The transforming growth factor beta (TGF-beta) superfamily is composed of a large group of growth and differentiation factors, including TGF-betas, activins, inhibins, Nodal, bone morphogenetic proteins (BMPs). These factors regulate a variety of cellular activities and are involved in many developmental and physiological processes. In recent years, we have been investigating the role of TGF- beta superfamily in female reproduction and the cellular and molecular mechanisms underlying their actions, as well as modulation of TGF-beta signalling by microRNAs.
Current research projects :
Regulation of zebrafish ovarian follicule development and oocyte maturation:
We have been studying the role of several TGF-beta members, such as activin-A, TGF-beta and BMP-15, on oocyte maturation. We are using various molecular and physiological approaches, including gene silencing, overexpression, microinjection, and immunoneutralization, to determine the physiological roles of these regulators during follicle development and oocyte maturation and the cellular and molecular mechanisms underlying their actions in the ovary. We are also investigating how their expression is regulated by microRNAs.
Role of cyclin G2 and microRNAs in ovarian cancer cells:
We have recently demonstrated that cyclin G2 is a target gene of Nodal, a member of the TGF-beta superfamily. Currently, we are investigating the role of cyclin G2 on ovarian tumorigenesis using in vivo and in vitro approaches. We are also determining how cyclin G2 expression is regulated by growth factors and microRNAs.
Nodal and its modulating microRNAs in Human Placenta:
We have shown that Nodal inhibits trophoblast cell proliferation, migration, and invasion but induces apoptosis. We have also found that Nodal is overexpressed, while several microRNAs potentially targeting Nodal are down regulated, in placentae obtained from pregnancies complicated by preeclampsia. We are determining how Nodal and its modulating microRNAs regulate placental development and how they may contribute to the pathogenesis of preeclampsia.
Our research has been supported by grants from Natural Science and Engineering research council, Canadian Institute of Health Research, Banting Research Foundation and J.P. Bickell Foundation and by Premier’s Research Excellent Award and Ontario Women’s Health Council/CIHR Mid-career Award.