I am a cell biologist investigating how cells in the developing testis communicate to set the stage for normal sperm production in the adult. My studies address what goes wrong in certain clinical conditions including testicular cancer, and our findings a
The Importance Of The Blood-testis Barrier In Human Infertility
Funder
National Health and Medical Research Council
Funding Amount
$560,953.00
Summary
The blood-testis barrier (BTB) shields developing sperm from the circulation and immune system, which would see them as ‘foreign’. Loss of BTB function leads directly to infertility. Curiously, how the BTB ‘opens’ and ‘closes’ to allow entry without causing a ‘leak’ is unknown. We believe that activin A is the main gatekeeper, but this growth factor is also important in inflammation. Our goals are to show how activin A allows sperm cells entry, and how inflammatory diseases impact the BTB.
Fibroblast Growth Factor Receptor 2c And Human Testicular Dysgenesis
Funder
National Health and Medical Research Council
Funding Amount
$611,197.00
Summary
Disorders of sex development (DSD) account for 7.5% of all birth defects. DSDs that affect testis development lead to testicular tumours, ambiguous genitalia, male-to-female sex reversal, and infertility. We have identified a novel protein (FGFR2) essential for testis development in mice and found the first FGFR2 mutations in DSD patients with testicular dysgenesis. Understanding the molecular action of FGFR2 will lead to improved diagnosis and management of DSD.
Male fertility requires sufficient production of healthy sperm in the testis. We discovered that cells in the adult testis communicate via the Hedgehog (Hh) signalling pathway as sperm develop. We propose to use a highly specific drug to inhibit Hh activity in order to delineate the precise steps in sperm production affected by Hh signalling. We will study the importance Hh in maintenance of spermatogonial stem cells and create mouse models to learn how it is controlled.
Germ Cell Development In The Postnatal Testis: The Key To Early Surgery To Prevent Infertility And Malignancy In Cryptorchidism
Funder
National Health and Medical Research Council
Funding Amount
$725,326.00
Summary
The germ cells have been studied very extensively before birth or after puberty, but little is known about what happens shortly after birth. In children with undescended testes, early germ cell development is deranged, and this may be the key to find the right time for surgery to prevent subsequent infertility and risk of cancer. This project proposes some novel hypotheses to explain this and the studies aim to obtain the evidence to support surgery in the first 3-6 months of life..
A man's reproductive health and fertility is affected by processes that occur long before adulthood. The testis and sperm precursor cells first form in the fetus and then grow until the time of puberty, when the upper limit for sperm production is set. This project studies how one key signaling molecule, activin, helps establish normal testicular architecture and drives maturation of sperm precursor cells, and how it contributes to aberrent function in men with testicular cancer.
Roles Of TGFbeta Receptor TGFBR3 (Betaglycan) In Testis Development
Funder
National Health and Medical Research Council
Funding Amount
$332,660.00
Summary
Diseases of the reproductive tract are major health issues. At lease 1 in 100 live births display some sort of gonadal defects. Later in adulthood, one in six couples are affected by infertility, and cancers of the reproductive tract which result in a significant number of deaths each year. This project focuses on understanding the role of the transformation growth factor beta receptor3 (Tgfbr3) in the embryonic and neonatal testis and its impact on adult male reproductive capacities and health.