Proprotein Convertase 6: A Master Regulator For The Development Of Endometrial Receptivity And Embryo Implantation
Funder
National Health and Medical Research Council
Funding Amount
$424,846.00
Summary
Implantation of an embryo into the womb (uterus) is a key step for human development, without which the embryo will only be able to develop to a very early stage the blastocyst stage (about 8 days after fertilization). For successful implantation, the uterus has to prepare itself to be receptive; this preparation is crucial as an ill-prepared uterus will reject the embryo. Such implantation failure is a major cause of early pregnancy loss and female infertility; ~30% of pregnancies end in sponta ....Implantation of an embryo into the womb (uterus) is a key step for human development, without which the embryo will only be able to develop to a very early stage the blastocyst stage (about 8 days after fertilization). For successful implantation, the uterus has to prepare itself to be receptive; this preparation is crucial as an ill-prepared uterus will reject the embryo. Such implantation failure is a major cause of early pregnancy loss and female infertility; ~30% of pregnancies end in spontaneous abortion. How the uterus becomes receptive is not well understood. Our recent research has identified that proprotein convertase 6 (PC6), an important master switch responsible for activating other proteins, is tightly regulated in the uterus during its preparation for receptivity and critical for implantation. This project will examine how PC6 acts in the human uterus to make it receptive, by identifying the factors that PC6 controls and how this controlling works. We will use a cell culture model with cells isolated from human term placenta. In addition, there is no means of readily testing whether the uterus is receptive owing to the lack of reliable biomarkers. In this study we will determine whether PC6 (and those molecules controlled by PC6) are potential biomarkers for uterine receptivity. This will be achieved by examining uterine biopsies and uterine washings collected from proven fertile volunteers and patients of proven endometrial infertility. This study will greatly enhance our understanding of how a critical molecule, PC6, acts in the uterus for implantation. The results will provide new knowledge regarding uterine preparation for implantation. The study has considerable implication for developing much-needed diagnostic and therapeutic tools for uterine receptivity and infertility.Read moreRead less
Chemoradiation And Adjuvant Chemotherapy Versus Radiation Alone In High Risk And Advanced Endometrial Cancer
Funder
National Health and Medical Research Council
Funding Amount
$460,832.00
Summary
This trial is evaluating whether adding chemotherapy during and after radiotherapy is better than giving radiotherapy alone in patients who have advanced or high risk endometrial cancer. One group of patients will be treated after surgery with both radiotherapy and chemotherapy, followed by additional cycles of chemotherapy and the other group will receive the standard treatment which is pelvic radiation alone. This study may result in a change in the management of these patients.
Critical Role Of Proprotein Convertase 6 In Human Uterine Epithelium For Embryo Implantation And Clinical Implications
Funder
National Health and Medical Research Council
Funding Amount
$643,899.00
Summary
Implantation of an embryo into the uterus is a key step for human development. Implantation failure causes embryonic death, pregnancy loss and infertility. Conversely, preventing implantation is an attractive approach for contraception. We have established that proprotein convertase 6 (PC6) is a master regulator of implantation. We will investigate how PC6 works in a woman's uterus, and how we can use this knowledge to improve implantation in IVF and to develop PC6 drugs for new contraceptives.
Progenitor Origin And Regulation In Endometrial Regeneration
Funder
National Health and Medical Research Council
Funding Amount
$847,583.00
Summary
The endometrium is the lining of the uterus and regenerates each month during a woman's reproductive years. Stem and progenitor cells in the endometrium are thought to be responsible for this regeneration. We have identified a genetic marker for stem and progenitor cells in the endometrium of mice and will use this to understand endometrial regeneration. This work will address infertility as well as overactive endometrial growth in diseases such as endometriosis and endometrial cancer.
Endometrial cancer (uterine or womb cancer) is the most common invasive gynaecological cancer in Australia. Each year more than 1400 women are affected by the condition, and death is common amongst a subset with more aggressive disease. We plan to conduct a national study of endometrial cancer to identify options for prevention of the disease. No previous studies have looked at risk factors for endometrial cancer in Australian women. In particular, we hope to identify modifiable risk factors for ....Endometrial cancer (uterine or womb cancer) is the most common invasive gynaecological cancer in Australia. Each year more than 1400 women are affected by the condition, and death is common amongst a subset with more aggressive disease. We plan to conduct a national study of endometrial cancer to identify options for prevention of the disease. No previous studies have looked at risk factors for endometrial cancer in Australian women. In particular, we hope to identify modifiable risk factors for endometrial cancer, and identify genes that make some women particularly susceptible to the disease. There are at least two main types of endometrial cancer and limited evidence suggests that they may have different causes. Few studies have examined the two different types separately, and there is virtually no information regarding risk factors for the more aggressive forms. In addition, little is known about genetic factors that predispose women to endometrial cancer. In the present study, we will investigate which genes cause endometrial cancer in women who have a strong family history of the disease. We will also identify genes that are related to endometrial cancer in women with no obvious family history of cancer, and investigate how these genes interact with environmental factors (such as hormone replacement therapy and obesity) to cause disease. National epidemiological studies of other cancers are currently being conducted by our research groups within QIMR. In the present proposal, we will use our experience to build on the infrastructure and procedures already in place to conduct a new study on endometrial cancer. As one of the largest population-based studies of endometrial cancer ever conducted, it will be able to answer many of the questions that are currently unresolved. Moreover, answers will be relevant to Australian women and clinicians as well as to inform prevention strategies.Read moreRead less
Mechanistic And Translational Studies In Female Reproductive Health
Funder
National Health and Medical Research Council
Funding Amount
$631,370.00
Summary
The womb is essential for a health pregnancy. This research aims to determine how the womb interacts with embryos to ensure a healthy pregnancy forms. Cells in the womb can also grow abnormally and result in endometrial cancer. New treatments for endometrial cancer will also be tested in this research.
I am a cancer epidemiologist, specialising in molecular epidemiology. I investigate the genetic and environmental causes of gynaecological cancers, and their consequences (prognosis, survival, quality of life, economic).