The research work in my laboratory is focused on the cell biology of the ovary. Very specifically, three areas are investigated:
The impact of wnt signaling on follistatin
We were the first to demonstrate that wnt signaling (wnts) were involved in natal and adult murine ovaries. We have shown that wnt2 can affect gene expression in granulosa cells, specifically the peptide, follistatin. This peptide affects the activity of TGF-beta family members and therefore can affect follicle development and growth. We have found that activation of a wnt signal in the oocyte will identify follicles that cannot be ovulated. How or why this arises is not known and if it applies to primates, including humans, is unknown. Clearly, wnt signaling and its impact on follistatin are important in mammalian fertility regulation.
To determine the role of the wnt signaling pathway in:
1. Follicular development,
2. Granulosa cell differentiation and
3. Selection of follicles for ovulation.
Translational modulation in oocyte growth and maturation
We have shown that Clast-4 is a murine factor that binds specific mRNA and prevents them from being translated. Phosphorylation of Clast-4, however, releases the translational inhibition. Interestingly, phosphorylation of Clast-4 occurs in MII oocytes, which indicates that this aspect of gene expression is important. We have also found that Clast-4 probably functions as an mRNA transporter and is involved with storage of the transcript. We find it intriguing that a number of important molecules, such as E-cadherin, are regulated in the oocyte through translational modulation. Whether or not this involves Clast-4 is not known.
To determine if Clast-R plays a role in translational regulation of oocyte growth and maturation.
The role of wnts in specific ovarian cancer pathophysiology
More than 90% of ovarian cancer is derived from the ovarian surface epithelium (OSE). Our initial studies have identified wnt-2b, wnt-5 and wnt-11 expression in this tissue. Interestingly, the development of OSE in the embryo requires canonical wnt signaling, which diminishes as OSE develops. A very small proportion of OSE, in fact, show canonical wnt signaling. Interestingly, this small cell population shows some characteristics consistent with the notion of stem cells. We also examined the responses to wnt of a number of human ovarian cancer cell lines and find that they show different capabilities of wnt responses.
To assess the role of wnts in specific ovarian cancer pathophysiology.
Principal investigator: Dr Riaz Farookhi profile