Overview of research initiatives

The major research areas that have received support from the Foundation are notably:

• Graft-versus-host-disease (the major cause of death in post transplant patients);
• Bone marrow stem cell biology and its potential clinical applications; and
• Molecular biology of leukaemia and lymphoma.

 

Arrow funds research into degenerative invertebral disc disease

Mark Lutherborrow - Arrow-HCC Senior Research Scientist

St Vincent's Hospital Blood Cancer and Stem Cell Transplant Research Unit

Microsatellite DNA Project

Gene Chip Project

Future Research

Publications and Presentations

Arrow funds research into a likely breakthrough for severe degenerative invertebral disc disease

Severe degenerative invertebral 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.

Mark Lutherborrow - Arrow-HCC Senior Research Scientist

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:

 

• The Unit devised gene-directed therapies to treat leukaemia and lymphoma.
• The Unit is investigating the exciting possibilities of producing new cells from adult stem cell to treat diseases such as arthritis, stroke and heart disease. Using bone marrow stem cells, the Unit has successfully taken the first steps to creating new human neural cells. This is an extension of research into bone marrow stem cell transplantation, an accepted treatment for life threatening blood diseases and cancer. The Unit recently completed a world-first blood stem cell transplant trials to treat severe Rheumatoid Arthritis.
• In keeping with its multi-disciplinary approach, the Unit collaborates with doctors and researchers in other medical specialties to determine genetic and environmental risk factors of thrombosis (blood clots).
• The Unit is using gene chip technology to simultaneously define the function of thousands of cellular genes in cancer patient samples. Research at the molecular level into how cancer cells respond to anti-cancer drugs will help the Unit invent better ways to treat cancers.
• The Unit relies on public donations, fundraising events and bequests in addition to competitive grants from government and non-government organizations, commerce, and the St Vincent's Healthcare Campus for funding.

Microsatellite DNA Project

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.

Gene Chip Project

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.

Future Work

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.