A NESTED CASE CONTROL STUDY EVALUATING THE ASSOCIATION BETWEEN THE FACTOR V LEIDEN GENOTYPE AND ADVERSE PREGANCY OUTCOME
Funder
National Health and Medical Research Council
Funding Amount
$165,990.00
Summary
The factor V Leiden gene mutation is present in 1 in 20 of the general population. Recent studies suggest an association between the factor V Leiden gene mutation and adverse pregnancy outcomes. It is currently recommended that women with a history of recurrent pregnancy loss, including a second or third trimester intrauterine death should be screened for the factor V Leiden mutation. Controlled trials are currently underway assessing efficacy of treatment with anticoagulaton therapy for women w ....The factor V Leiden gene mutation is present in 1 in 20 of the general population. Recent studies suggest an association between the factor V Leiden gene mutation and adverse pregnancy outcomes. It is currently recommended that women with a history of recurrent pregnancy loss, including a second or third trimester intrauterine death should be screened for the factor V Leiden mutation. Controlled trials are currently underway assessing efficacy of treatment with anticoagulaton therapy for women who screen positive. However, population screening is currently not recommended because we do not know the significance of a factor V leiden gene mutation for women without a previous history of adverse pregnancy outcome. The question of why some women with a factor V Leiden mutation experience recurrent pregnancy loss whereas other women do not remains unanswered. The primary aim of this study is to determine whether the maternal and- or fetal genotype for factor V Leiden influences the risk of first and second trimester miscarriage within a cohort of 25,000 pregnant women. The aim of further research in this area is to identify a subset of women at increased risk of a second or third trimester fetal loss, based on a combination of genetic, acquired and environmental thrombophilic risk factors, who may benefit from prophylactic treatment with anticoagulation therapy.Read moreRead less
Endocrine Therapy Tolerance As A Cancer Cell Survival Mechanism For Late Recurring Breast Cancer
Funder
National Health and Medical Research Council
Funding Amount
$450,083.00
Summary
~25% of breast cancer deaths are attributable to cancers that have failed endocrine therapy and recur >5 years after primary diagnosis. These cancers are not well understood because their long latency makes them difficult to study. We have new models of this disease that identify a “therapy tolerant” population, and this is likely to re-emerge to cause late recurrence. Our work could potentially identify new biological tests and therapeutic strategies to treat late recurring breast cancer.
Control Of CD4 Function By Disulphide-Bond Switching
Funder
National Health and Medical Research Council
Funding Amount
$252,761.00
Summary
CD4 is a cell-surface protein that has two functions in the human body, a good one and a bad one. Its good function is as a checkpoint for development of the immune system and for response of the immune system to infection. It helps immune cells known as T cells to recognize and dispose of a foreign particle in the body. Its bad function is that it is one of two proteins that enable the HIV virus to enter and destroy immune cells. The HIV virus binds to CD4 on immune cells, which leads to fusion ....CD4 is a cell-surface protein that has two functions in the human body, a good one and a bad one. Its good function is as a checkpoint for development of the immune system and for response of the immune system to infection. It helps immune cells known as T cells to recognize and dispose of a foreign particle in the body. Its bad function is that it is one of two proteins that enable the HIV virus to enter and destroy immune cells. The HIV virus binds to CD4 on immune cells, which leads to fusion of the viral and immune cell surfaces and entry of the virus into the cell. Once inside the immune cell the virus reproduces itself and goes on to kill more immune cells. AIDS results when too many immune cells are killed. We have discovered that CD4 exists in three different forms on the immune cell surface; an oxidized, reduced or dimeric form. These different forms result from a molecular switch we discovered in CD4. We have suggested that the good and bad functions of CD4 are mediated by different forms of CD4. The good function is mediated by dimeric CD4, while the bad function is mediated by reduced CD4. The purpose of this application is to test this hypothesis. If we are correct then our findings will have significant implications for our understanding of how the immune system responds to a foreign invader and how HIV-AIDS destroys the immune system. This knowledge could be used to develop drugs that suppress the immune system when required, such as in organ transplantation, and that fight HIV-AIDS.Read moreRead less