More than $1 million for medical research

04 July 2014

Medical researchers at the University of Auckland have been awarded just over $1 million in funding for research projects in the first round of grants this year from the Auckland Medical Research Foundation.

 “It was really pleasing to see such great research projects and talent across the full spectrum of medical science,” says the Foundation’s Executive Director, Kim McWilliams.  “More research is the only way we can ensure genuine advances in medicine and outcomes for patients.”

She acknowledged the Kelliher Charitable Trust, as a new funding partner that had enabled the Foundation to distribute two valuable new Emerging Researcher Start-up Grant Awards to the top two Fellowship recipients.

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.

The AMRF grants to University of Auckland researchers totalling $1,040,801 were:

MRI as biomarker for rheumatoid arthritis ($159,560 – 2 years); Professor Fiona McQueen, Dr Peter Chapman, Associate Professors Nicola Dalbeth and Anthony Doyle, and Dr Karen Lindsay.  Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences (FMHS).

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); Dr Lynsey Cree, Professors Larry Chamley and Peter Stone, and Dr Matthew VerMilyea. Department of Obstetrics and Gynaecology, FMHS.

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.

The role of intracellular ages in the diabetic heart, ($159,335 – 2 years), Dr Kimberley Mellor, Distinguished Professor Margaret Brimble, Professor Lea Delbridge.  Dept of Physiology, FMHS.

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 per cent 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) Dr Yongchuan Gu, Professor Peter Browett, Dr Frederik Pruijn, and Professor William Wilson, Auckland Cancer Society Research Centre, FMHS

The anticancer prodrug PR-104, developed at 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 left ventricular dyssynchrony assessment ($125,014 – 2 years), Dr Avan Suinesiaputra, Professor Alistair Young, and Associate Professor Brett Cowan. Department of Anatomy with Radiology, FMHS

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 per cent 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) Dr Jonathan Sperry, School of Chemical Sciences.

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. 

They 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) Dr David Musson, Mr Brendan Coleman, Professor Jillian Cornish, Dr Dorit Naot, and Dr Matthew Street, Department of Medicine, FMHS

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.

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

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) Pharmacology, Research support for her Edith C Coan Research Fellowship "Functional Characterisation of Cannabinoid Receptor SNPs Implicated in Mental Illness"

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

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 the Foundation has distributed more than $50 million in funding to a wide range of research activities – around $3-4 million annually.

The Foundation is unique in the charity sector, in that every dollar donated from within the community goes directly and fully to research. Administration costs are generously supported by a benefactor.

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