Research Areas

Ovarian Physiology

Our research has looked at mutations in a gene encoding a forkhead transcription factor, forkhead L2 (FOXL2), which, when mutated, leads to premature ovarian failure (POF) in patients with blepharophimosis, ptosis, and epicanthus inversus syndrome. We have conducted a number of studies on the localization and functional characterization of FOXL2. The Pisarska Laboratory has discovered that FOXL2 is sumoylated, leading to its regulation as a transcription factor. In addition, we discovered that a unique kinase, large tumor suppressor 1(LATS1), phosphorylates FOXL2 and also plays a role in its transcriptional regulation. Most recently, we discovered that FOXL2 can form a dimer as well as a heterodimer to the mutant FOXL2 protein that is associated with POF and this inhibits transcriptional regulation of wild-type FOXL2.

Our interest in FOXL2 has led to other areas of investigation. A specific point mutation in FOXL2 that leads to an amino acid substitution is present in granulosa cell tumors, a form of ovarian cancer. Our laboratory has already started investigating the functional activity of this particular mutation that leads to malignant transformation, with the ultimate goal of targeting the mutant protein for potential therapeutic purposes.

 

Molecular Determinants of Pregnancy Outcomes

We have already identified a number of genes that are differentially regulated in pregnancies conceived from couples with infertility compared to spontaneous conceptions. We have identified differences in a number of growth factors and transcription factors that may regulate early implantation, and we are currently studying their roles in early implantation.

We have also identified a number of factors that are alternatively regulated in the first trimester of pregnancies resulting in preterm labor and delivery. We have identified a number of inflammatory factors, cell adhesion molecules and, specifically in males, differences in genes associated with oxidation. We believe that these early changes lead to an altered intrauterine environment leading to premature labor and delivery.

 

Mutations in FOXL2 lead to premature follicle depletion and ovarian failure or granulosa cell tumors.

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