EPIC: Epigenetic (and genetic) studies of the Placenta in Complications of pregnancy (Preeclampsia, Intrauterine Growth Restriction, preterm birth):
Our lab is interested in understanding the role of genetic and epigenetic changes in the placenta in normal development and in pregnancies complicated by poor fetal growth, maternal preeclampsia (hypertension) and spontaneous preterm birth. We want to use this information to 1) understand the underlying causes of these outcomes 2) identify markers in maternal blood that can help predict which pregnancies will become complicated by these problems before symptoms are present 3) learn what the placenta can tell us about fetal well being and neonatal health. In particular, we are interested in pregnancies at risk of or diagnosed with preeclampsia, IUGR, or preterm birth.
‘Omics of the Placenta:
Through a grant funded by the NIH Human Placenta Project, we are investigating 1) ‘Omics profiles of placental cell types across gestation and by sex; 2) ‘Omics profiles of placenta in response to maternal stress. This is part of a cross Canada + Australia collaboration to develop improved understanding of some basic biology of the placenta and includes:
- DNA methylation (Illumina EPIC array)
- small RNA sequencing (miRNA and piRNA)
- ancestry informative marker typing
- serotonin and cytokine signalling
Sex and placental gene expression (CIHR funded):
Many differences between males and females originate before birth. Male and female fetuses differ in growth parameters, immune profile, neuroanatomy and risks for perinatal complications. As the primary organ regulating growth and development of the fetus, the placenta plays an important role in such differences. Placenta-specific escape from X-dosage compensation, is thought to lead to persistent higher expression of some X-linked genes in females. We have shown altered DNAme profiles in association with pregnancy complications, as well as changes on the autosomes related to sex. We are interested to study sex-differences in the placenta that impact fetal growth and development, and to consider that the influence of sex chromosome complement may be continuous, rather than dichotomous.
Mosaicism and chimerism:
We have long had an interest in errors that arise in the first few cell divisions leading to mosaic or chimeric placentas or fetuses. How do such errors arise? What factors (selection, chance, cell population sizes) influence where the different cell types end up in the body and what their effect will be on phenotype? How frequent are copy number changes in the placenta as compared to somatic tissues? Are these increased when placental pathology is present?
See also our Chromosome mosaicism web site.