Anogenital Human Papillomavirus Infection And Its Outcomes In Men
Funder
National Health and Medical Research Council
Funding Amount
$333,433.00
Summary
Anal human papillomavirus (HPV) infection is common in homosexual men. Low risk types cause anal warts and high risk types of HPV cause anal cancer. This study will determine incidence and risk factors for HPV infection in a cohort of young homosexual men, the association of anal warts treatment with HIV risk, and the specific association of HPV subtypes with anal cancer. The findings of this research will help delineate the potential benefits of HPV vaccination in this population.
A Phase 1b Trial Of Specific Immunotherapy For Recurrent Respiratory Papillomatosis
Funder
National Health and Medical Research Council
Funding Amount
$141,208.00
Summary
This project will determine whether immunisation can be used to effectively treat an existing infection. To date, immunisation has only been used to prevent infection, but there are many chronic infections where intervention might help the body's defences to to a better job and clear the chronic infection. In this study, we will work out whether this approach can be applied to a virus infection ( papillomavirus) which is associated with cancer. We will test immunisation against a chronic and lif ....This project will determine whether immunisation can be used to effectively treat an existing infection. To date, immunisation has only been used to prevent infection, but there are many chronic infections where intervention might help the body's defences to to a better job and clear the chronic infection. In this study, we will work out whether this approach can be applied to a virus infection ( papillomavirus) which is associated with cancer. We will test immunisation against a chronic and lifethreatening disorder in which warts grow in the respirarory tract, as there is currently no satisfactory treatment for this. If the project is successful we may also learn which blood tests are likely to predict the outcome of immunisation to treat infection.Read moreRead less
HPV And Cervical Carcinoma: Signaling And Clinical Responses To Interferons
Funder
National Health and Medical Research Council
Funding Amount
$534,480.00
Summary
Cervical carcinoma and its treatment continues to be an important health concern in Australia. The interferons comprise an elaborate system of natural substances produced in the body, one of whose functions is to prevent cancer cells from developing. The interferons have been widely used to treat human diseases including viral infections and cancers caused by the wart virus. However, results of recent work indicates that viruses like the wart virus, HPV, have developed ways of inhibiting its eff ....Cervical carcinoma and its treatment continues to be an important health concern in Australia. The interferons comprise an elaborate system of natural substances produced in the body, one of whose functions is to prevent cancer cells from developing. The interferons have been widely used to treat human diseases including viral infections and cancers caused by the wart virus. However, results of recent work indicates that viruses like the wart virus, HPV, have developed ways of inhibiting its effectiveness. We have found that cervical carcinoma cells and virally infected cells resist the direct anti-cancer and anti-viral effects of interferons because they have abnormalities in their ability to respond to interferon. We have made good progress in understanding why these cells do not respond to the interferons. In particular they show a deficiency in the activity of cell proteins required to transmit the interferon signal inside the cells. The current proposal will allow us to gain a greater understanding of the processes inside cells that are taken over by the wart viral proteins and the reasons for its abnormality in interferon resistant cancer cells. We will determine whether the levels of certain genes in clinical samples from patients relates to their response to interferon treatment. This may allow us to establish a test to predict which patients will respond to interferon therapy, saving patients from ineffective treatment, side effects and cost. This study will have a broad significance to many human diseases where abnormalities in interferon signaling occur and will help to bring about the necessary changes in cell properties to overcome the abnormalities, restore the responses and improve the application of interferons to treat infectious diseases and perhaps other cancers as well.Read moreRead less
The Role Of Suppressor Of Cytokine Signalling-3 (SOCS-3) In Chondrocytes During Development And Disease
Funder
National Health and Medical Research Council
Funding Amount
$348,392.00
Summary
Cytokines are messenger proteins produced and secreted from one cell which then bind to specific receptors on the surface of other cells. After binding, a series of intracellular events occurs, termed signalling, that results in the target cell changing its behaviour. Cytokine signalling, if allowed to proceed unchecked, can result in various disease states. The suppressor of cytokine signalling (SOCS) proteins are key negative regulators of cytokine signalling within the cell. They are induced ....Cytokines are messenger proteins produced and secreted from one cell which then bind to specific receptors on the surface of other cells. After binding, a series of intracellular events occurs, termed signalling, that results in the target cell changing its behaviour. Cytokine signalling, if allowed to proceed unchecked, can result in various disease states. The suppressor of cytokine signalling (SOCS) proteins are key negative regulators of cytokine signalling within the cell. They are induced by a wide range of stimuli, especially from a group called the IL-6 family. We have preliminary data showing that cartilage cells (chondrocytes) normally produce a particular SOCS protein, called SOCS-3. We have also shown that when SOCS-3 production is dysregulated, the chondrocytes undergo excessive proliferation. Normal chondrocyte function is important during skeletal development and diseases such as osteoarthritis are thought to result from abnormal chondrocyte behaviour. It is likely that SOCS-3 has a key role in regulating chondrocyte function. The aim of this proposal is therefore to examine the role of SOCS-3 in chondrocytes, during development and in disease. Much of our understanding of the role of the SOCS proteins comes from the construction of mutant mice that lack a particular SOCS protein. When mutant mice are made that lack SOCS-3 in the whole animal the mice die before birth and so virtually nothing is known about the role of SOCS-3 in chondrocytes and the implications for cartilage in disease states, such as arthritis. To answer this we will create mice that lack SOCS-3 specifically in their chondrocytes. Evaluating the role of SOCS-3 in cartilage development and chondrocyte function during degenerative and inflammatory disease states is potentially of major clinical importance in improving our understanding of arthritis and of cartilage repair.Read moreRead less
Defining The Role Of GILZ In Inflammatory Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$675,030.00
Summary
Corticosteroids are commonly used to treat inflammatory diseases such as arthritis. Their action is based on effects on natural inflammation control pathways. One such pathway is that mediated by the protein known as GILZ (glucocorticoid induced leucine zipper). The function of this protein in disease is not well understood, and the research proposed here will increase understanding of its role. This knowledge could yield new treatments for arthritis and other inflammatory diseases.
The Role Of Post-translationally Modified Antigen In Rheumatoid Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$609,535.00
Summary
Rheumatoid arthritis (RA) is an inflammatory disease of joints. People who get RA often develop antibodies which react against proteins found in inflamed joints. We will investigate why cells of the immune system react against these proteins in RA, and identify which joint proteins, especially abnormal proteins, are targeted. This will allow us to design new approaches to treat RA in a way that just targets the response to these abnormal proteins, rather than the entire immune system.
The Role Of The Plasminogen Activators (PAs), Urokinase-PA And Tissue-type PA In Arthritis
Funder
National Health and Medical Research Council
Funding Amount
$481,500.00
Summary
Many diseases, such as rheumatoid arthritis (RA), are inflammatory by nature. Intra-articular fibrin deposition is an early and persistent hallmark of inflammatory responses, resulting from an altered balance between coagulation (the production of fibrin) and fibrinolysis (the breakdown of fibrin). This fibrin accumulation can have adverse effects in RA, including mediating and-or enhancing inflammation, and contributing to subsequent joint damage. The plasminogen activators (PA), urokinase PA ( ....Many diseases, such as rheumatoid arthritis (RA), are inflammatory by nature. Intra-articular fibrin deposition is an early and persistent hallmark of inflammatory responses, resulting from an altered balance between coagulation (the production of fibrin) and fibrinolysis (the breakdown of fibrin). This fibrin accumulation can have adverse effects in RA, including mediating and-or enhancing inflammation, and contributing to subsequent joint damage. The plasminogen activators (PA), urokinase PA (u-PA) and tissue-type PA (t-PA) convert plasminogen into plasmin which can then breakdown the accumulated fibrin. Their presence in RA patients would therefore be beneficial. However, u-PA is also implicated in cell migration leading to inflammatory cells accumulating in the joint, and cartilage destruction, both of which are detrimental to disease outcome. In the joints of RA patients there are high levels of u-PA and low levels of t-PA. We, and our collaborators, have found that in the absence of t-PA, disease is exacerbated, whilst in the absence of u-PA, the outcome depends on the type of disease, either exacerbating or ameliorating disease. This highlights the different roles u-PA can have. The current proposal aims to determine the role of u-PA in inflammation and arthritis, and whether enhancing t-PA can have beneficial outcomes with respect to disease severity. In addition, we will also study whether intra-articular fibrin deposition can, in fact, drive the inflammatory reaction and cartilage destruction seen in RA. The findings will be important for our understanding of the role of fibrin accumulation in the inflammatory and destructive processes that occur in RA, and the roles of u-PA and t-PA in enhancing and preventing them respectively. Information gained will provide clues for useful strategies for the treatment of human inflammatory diseases, including RA.Read moreRead less
Using cutting edge sequencing and genotyping technology, genes causing common and rare human diseases will be identified, and genetic methods developed to diagnose genetic diseases in both antenatal and postnatal life. Treatments for common rheumatic diseases affecting tens of thousands of Australians will be developed informed by these genetic findings.