Epigentic regulation of trophoblats in severe preeclampsia

The human placenta is a transient organ of fundamental importance for a developing fetus. It fulfils duties that later in life are accomplished by many different organs, e.g. lungs, liver, kidneys and intestine. Main purposes of the placenta are nutrient and oxygen transfer from the mother to the fetus, waste disposal and the production of pregnancy hormones. To do so, the placenta attaches the uterus of the mother. Then, specialized placental cells named trophoblasts invade the uterus and adapt the micro-environment according the fetal requirements, which includes remodeling of blood vessels to increase the blood flow to the placenta. This delicate process was shown to be malfunctioning in preeclampsia, a pregnancy disorder that affects 1 in 20 pregnancies. The disease shows symptoms like high blood pressure and edema and can be life threatening for mother and fetus in severe cases. There are some therapeutic methods to milden the symptoms but the only cure is the delivery of the placentas, thus birth. Even though many studies have uncovered interesting and valuable information over the past decades, basic aspects of preeclampsia are still incompletely understood. The proposed project aims to investigate epigenetic changes of trophoblasts from cases of severe preeclampsia. This means in focus are modifications in the genetic material of these cells that influence their function but do not affect the sequence of the DNA. The laboratory of Professor Susan Fisher recently revealed that trophoblast cells in general exhibit unique epigenetic characteristics and their data suggest that these characteristics are altered in preeclampsia. The applicant therefore aims to perform a comprehensive and profound analysis with the team of Professor Susan Fisher at the University of California, San Francisco (UCSF), which is currently ranked 2nd among all medical schools worldwide in the Academic Ranking of World Universities. Finding and investigating epigenetic changes in detail in trophoblast cells in preeclampsia using state of the art sequencing techniques and bioinformatics at the UCSF can help to better understand the development of the disease and might contribute to find an effective treatment. The applicant currently works as a postdoc at the Medical University of Vienna on human trophoblast biology and already published several articles on that topic. Contributing in the outstanding team of Professor Susan Fisher definitely will advance the skills in molecular analysis with focus on trophoblast biology of the applicant and will significantly broaden the spectrum of methods he is able to use. Additionally, acquired knowledge and contacts would be of major advantage for the field of reproductive biology in Austria.