Molecular cell biology and molecular pathology of the female reproductive tract
The laboratory works on cell interactions in implantation and placental development. We are interested in cell surface, adhesion to extracellular matrix and cell differentiation and the disturbances that occur in these processes in conditions ranging from infertility to pregnancy pathologies and neoplasia.
We think that understanding basic molecular processes will help to answer such big questions as:
- Why do so many pregnancies fail?
- Why is IVF inefficient?
- Why do some fetuses not grow enough?
- Why do women menstruate?
Implantation is critically important for life, yet is poorly understood! We believe that anti-adhesive mechanisms have to be overcome in order for the embryo successfully to implant. This appears to operate as a selection mechanism, preventing poor quality embryos from implanting.
Development of the placenta occurs rapidly after implantation, in fact the placenta is the first organ to form. Placental anatomy varies dramatically between species. In humans, the basic cellular organisation of the placenta is already present at about 32 days after the start of the last menstrual period, that is, usually before the mother knows she is pregnant! We have recently demonstrated that intricate IGF-dependent paracrine interactions govern placental development. Problems such as restricted fetal growth, pre-eclampsia and spontaneous miscarriage probably occur because basic cellular processes go awry during the early stages of pregnancy. Again, much more needs to be learned so that we can understand the origins of pregnancy pathology, and develop new treatments.
Projects include:
- MUC1 as an anti-adhesive glycoprotein at the cell surface of the endometrium and the blastocyst
- Glycans as markers of endometrial differentiation
- Anchoring villus morphogenesis
- Mechanisms that control trophoblast invasion.
- Vascular transformation in the placental bed
- Placental extracellular matrix
- The decidual extracellular matrix, MMPs and miscarriage (with Melissa Westwood, Manchester and Sergio Oliveira, Sao Paulo)
- IGFs and paracrine interactions at the maternofetal interface (with Melissa Westwood)
- Laminins in vulval and cervical carcinoma (with Henry Kitchener, Manchester)