Research
   
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Research projects Overview of research initiatives
The major research areas that have received support from the Foundation are notably:
Arrow funds research into degenerative intervertebral disc disease Catalina Palma - Arrow/HCC Research Scientist Mark Lutherborrow - Arrow/HCC Senior Research Scientist, 2009 St Vincent's Hospital Blood Cancer and Stem Cell Transplant Research Unit Zinc Finger protein (ZNF80) - 'Gene Switch' by Professor David Ma Gene Control in Acute Leukaemia by Professor David Ma Publications and Presentations Arrow funds research into a likely breakthrough for severe degenerative intervertebral disc disease Severe degenerative intervertebral disc (IVD) disease is an incurable condition and a major cause of harsh back pain. It has been demonstrated that human bone marrow stem cells (BMSCs) can survive when transplanted into the IVDs of rodents. Researchers from the Blood Stem Cell & Cancer Research Unit at St Vincent's Hospital, Sydney, and the Orthopaedic Research Institute, St George Clinical School, UNSW, have also shown that these disc like cells can be generated from BMSCs in culture flasks. As it is Arrow's mission to foster research into diseases treatable by bone marrow and stem cell therapy, a funding grant of $40,000 has been approved by Arrow's Executive Committee to support this very promising research project which is now at the exciting stage of transplanting the disc like cells into rodents to test their potential to repair damaged IVDs. This new study is part of an adult stem cell programme and hopes to benefit thousands of patients with severe lower back pain. Arrow-HCC Research Scientist - Catalina Palma 
Catalina studied neuroscience at UNSW and completed her honours degree at the Prince of Wales Medical Research Institute where she studied nerve regeneration. She then completed her PhD in Haematology Research at the Prince of Wales Hospital under the supervision of Associate Professor Robert Lindeman and Professor Bernie Tuch. There she studied the ability of blood stem cells to be turned into insulin producing cells which could one day be a therapy for type 1 diabetes. Catalina joined Professor David Ma's team in September 2009 to work along with Mark Lutherborrow (former Arrow-HCC Research Scientist), Adam Bryant (former Arrow-HCC PhD scholar) in the study of the genetic regulation of leukaemia. Catalina has focused her research on the role of small regulatory genes (microRNAs) in Acute Myeloid Leukaemia. Using genetic manipulation technology, Catalina has found evidence how these genes contribute to the uncontrolled growth and inability of leukaemic cells to mature and die. The aim of the team is to pinpoint the exact action of these genes resulting in leukaemia and the knowledge gain will advance the diagnosis and treatment of the disease. In the last year the team has had their research accepted for publication in the journal 'Molecular Cancer' and they also published a review article detailing the role of microRNAs in the development of blood cells and their transformation into cancer. In the same year, Catalina, on behalf of the team, presented four papers in two prestigious conferences, the Combined HAA meeting in Sydney and the American Society of Hematology Meeting in San Diego, USA. Mark Lutherborrow - Arrow/HCC Senior Research Scientist, 2009
Mark completed his honours degree in 2000 from the University of Technology Sydney and then worked for nine months at the Heart Research Institute at Royal Prince Alfred Hospital. The project he worked on investigated the immune system's contribution to the development of heart disease. From there he worked for a year at the Diabetes Transplant Unit before starting his PhD in late 2002 (completion early 2007) under the supervision of Professor Bernie Tuch. Mark's PhD project was centred on investigating those genes involved in the storage of insulin. His lab had developed insulin-producing liver cells as a potential therapy for type 1 diabetes, and his work from his Doctorate involved characterising and improving the secretion of insulin from these cells. Mark joined the St Vincent's Hospital Haematology Research Group in November 2006, to work with Professor David Ma and To Ha Loi on the gene profiling projects. These projects aim to further characterise various leukaemia and Lymphoma cancers at a gene expression level. They hope that the characterisation of these cancers will lead to an improved understanding of the cancer, with the potential to advance the diagnosis, prognosis and response to treatment.
St Vincent's Hospital Blood Cancer and Stem Cell Transplant Research Unit
A major research facility of the St Vincent's Healthcare Campus Sydney, the Unit focuses on the clinical application of research into blood cancers and blood related diseases. Research is under the direction of Professor David Ma who, with other doctors contributing to research, is involved in day-to-day patient care. The Unit supports the hospital's diagnostic and treatment as well as clinics in regional centres of New South Wales. The current research emphasis is on identifying abnormal genes to gain a better understanding of what causes diseases and, importantly, how better to treat or prevent them. Examples are:
This project aims to establish a reliable molecular genetic assay that can be applied to the management of patients receiving bone marrow transplants from matched donors (allogenic transplants). A successful bone marrow transplant depends on the ability of the donor's bone marrow stem cells to establish themselves within the patient (engraftment). Commonly used gene markers cannot be used to detect engraftment because most donors and patients are matched to be as similar as possible. Microsatellite DNA, however, is highly variable between individuals, and is even different in identical twins. It is thus a suitable method to detect the amount of donor bone marrow cells in the patient. This goal was accomplished in 2003 and has been tested in the clinic. This project utilises cutting edge gene chip technology in the fight against leukaemia and lymphoma. Although a human cell contains 40-50,000 genes, only a fraction are activated in a co-ordinated manner at a single point in time. Current molecular techniques can only detect a handful of activated genes in a single experiment, whereas DNA microarray technology has the ability to simultaneously detect over ten thousand activated genes. This provides a powerful tool to interrogate the cellular pathways of both normal and cancer cells. The aim of this project is to use this technique to improve the diagnosis of blood cancers and to better define the variability within leukaemia and lymphoma. We have established this new technology in our research unit and initial experiments on tumour samples have shown promising results. Future work will focus on discovering new drugs and tailoring treatment for individual patients. Zinc Finger protein (ZNF80) - 'Gene Switch' by Professor David Ma A Zinc Finger protein is a transcription factor (Gene Switch), which belongs to a group of proteins that function by controlling the expression of other proteins. Professor David Ma and his team at St Vincent's Hospital discovered a link between the Zinc Finger protein and a key protein involved in the "self-eating" (autophagy) of the cell. After a number of experiments, the team looked at the role of the protein in malignant cells and concluded that autophagy, or "self-eating", is involved in the resistance of myeloma cells to treatment. The Zinc Finger protein is therefore critical to the survival of myeloma cells. Research will now centre on dissecting pathways and mechanisms that are crucial to the action of the Zinc Finger protein leading to drug resistance and survival of cancer cells. Gene Control in Acute Leukaemia by Professor David Ma Recent research in acute leukaemia has discovered that acquired gene changes, known as mutations, can lead to excessive cell growth or inhibit normal cell maturation resulting in bone marrow failure and death. However, these mutations only provide part explanation of the leukemic process. This shortcoming represents a significant gap in our understanding of acute leukaemia. MicroRNAs are newly discovered small genes that regulate vital cellular functions and have been found to be involved in the development of prostate and bowel cancers. This new research proposal is the result of research in the last two years whereby genetic profiling of acute leukaemia using gene chip technology identified several microRNAs that are linked with unique subtypes of acute leukaemia. We aim to examine how these tiny genes may promote cell growth and inhibit maturation of bone marrow stem cells leading to the development of acute leukaemia. This research may result in better understanding of the biology of this rapidly fatal cancer and, in turn, may help to discover new tests and drugs to improve cure rates for patients. Mini-transplants: new report By Dr Adam Bryant, current Arrow/HCC PhD Scholar. At the Haematology Society Annual Scientific Meeting held in Adelaide last October, Arrow PhD scholarship recipient, Dr Adam Bryant, presented the findings of a retrospective analysis looking at outcomes for the growing number of patients receiving so called 'mini-transplants' in Australia and New Zealand. The intention with 'mini-transplants' is that they may reduce the toxicity of pre-transplant conditioning in patients that may otherwise not be able to tolerate full myeloablative conditioning (full Haemapoietic Stem Cell Transplantation), but where transplantation remains the only realistic option for a cure of their haematological disorder. Patients for whom 'mini-transplant conditioning' may be required include those: in older age brackets, with decreased performance status or other concurrent medical problems. The analysis, entitled 'Fludarabine Melphalan (Flu/Mel) Reduced Intensity Conditioning (RIC) in Australia and New Zealand; 1998 - 2008', revealed a steady increase in the use of 'mini-transplantation' (also known as RIC transplants), which now accounts for 30-40% of our total allogeneic transplant numbers. Approximately 60% of 'mini-transplants' utilised a conditioning regimen incorporating fludarabine and melphalan (Flu Mel), meaning that it is by far the most commonly used conditioning regimen for a 'mini-transplant'. In total, outcomes of 239 patients were analysed. Since it is not really appropriate to compare the outcome of patients with myeloid versus lymphoid diseases, each group was analysed separately. Demographic data confirmed that in practice, patients receiving 'mini-transplants' were older than patients receiving full HSCT (median age 49 lymphoid and 55 myeloid), with the older age of the myeloid patients reflecting the fact that there tend to be fewer alternatives to transplantation in patients in this patient group. The 100 day transplant related mortality was 11.7% for the lymphoid and 12.7% for myeloid patients (difference not statistically different) which is acceptable given the higher risk status of this cohort undergoing 'mini-transplantation'. There was good platelet and neutrophil engraftment, and acute graft versus host disease at acceptable limits. Overall survival rates show that the outcome for patients treated with Flu-Mel 'mini-transplants' in Australia/New Zealand was favourable and certainly comparable with published data from major international centres. It can be concluded from this analysis that Flu/Mel conditioning is a manageable and practical regimen for our transplant units and has efficacy for lymphoid and myeloid malignancies in older and high risk patients. Its continued use is now backed by an evidence based assessment. In 2011, the Hawkesbury Canoe Classic (HCC) generously funded Arrow's purchase of the following pieces of medical research equipment for the Blood Stem Cell and Cancer Research Unit, Department of Haematology & Bone Marrow Transplantation, St Vincent's Hospital, Sydney (SVH):
Research into the early detection, better treatments and ultimately a cure for leukaemia depends on accuracy and precision, so Arrow supporters also contributed to the purchase of a Pipette Set for the precise handling of liquids used in research. When peripheral blood stem cells (needed for transplant) are collected on the Cobe Spectra machine, they need to be separated from the collection kit in a sterile fashion. A 'heatsealer' achieves this and ensures the stem cells are viable for transplant. With the generous support of Michelle Hilton-Vernon and John Vernon, Arrow has purchased the first of the latest model to be released in Australia and has donated it to the Bone Marrow Transplant Laboratory at St Vincent's Hospital where 71 peripheral blood stem cell collections were performed last year. The new model is smaller and more lightweight than previous models.
As new concepts are developed and discoveries made, we will continue to improve our understanding, diagnoses, and treatment of blood cancers in our endeavour to cure leukaemia and lymphoma. For example, for the Microsatellite DNA Project (see section 4.2.2), the research scientists supported by the Foundation are currently refining the use of next generation genetic markers (SNPs) for donor cell detection by using a more sensitive and rapid method which will likely aid doctors in treating their patients. In the gene profiling research project, our research scientists are currently utilising a newer gene chip platform and commence collaboration with a bioinformatics group with the aim to extract reliable and important information from the data generated.. In the area of Bone Marrow transplantation, researchers at Department of Haematology and Bone Marrow Transplant, St Vincent's Hospital are conducting clinical studies in the use of bone marrow transplant to treat patients with autoimmune diseases such as scleroderma. The results from our initial clinical trials in rheumatoid arthritis and scleroderma have encouraged exploration of the use of bone marrow stem cells as a potential source of replacement therapy in neurological diseases, orthopaedic disorders, and heart diseases. The use of gene chips will be an integral part of the project. 
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