The following is an overview of current basic science research going on under the auspices of members of the Department of Obstetrics & Gynaecology at Western. If you are a graduate student looking for a niche, we strongly urge you to get in touch with the individuals cited.
The main focus of thelaboratory is investigating the role of nuclear receptors in fetal programming. While emerging epidemiological evidence suggests that the risks of adult onset diseases are inversely related to birth weight, very little is known about the genetic and/or epigenetic changes which underlie these alterations in fetal and postnatal development. Numerous animals models including maternal caloric and/or nutrient restriction, along with chemically induced gestational diabetes, hypoxia, LPS-invoked inflammation, glucocorticoid exposure, and decreased dietary protein have broadened our understanding how in utero insults may lead to restricted fetal growth. However, understanding the overall role of transcription factors involved in mediating these developmental abnormalities would provide us with better strategies in preventing the onset of adult diseases in mammals.
To address the molecular mechanisms underlying these ‘programmed' changes in nuclear receptor binding and downstream target genes, we employ chromatin immunoprecipitation (ChIP) in tissues and in cells to examine the in vivo binding of nuclear receptors to their respective promoters throughout fetal development. This helps us identify the crucial subset of lipid-sensing nuclear receptors underlying these fetal programming events. Moreover, the use of ChIP in vivo and in vitro further enhances our understanding of how epigenetic modifications are involved in the coordinated control of gene transcription during normal and abnormal fetal development.
The Pregnancy Research Group is led by Drs de Vrijer and Eastabrook with co-investigators Drs Victor Han, Peeyush Lala, Charles McKenzie, Debbie Penava, Timothy Regnault, Trevor Shepherd, and Samuel Siu. This team was awarded a Canadian Institutes of Health Research, Institute of Human Development, Child and Youth Health and Society of Obstetricians and Gynaecologists (CIHR/IHDCYH/SOGC) Team Grant of $746,764 for 5 years. Matching funds have been provided by the Children’s Health Research Institute/Children’s Health Foundation, the Dean's office, Department of Obstetrics and Gynaecology and Women’s Development Council.
The PRG has established collaborations to build upon actively operating and new pilot projects to develop larger multidisciplinary and prospective studies. Our goal is to become a centre of excellence not just for the clinical care of obese pregnancies, but also for research innovation in this rapidly growing and vulnerable population.
The PRG focuses on the development of novel tools and biomarkers to address difficulties in diagnosis and management of pregnancy complications in women with high BMI. The PRG also studies how the maternal environment (diet, obesity, chronic stress such as inflammation) affects the baby’s metabolism and which mechanisms lead to childhood obesity, insulin resistance and diabetes. The Paediatric component of our research focuses on the fetal development throughout its most vulnerable time, the first 1000 days of life, from conception to 2 years of age. Read more
This lab is currently looking at early environmental (during pregnancy) regulation of gene expression and organ development in the developing fetus asking the question, "How does early experience exert a sustained influence on postnatal metabolic function?"
Placental insufficiency and altered fetal nutrient supply is associated with reduced overall fetal development and growth, leading to Fetal Growth Restriction (FGR,) which represents approximately 5-7% of newborns. This altered growth comes about through a reprogramming of fetal physiology to maximize survivability in a sub-optimal in utero environment. There are now reports that these fetal alterations increase the likely hood for the development of insulin resistance and obesity in later life, as well as other associated diseases which are grouped together in the term Metabolic Syndrome.
Current research activities are in the following three areas:
Exciting research projects are currently available for Graduate students, Residents, and Honours students
Dr. Watson’s research investigates the mechanisms controlling development of the fertilized oocyte through the first week or preimplantation period of development, which prepares the early embryo for uterine implantation and initiation of pregnancy. He has supervised or co-supervised the research of 20 graduate students and currently supervises 3 graduate students.
His work is focused on understanding the earliest stages of development which includes the period from fertilization to implantation to the uterus and the beginnings of pregnancy. All of our studies use an animal model to investigate this early period of development. Results from animal studies can be translated to the human and help clinicians develop better ways of helping couples with fertility problems conceive and have their families. Research has demonstrated that the very beginning of development has a major impact on not only whether pregnancy will occur but also on the health of the fetus, newborn, child and even on susceptibility to disease in advanced life. Thus it is important to ensure that safe and efficient methods are applied in the clinic to ensure that the assistance provided to couples with fertility challenges not only allows them to start their family but also ensures that their family will enjoy the best health possible throughout their lifetime.
Dr. Yang has established an international collaboration with Professor Gang Sun at Fudan University, China, to investigate factors that contribute to premature delivery. They have recently secured funding from CIHR and Natural Science Foundation of China to support this joint research initiative. Dr. Yang has also initiated two new research projects: one examining how caffeine consumption during pregnancy may lead to low birth weight, and the other studying how BPA exposure during pregnancy may impact on fetal organ growth and maturation.
Dr. Yang has trained four postdoctoral fellows, all of whom are in senior academic positions. He has also trained numerous graduate, undergraduate, and summer students, with some of them taking up academic and management positions.