN THE DIABETIC HEART ($159,335 – 2 years)
Dr Kimberley Mellor, Prof Margaret Brimble, Prof Lea Delbridge
Dept of Physiology, University of Auckland
In New Zealand, more than 200,000 people are currently diagnosed with diabetes and the burden falls disproportionately on the Maori and Pacific Island populations, with the prevalence and death rates approaching double those of Pakeha. Diabetic patients have 2.5-fold increased risk of heart failure. The prevalence of diastolic dysfunction in type 1 and type 2 diabetes is estimated to be as high as 40-75% without overt coronary artery disease. The myocardial origins of this vulnerability are poorly understood and effective treatment strategies are lacking. This study aims to establish that in diabetes – glycation of intracellular proteins in the heart is a pathology to target therapeutically. In characterising intracellular glycation as a novel component of diabetic cardiomyopathy, this project has potential to contribute a highly significant advance in knowledge in this field – and to prompt an innovative paradigm shift in thinking about causation of diabetic cardiopathology. It is anticipated that this research will translate into specific fundamental outcomes relating to the science and the treatment of heart failure in diabetic patients.

PROTEOMIC PROFILING OF PRODRUG-ACTIVATING ENZYMES IN LEUKAEMIAS ($158,973 – 2 years) 1114005
Dr Yongchuan Gu, Prof Peter Browett, Dr Frederik Pruijn, Prof William Wilson
Auckland Cancer Society Research Centre, University of Auckland
The anticancer prodrug PR-104, developed in the University of Auckland, was designed to be activated by reductase enzymes in tumours under conditions of low oxygen (hypoxia), which is a hallmark of tumours. During its evaluation in clinical trials with solid tumours, pre-clinical research identified a reductase, AKR1C3, which also activates PR-104 in the presence of oxygen. AKR1C3 is highly expressed in some leukaemias. Given that the bone marrow becomes hypoxic in advanced leukaemias, it was suggested that PR-104 might exploit both AKR1C3 and hypoxia, leading to a phase I/II trial of PR-104 in relapsed acute myeloid and lymphocytic leukaemias. The trial showed good although variable responses, but only limited evaluation of biomarkers was undertaken. We will develop a targeted proteomics assay for PR-104 reductases, using a powerful mass spectrometry approach that allows simultaneous quantification of large numbers of proteins in clinical samples. The assay will be optimised for bone marrow and blood samples from patients and its ability to predict metabolic activation of PR-104 will be evaluated. If successful, the assay will be used in subsequent trials of PR-104 in human leukaemias to assess its role in identifying responsive patients in a personalised medicine context.

MODEL-BASED LVD ASSESSMENT ($125,014 – 2 years) 1114006
Dr Avan Suinesiaputra, Prof Alistair Young, A/Prof Brett Cowan
Dept of Anatomy with Radiology, University of Auckland
Ventricular dyssynchrony is the main predictor for cardiac resynchronisation therapy (CRT), an invasive procedure that can dramatically improve the morbidity and mortality of patients with chronic heart failure. However, 30% of patients who undergo CRT do not receive any benefit due to the lack of appropriate selection criteria, including current assessment technique. We aim to develop a more accurate and reproducible left ventricular dyssynchrony (LVD) assessment method based on mathematical modelling of the left ventricle derived from cardiac MRI. We are also investigating a novel prognostic prediction method based on multi-dimensional analysis of shape, motion and auxiliary diagnostic information, such as scar tissue location and electrical timing. This project will provide a valuable clinical tool to assess ventricular dyssynchrony prior to CRT procedure.

SELECTIVE INHIBITORS OF MRSA PYRUVATE KINASE AS STRUCTURALLY UNIQUE, NEXT-GENERATION ANTIBIOTICS ($12,000 – 2 years) 1114007
Dr Jonathan Sperry
School of Chemical Sciences, University of Auckland
This research will have implications in the treatment of infections caused by antibiotic resistant bacteria. Successful collaborative efforts with The University of British Columbia (UBC) have identified a small molecule inhibitor of methicillin-resistant staphylococcus aureus (MRSA) pyruvate kinase (PK) that exerts this inhibitory activity selectively over human isoforms. We will use these preliminary results to guide the rational design of a focused compound library, which will be sent to UBC for further biological analysis against MRSA PK. By conducting several iterations of this synthesis/biological evaluation process, we will develop potent, selective inhibitors of MRSA PK well-suited for in vivo evaluation as structurally unique antibiotics that work on a novel biological target compared to existing therapies.

WHY ARE KNEE LIGAMENT SURGERIES FAILING IN YOUNG PEOPLE? ($159,171 – 2 years) 1114008
Dr David Musson, Mr Brendan Coleman, Prof Jillian Cornish, Dr Dorit Naot, Dr Matthew Street
Dept of Medicine, University of Auckland
Tears of the anterior cruciate ligament, an important stabiliser of the knee joint, are a significant clinical problem in active, young individuals, with surgeries costing over $18 million per year in New Zealand. Recent data has highlighted that patients under the age of 20 undergoing surgical reconstruction of their anterior cruciate ligament are more prone to re-tearing. This study aims to understand the biological mechanisms behind this phenomenon by comparing the mechanical strength, structure and gene expression profile of biopsies from patients under the age of 20 and biopsies from those over the age of 20 undergoing anterior cruciate ligament reconstruction.

TARGETING THE MECHANISM OF HOST RECOGNITION TO PREVENT BACTERIAL INFECTIONS ($53,580 – 1 year) 4114009
Dr Xue-Xian Zhang, A/Prof John Harrison, Dist. Prof Paul Rainey, Dr Stephen Ritchie
Institute of Natural and Mathematical Sciences, Massey University
With the widespread increase of bacterial resistance to antibiotics, new strategies to prevent and treat healthcare-associated infection are urgently required. This proposal addresses a crucial gap in our current understanding of how bacteria cause disease - namely, how pathogenic bacteria recognise vulnerable hosts for successful colonisation and immune evasion. To date, our research has focused on Pseudomonas aeruginosa, an environmental pathogen that causes a wide range of healthcare-associated infections and pulmonary infections in people with chronic lung diseases, particularly cystic fibrosis. Recent progress has led us to a novel hypothesis that P. aeruginosa recognises urocanate in human tissues and use it as a trigger for bacterial invasion. To test this hypothesis, we will develop the analytic techniques that are essentially required for the detection of urocanate in chemically complex human samples (e.g., sputum, urine and wound fluid). Next, we will screen ~200 specimens from patients with various diseases (including asthma, diabetes and cystic fibrosis) in order to identify the urocanate-containing tissues for further investigation into the association between urocanate concentration and predisposition to bacterial infection. The data will form the basis for the development of new strategies to prevent bacterial infection through interrupting the urocanate-mediated host recognition.

Gavin and Ann Kellaway Medical Research Fellowships

These fellowships are awarded to support senior medically qualified, or established medical research persons, who would gain value from further study abroad, or in furthering their research expertise and knowledge at an approved overseas research institution.

Dr Darren Hooks ($39,663) 1514001
Bioengineering Institute, University of Auckland
To extend research collaboration between the University of Auckland (Bioengineering Institute) and the University of Bordeaux (LIRYC Institute), France, in the field of cardiac rhythm management.

Dr Vickie Shim ($21,800) 1514002
Bioengineering Institute, University of Auckland
To develop a research collaboration between the University of Auckland (Bioengineering Institute) and the University of California, Berkley, USA, to develop a computational microscope for investigating cell matrix interactions in the achilles tendon for tissue engineering applications.

Sir Harcourt Caughey Awards

These awards are granted to researchers who may (i) be New Zealand graduates who are returning to a part-time appointment in Auckland; or (ii) be an Auckland-based New Zealand medical graduate who is deserving of assistance to train and perform research in a specific field overseas, especially where there is a deficiency in local expertise in that field; or (iii) be sufficiently prestigious in a particular field of medical knowledge and/or research to visit Auckland, normally for 3-4 weeks, to foster interest and research in that specialty.

Dr Cho Yui Bob Chan ($25,000) 2514003
Dept of Dermatology, Auckland District Health Board
Multicentre observational prospective study for the identification of prognostic factors in patients with mycosis fungoides/Sezary syndrome. St John’s Institute of Dermatology, London, UK.

Dr Philip Robinson ($25,000) 1514004
Dept of Medicine, University of Auckland
The effects of uric acid on fasting insulin, fasting glucose, type 2 diabetes and other components of the metabolic syndrome. University of Auckland.

Kelliher Charitable Trust Emerging Researcher Start-up Awards

These awards are granted to AMRF Fellowship recipients to provide working expenses to support their fellowship research and progress their academic careers.

Dr Natasha Grimsey ($30,000) 1714001
Research support for her Edith C Coan Research Fellowship "Functional Characterisation of Cannabinoid Receptor SNPs Implicated in Mental Illness"

Dr Clare Reynolds ($30,000) 1714002
Research support for her David and Cassie Anderson Research Fellowship "Maternal Diet Induced Programming of Offspring Immune Function"

ENDS

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