We currently have two funded projects:

Identification of Molecular Subtypes of Preeclampsia

Project held in collaboration with Dr. Shannon Bainbridge at the University of Ottawa

Funding Agency: CIHR

When placental development or function is compromised, poor maternal and foetal health outcomes follow. This situation occurs in 5-10% of all pregnancies, leading to the potentially life-threatening maternal complications of hypertension and kidney dysfunction known as preeclampsia. There is no cure for this disorder.

To begin to work towards treatment of these pathologies it is of tremendous importance to obtain a clear understanding of the pathological processes taking place in the placenta in order to generate effective treatments. Part of the difficulty in identifying and treating these disorders is the fact that clinically similar pathologies such as preeclampsia, can come in many different molecular forms. However, when a woman is diagnosed with preeclampsia we cannot tell what kind of preeclampsia she will have and therefore cannot predict what types of treatment will be effective in protecting the health of her and her unborn baby.

The purpose of this collaborative study is to specifically identify different subtypes of preeclampsia. This builds on Dr. Cox's previous work where he identified three different forms of preeclampsia and Dr. Bainbridge's work on biomarkers of preeclampsia. In this new project we are examining the placentas of a large cohort of women spanning the range of preeclampsia clinical presentation, to screen for differences in gene expression. We speculate that differences in some genes will be specific to the different kinds of preeclampsia. These differences will provide clues as to the diverse processes within the placenta that are directly involved in promoting the different preeclampsia subtypes. These genes, and the proteins they make, can be used as markers to help identify what type of preeclampsia a woman has and hopefully allow for tailored therapeutic treatments which will ultimately improve pregnancy outcomes.

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Placental Response to Heparin: Implications for the Prevention of Preeclampsia

Project held in collaboration with Dr. John Kingdom at Mount Sinai Hospital

Funding Agency: CIHR

Severe pre-eclampsia is a potentially serious form of hypertension, occurring in up to 5% women. The prevailing thought has been that this disease is caused by under vascularization and  numerous blood clots developing in the placenta, creating an environment starved of oxygen (hypoxic). Therefore it was thought that the use of anti-clotting agents, aspirin or heparin, could reduce the severity of the disease.

My collaborators group (Dr. John Kingdom) has shown that although there is some protective affect from heparin treatment on preeclampsia it is not due to anti-coagulant affects (Kingdom J. et al., JTH 2011).  Dr. Kingdoms group has observed that the culture of human placenta with heparin creates strong pro-angiogenic activity (Sobel, M, Kingdom J, Drewlo S, Obstet Gynecol 2011). His group also found that heparin did not decrease the expression of anti-angiogenic proteins such as sFlt1 (Drewlo S et al, JTH 2011). This is the "heparin-sFlt1 paradox" whereby heparin must prevent this disease independently of sFlt1 (Kingdom J and Drewlo S, BLOOD 2011).

Based on these exciting data together our groups propose that heparin interacts with the human placenta in a non-anti-coagulant manner to promote maternal vascular health to limit the development and severity of pre-eclampsia. Dr. Kingdom's group has developed a placenta culture system to enable the differential treatment of placentas with heparin and other agents. My group will apply molecular analysis of these cultures to characterize how heparin alters gene regulation. We are testing cell signalling and cell secretion pathways as potential targets of heparin.  We hope that our findings will aid in the development of non-anticoagulant heparin-like drugs that maximize disease prevention without incurring the potential maternal risks of anticoagulation during pregnancy.

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