Epigenetic disturbances in preeclampsia
PhD student Julia Rugor
In placenta, in comparison to other tissues, the genomic noise, generated by various TEs is relatively high. In collaboration with Prof. R. Dechend (Charité) and Prof. L. D. Hurst (University of Bath, UK) our aim is to investigate epigenetic regulation and imprinting abnormalities in the pathogenesis of preeclampsia, a pregnancy disorder associated with cardiovascular diseases of the mother. In collaboration with R. Dechend (Charité), we aim at establishing a SB transposon-based uteroplacental specific transgene expression model in pregnant rats, since as opposed to the mouse, rat placenta is relevant to humans.
Transcriptional activation of endogenous TEs in the human genome in response to a global epigenetic stress during induced pluripotency
Dr. Jichang Wang
Investigate the consequences of transcriptional activation of endogenous TEs in the human genome in response to a global epigenetic stress, specifically during induced pluripotency. While the endogenous TE promoters are intrinsically active in human cells, a relaxation in the control of their transcription is predicted in pluripotent stem cells, mediated by widespread epigenetic remodeling. As all known human mutagenic TE insertions are assumed to occur early in development, hESCs (human embryonic stem cells) were shown to model de novo transposition events in humans. Similarly, global epigenetic changes following induced pluripotency that resets the epigenetic status of the cells are expected to induce the transcription of certain TE families, including LINE-1 and various HERV families (W/E/R/K). We investigate the risk of genetic destabilization inflicted by upregulation of human endogenous TEs on the genome in pluripotent stem cell lines and their differentiated derivatives (Collaboration with Gerald Schumann, PEI, Germany.