A tale of 76,000 women
Tuesday, 12 October 2021, 1pm to 2pm
Preeclampsia is a complication of pregnancy that affects 3-5 % of women worldwide. It is one of the leading causes of maternal deaths and premature birth. It is diagnosed by elevated blood pressure (>140/90 mmHg), proteinuria and end-organ damage. The placenta is involved in this disease process though we are not entirely sure how. However, one newly emerging theory is the role of extracellular vesicles STB-EVs which are membrane-bound biomolecules that range between 30-1000 nm in size released by the placenta and detected in the circulation. STB-EVs have been reported to be higher in the circulation in PE compared to Normal. In addition, the phenotype of the STBEVs is believed to be different in PE compared to NP. However, it is unclear if the clinical manifestations attributable to STBEVs in PE is because more STBEVs are more abundant or because they are of a different phenotype or a combination of both. My work is hoping to build on the second premise.
My work explores the possibility that STBEV's as carriers of these soluble factors and primary propagators of the disease. I am working to tease out the mechanisms of Preeclampsia to identify, molecular targets which can serve as diagnostic, mechanistic or therapeutic targets with the use of multi-omics data analysis (transcriptomics, proteomics and integrated multi-omics). This will be the first study of its kind in the field.
Work so far
So far, I have isolated and characterised STBEV's from the placenta of 8 PE and 6 NP patients via ex-vivo placenta perfusion. We have performed and analysed mass spectrometry, coding RNA, and small RNA sequencing on STBEVs and their corresponding placenta lysate. This analysis represents in total 21 different subsets of analysis which have been able to identify a list of potential protein, mRNA and miRNA biomarkers and 2) a list of likely hub/critical proteins and mRNA, and 3) perturbed pathways as bioinformatically derived from the protein, mRNA and small RNA analysis and I have gone ahead to validate a few of these molecules. For my talk, I will focus on one of the -omics data
The potential implication of my research:
As devastating as PE can be, for a long time, we could only diagnose it by measuring the blood pressure and checking the protein in the urine and thus only detected the disease after it is well established with little time for an intervention. The introduction of sFLT/PLGF ratio, a metric of angiogenic balance as an add-on to the diagnostic test, considerably improved preeclampsia diagnosis. But the strength of sFLT/PLGF ratio is in its negative predictive value (NPV) and not its positive predictive value (PPV) that is it is mainly great at telling doctors which woman is unlikely to get PE and not which woman will get PE. In addition, we are still not clear about what to do to those women who are likely to get PE than to watch and wat. For my project, our fundamental assumption is that biological changes occur at the RNA level before being observed at the protein level. Thus, an mRNA/miRNA-based diagnostic test may help us identify/diagnose the disease much earlier in pregnancy when we have a chance of acting/treating this earlier. We would also bioinformatically identify potential target for drugs or other pharmacological agents, which may be a considerable step in PE therapeutics