Lab coats

The impact of Transposable Elements (TE)-derived activities on disease mechanisms

Project #2

Epigenetic disturbances in preeclampsia

Dr. Julia Rugor, PhD student Katarina Mitic (former Stevanovic), PhD Student Rabia Anwar

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.

We are aiming at discovering TE-affected gene regulation, TE-derived transcripts, and dysregulated miRNAs and their genes in PE. Our ultimate goal is to find diagnostic molecules that are released from the placenta into the blood stream, and could be established as biomarkers of PE.  

 

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.

 

Human endogenous retrovirus K in glioblastoma

Dr. Christine Römer

TLR8 is a human-specific intracellular receptor that recognizes single-stranded RNA, among others the human endogenous retrovirus K (HERV-K). We hypothesize that endogenously released endogenous retrovirus HERV-K functions as a ligand for the TLR8 in glioblastoma tumor tissue and aggravates tumor Progression.

 

Involvements of TEs in the human-specific nature of behavior and diseases

Manvendra Singh

Although each cell of a multicellular organism is a progeny of a single zygote, and shares the same genetic information with every other cell, cells differentiate to specialized forms such as nervous cells. Our research focuses on understanding the mechanistic basis by which covalent histone modifications over Transposed Elements (TEs) regulate gene expression patterns during the development of healthy and unhealthy cells. Transposable elements offer broad spectrum for key transcription factors to bind and regulate the expression of genes in their range. We integrate the vast array of genomic, epigenomes, transcriptomic (single cellular and bulk) and proteomic datasets from individuals showing the symptoms of Preeclampsia, Alzheimer, Schizophrenia and Reproductive dysfunctions.  Moreover, we look for aberrations in early development phases to see if a marker associated with symptoms can be detected earlier than the onset of disease. We add an evolutionary layer to our insights by comparing dynamics of host-genes and TEs in species-specific pattern.