Resistant forms of childhood acute lymphoblastic leukaemia (ALL) constitute a leading cause of cancer-related deaths in children. Despite tremendous improvements in therapy, 25-30% of patients still experience a relapse and many of them occur in patients stratified as low risk. Further treatment is often toxic, frequently unsuccessful and carries the risk of significant long-term morbidity. For the design of more appropriate therapy, information on the biology of relapsed ALL is urgently require ....Resistant forms of childhood acute lymphoblastic leukaemia (ALL) constitute a leading cause of cancer-related deaths in children. Despite tremendous improvements in therapy, 25-30% of patients still experience a relapse and many of them occur in patients stratified as low risk. Further treatment is often toxic, frequently unsuccessful and carries the risk of significant long-term morbidity. For the design of more appropriate therapy, information on the biology of relapsed ALL is urgently required. The sequencing of the human genome and advanced screening technology (microarrays) allow the detailed analysis of expression patterns in large numbers of specimens. We propose to study the genetic features of this disease by investigating 28 childhood ALL patients from whom we have stored specimens received at two time points, one at diagnosis and one at relapse. The hypothesis of this study is that relapsed leukaemias display genetic features which are correlated to their resistance to therapy. The specific questions we will be asking are: (1) Which genes are expressed at high levels in leukaemia specimens at the time of relapse while not expressed (or expressed at lower levels) at the time of diagnosis and vice versa? (2) What is the function of differentially expressed genes? (3) Is the pattern of gene expression correlated with resistance to the particular drug therapy used? (4) Is the leukaemia clone at relapse related or unrelated to the clone present at diagnosis, as determined by receptor rearrangement? The expression levels of identified discriminator genes will be confirmed by real-time quantitative polymerase chain reaction (PCR). The quality of this set of specimens makes them particularly suited to achieve the stated goals, providing a unique opportunity to investigate drug resistance in childhood ALL. The data generated will provide the basis for the examination of genes suitable as new therapeutic targets.Read moreRead less
Defining The Role Of The Major Subsets Of Renal Mononuclear Phogocytes
Funder
National Health and Medical Research Council
Funding Amount
$614,227.00
Summary
Chronic Kidney Disease (CKD) is a major cause of death and morbidity in Australia, and currently therapeutic options are limited. Renal mononuclear phagocytes (rMP) are important immune cells which play a central role in health and disease of the kidney. However, rMP are a heterogenous group of cells with a poorly defined role in the development and progression of CKD. We will define the role of major subsets of rMP in CKD, and explore their potential for treating CKD.
Translational Genomics And Combinatorial Drug Discovery To Improve Outcomes For Patients With Colorectal Cancer
Funder
National Health and Medical Research Council
Funding Amount
$640,210.00
Summary
Bowel cancer is a major public health burden in Australia. Over the next 5 years, A/Prof Sieber’s research will focus on understanding the molecular pathology of bowel cancer and how this determines the course of disease and response to therapy. Integrated genomic, functional and drug discovery studies will provide significant new insights into fundamental tumour biology and open up new avenues for diagnosis and treatment.
Creating An Empirically Based Classification System For Mental Illness
Funder
National Health and Medical Research Council
Funding Amount
$645,205.00
Summary
Mental disorders are typically diagnosed using a set of strictly agreed diagnostic criteria. For example, in the DSM-5 a major depression diagnosis requires at least five of nine symptom criteria to be met. However, the DSM-5 is now widely agreed to have important limitations for the work of researchers and clinicians. My research will overcome those limitations by completing a data-driven classification system based on the patterns in the ways people experience symptoms of mental illness.
A Dimensional-spectrum Model Of Mental Disorders: Developing New Assessments To Improve The Diagnostic Validity Of Multiple Mental Disorders
Funder
National Health and Medical Research Council
Funding Amount
$311,860.00
Summary
Advances in the scientific literature have highlighted that significant improvements to validity and clinical utility can be made through the use of a dimensional-spectrum model of psychopathology. To encourage the future use of the dimensional-spectrum model, the current research project aims to develop and test an innovative and novel assessment tool for diagnosing mental disorders in community and clinical populations using a dimensional-spectrum model as the guiding theoretical framework.
A Multi-site Randomised Controlled Trial Comparing The Severity Of Constipation Symptoms Experienced By Palliative Care Patients Receiving Usual Care Compared To Those Diagnosed And Managed According To The Underlying Pathophysiology.
Funder
National Health and Medical Research Council
Funding Amount
$498,795.00
Summary
This research aims to consider whether the problems of constipation in palliative care are less severe when the physical changes that underlie the problem are explored.
Life Threatening Cancer Across The Lifespan: Examining The Relevance Of Music To Patients And Their Companions
Funder
National Health and Medical Research Council
Funding Amount
$137,000.00
Summary
Although music is widely used, scant discussion about its therapeutic merit exists when compared to the spoken word. Throughout the Ages, ritualized music promoted health and loss adjustment, however, music is not pivotal in modern medicine. The research will examine people’s intuitive music usage when experiencing life threatening cancer and the relationship between music therapy participation and one’s later music experience. Findings will inform specific recommendations for music therapists a ....Although music is widely used, scant discussion about its therapeutic merit exists when compared to the spoken word. Throughout the Ages, ritualized music promoted health and loss adjustment, however, music is not pivotal in modern medicine. The research will examine people’s intuitive music usage when experiencing life threatening cancer and the relationship between music therapy participation and one’s later music experience. Findings will inform specific recommendations for music therapists and generic guidelines to extend music’s therapeutic effect in palliative care.Read moreRead less