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CD164: A Sialomucin Adhesion Molecule With Potent Growth Inhibitory Properties
Funder
National Health and Medical Research Council
Funding Amount
$242,545.00
Summary
Blood cell production in the adult mammal is normally restricted to the bone marrow. The ongoing production of blood cells is well regulated and dependent on the controlled proliferation and development of rare, multipotent precursors cells commonly termed stem cells. The blood forming stem cells exist in intimate contact with other cells and tissues that comprise the red bone marrow tissue. It is currently thought that stem cell localisation, survival and growth within the bone marrow is, in pa ....Blood cell production in the adult mammal is normally restricted to the bone marrow. The ongoing production of blood cells is well regulated and dependent on the controlled proliferation and development of rare, multipotent precursors cells commonly termed stem cells. The blood forming stem cells exist in intimate contact with other cells and tissues that comprise the red bone marrow tissue. It is currently thought that stem cell localisation, survival and growth within the bone marrow is, in part, regulated by specific interactions between the stem cells and neighbouring cells or the biochemical products of these cells. Stem cells use specific cell surface structures or cell adhesion molecules to mediate these important interactions. This project seeks to investigate the role in blood cell production, of a specific cell surface molecule, CD164, a member of a larger family of molecules with similar structural features thought to be involved in inhibition of cell growth. The main focus of the project is to identify a ligand or binding molecule for CD164. This information will allow an investigation of the consequences of binding between CD164 and its ligand by stem cells. It is proposed that the CD164-ligand interaction is one of a number of important inhibitory interactions used to regulate proliferation of stem cells. These studies will be greatly facilitated by the generation of a mouse lacking CD164.Read moreRead less
Understanding The Role Of B Cells In Gastric Cancer For The Design Of New Therapeutic Strategies
Funder
National Health and Medical Research Council
Funding Amount
$696,383.00
Summary
Gastric cancer is the 2nd most common cause of cancer-related death worldwide. Our laboratory has previously established clinically relevant mouse model of gastric cancers, and our preliminary results indicate a strong link between B cell tumor infiltration and gastric cancer progression. In this project, we aim to elucidate the role of B cells in gastric cancer and determine whether B-cell targeted therapy alone or in combination with chemotherapy can be beneficial against this malignancy.
Novel Signalling Pathways Leading To The Activation Of Glomerular Parietal Epithelial Cells
Funder
National Health and Medical Research Council
Funding Amount
$408,768.00
Summary
Chronic kidney disease (CKD) is a major health problem in Australia. CKD patients have very limited therapeutic options. The majority of diseases that lead to CKD are associated scarring of the renal filters. Parietal epithelial cells reside in these filters and play key roles in scarring development. However, the molecular mechanisms that lead to scarring in these renal filters remain unclear. This proposal aims to identify molecular pathways that may serve as future therapeutic targets.
Robotic Surgical System For Image Guided Non-invasive Focused Ultrasound Induced Ablation Of Liver Cancers
Funder
National Health and Medical Research Council
Funding Amount
$582,231.00
Summary
According to National Cancer Institute, liver and bile duct cancers are the fifth most common cancer in men and the seventh in women. Due to poor prognosis involving surgery, radiotherapy and chemotherapy, our aim is to develop a novel image-guided, radiation-free, non-invasive robotic HIFU system with means for compensation of organ movement during treatment. The objective is to produce damage to the target in a predictable and reproducible manner while sparing overlying surrounding tissues.
Clinical And Microbiological Predictors Of Post-operative Crohn's Disease Recurrence
Funder
National Health and Medical Research Council
Funding Amount
$120,253.00
Summary
The multi-centre randomised controlled POCER (Post-Operative Crohn’s Disease Recurrence) trial has shown that following “curative” surgery, the anti-tumour necrosis factor drug adalimumab prevents recurrent disease in almost all patients. I will examine the multiple factors that contribute to disease recurrence including assessment of mucosal microbiota, faecal biomarkers and serological antibody markers in patients with Crohn's disease. Results will improve clinical outcomes and change internat ....The multi-centre randomised controlled POCER (Post-Operative Crohn’s Disease Recurrence) trial has shown that following “curative” surgery, the anti-tumour necrosis factor drug adalimumab prevents recurrent disease in almost all patients. I will examine the multiple factors that contribute to disease recurrence including assessment of mucosal microbiota, faecal biomarkers and serological antibody markers in patients with Crohn's disease. Results will improve clinical outcomes and change international practice.Read moreRead less
Using Gene Delivery Tools To Understand And Treat Skeletal Muscle-related Disease
Funder
National Health and Medical Research Council
Funding Amount
$459,270.00
Summary
As a muscle biologist, I study the mechanisms that regulate skeletal muscle size, so that we can develop therapies for muscle wasting. What sets my research apart is my combination of expertise in muscle biology, and the use of recombinant viral vectors for altering the expression of specific genes exclusively in skeletal muscles. Our approaches enable us to study the inner workings of muscles in ways others cannot, and develop promising new therapies for treating muscle diseases.
Role Of The MicroRNA MiR144 In Haemopoiesis In Vivo
Funder
National Health and Medical Research Council
Funding Amount
$392,328.00
Summary
Recently a new form of gene regulation has been discovered involving small RNA molecules called microRNAs (miRNAs). Although vertebrates (like man, mouse and fish) contain many hundreds of miRNAs, the function and true gene targets of each individual miRNA are largely unknown. A better understanding the normal function and targets of miRNAs is needed so that their role in normal biology and disease development can be understood. These studies exploit the technical strengths of zebrafish, an mode ....Recently a new form of gene regulation has been discovered involving small RNA molecules called microRNAs (miRNAs). Although vertebrates (like man, mouse and fish) contain many hundreds of miRNAs, the function and true gene targets of each individual miRNA are largely unknown. A better understanding the normal function and targets of miRNAs is needed so that their role in normal biology and disease development can be understood. These studies exploit the technical strengths of zebrafish, an model of increasing importance in biomedical research, to study the function of a particular miRNA, miR144, and to identify its physiological target genes. Zebrafish have several advantages for studying miRNA function - several simple methods for experimentally altering miRNA levels are standard in zebrafish but not easy in other models like mice. miR144 has been chosen because it has an expression pattern that strongly suggests a role in blood development. Blood development and zebrafish technologies are central themes of the Lieschke laboratory. Preliminary experiments in zebrafish have shown that miR144 expression can be detected in blood cells, that it is functionally active when overexpressed, that its effect can be intercepted, and that there are blood-system effects of its misexpression, particularly in mutant zebrafish with abnormalities of blood development that provide a sensitized background for such studies. These studies will describe the expression of miR144 in detail in normal and abnormal zebrafish blood development. The effects of miR144 overexpression and knock-down of expression will be studied in detail. To identify the targets of mir144, a multifaceted microarray analysis will be performed, and the validity of candidate targets suggested by this will then be systematically tested. When finished, these studies will have characterised the physiology of this new blood regulator and identified the way it exerts its effect.Read moreRead less