Right now we have two main projects in the lab:

Mutant mice lacking estrogen receptor beta as a model for studying human ovulation and fertility. Infertility affects one in six Canadian couples, and in many cases is due to female infertility caused by infrequent or no ovulation. Ovulation, in which an egg is released from the ovary prior to fertilization, is a complex process which involves many tightly coordinated steps. Estrogen, which is produced by the ovary, plays a role in this process, although estrogen's role in ovulation is not well understood. Luteinizing hormone (LH) is released by the pituitary gland shortly after a sharp elevation in circulating levels of estrogen, triggering ovulation. The goal of this project is to determine the function of estrogen in LH-triggered ovulation using genetically altered mice in which the estrogen signaling system is disrupted. These mice lack the gene for estrogen receptor beta, which binds to estrogen and plays a poorly understood role in ovulation. The mutant mice provide an excellent model to study infertility because they have fewer offspring and ovulate less frequently than normal mice. Ovarian cells will be obtained from both normal and mutant mice, and will be grown in dishes and analyzed to determine how LH affects genes required for ovulation. By comparing the genes expressed in both mutant and normal ovary cells, the role that estrogen and estrogen receptor beta play in normal ovulation can be determined. Understanding how estrogen regulates ovulation may reveal causes of infertility in humans, and may result in new treatments for female infertility.

In breast tumours, in which estrogen is a mitogen and in which ERalpha and ERbeta are coexpressed, ERbeta is thought to protect against estrogen-stimulated proliferation driven through ERalpha. Understanding how ERbeta carries out this protective function may lead to development of novel pharmacological agents that enhance this protective effect.

Molecular function of the Thioredoxin/Thioredoxin Interacting Protein complex in the ovary. Our goal is to understand the role of the Thioredoxin/Thioredoxin Interacting Protein complex in the ovary. Thioredoxin (Txn) is a 12kD protein found in most prokaryotes and eukaryotes where it maintains cellular redox potential, protects cells against oxidative stress, and regulates transcription factor activity (1). Thioredoxin Interacting Protein (Txnip) binds Txn and inhibits Txn activity. Txnip is also widely expressed, and is found in species from nematodes to insects and vertebrates. Overexpression of Txnip inhibits cellular proliferation and increases apoptosis by inhibiting Txn function. Txnip is highly expressed in the mouse ovary and we are curious about its function!