A5043215484- Cancer-related Molecular Pathways
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Ion channel regulation and function
- Genomics and Chromatin Dynamics
- Cardiac electrophysiology and arrhythmias
- RNA Research and Splicing
- Cardiomyopathy and Myosin Studies
- Pluripotent Stem Cells Research
- Ubiquitin and proteasome pathways
- Ion Transport and Channel Regulation
- Cancer, Hypoxia, and Metabolism
- Orthopaedic implants and arthroplasty
- Tissue Engineering and Regenerative Medicine
- Orthopedic Infections and Treatments
- Hippo pathway signaling and YAP/TAZ
- CRISPR and Genetic Engineering
- Neuroscience and Neural Engineering
- Muscle activation and electromyography studies
- FOXO transcription factor regulation
- Total Knee Arthroplasty Outcomes
- Microtubule and mitosis dynamics
- Eosinophilic Disorders and Syndromes
- Nerve injury and regeneration
- Molecular Biology Techniques and Applications
Leibniz Institute on Aging - Fritz Lipmann Institute (FLI)
2018-2025
Medizinische Hochschule Hannover
2010-2024
Ludwig-Maximilians-Universität München
2023
LMU Klinikum
2023
Klinik und Poliklinik für Orthopädie, Physikalische Medizin und Rehabilitation
2023
Max Planck Institute of Molecular Cell Biology and Genetics
2022
Die Johanniter
2019-2021
Universität Ulm
2021
Goethe University Frankfurt
1968-2021
Dana-Farber Cancer Institute
2015-2019
The tumor suppressor p53 functions predominantly as a transcription factor by activating and downregulating gene expression, leading to cell cycle arrest or apoptosis. was shown indirectly repress of the CCNB2, KIF23 PLK4 genes through recently discovered p53-p21-DREAM-CDE/CHR pathway. However, it remained unclear whether this pathway is commonly used. Here, we identify regulated in genome-wide computational approach. bioinformatic analysis based on DREAM complex binding data, p53-depedent...
There are nearly 50 forkhead (FOX) transcription factors encoded in the human genome and, due to sharing a common DNA binding domain, they all thought bind similar sequences. It is therefore unclear how these targeted specific chromatin regions elicit biological effects. Here, we used immunoprecipitation followed by sequencing (ChIP-seq) investigate genome-wide mechanisms factor FOXM1. In keeping with its previous association cell cycle control, demonstrate that FOXM1 binds and regulates...
To harness the potential of human pluripotent stem cells (hPSCs), an abundant supply their progenies is required. Here, hPSC expansion as matrix-independent aggregates in suspension culture was combined with cardiomyogenic differentiation using chemical Wnt pathway modulators. A multiwell screen scaled up to stirred Erlenmeyer flasks and subsequently tank bioreactors, applying controlled feeding strategies (batch cyclic perfusion). Cardiomyogenesis sensitive GSK3 inhibitor CHIR99021...
Abstract Despite proven efficacy of pharmacotherapies targeting primarily global neurohormonal dysregulation, heart failure (HF) is a growing pandemic with increasing burden. Treatments mechanistically focusing at the cardiomyocyte level are lacking. MicroRNAs (miRNA) transcriptional regulators and essential drivers disease progression. We previously demonstrated that miR-132 both necessary sufficient to drive pathological cardiomyocytes growth, hallmark adverse cardiac remodelling....
Successful total knee arthroplasty is dependent on the correct alignment of implanted prostheses. Major clinical problems can be related to poor femoral component positioning, including sagittal plane and rotational malalignment. A prospective randomized study was designed test whether an optical navigation system for achieved greater implantation precision than a nonnavigated technique. The primary variable rotation in transverse plane, measured from postoperative radiographs computed...
The predominant function of the tumor suppressor p53 is transcriptional regulation. It generally accepted that p53-dependent activation occurs by binding to a specific recognition site in promoters target genes. Additionally, several models for repression have been postulated. Here, we evaluate these based on computational meta-analysis genome-wide data. Surprisingly, major gene regulation are implausible. Meta-analysis large-scale data unable confirm reports directly repressed genes and...
Significance Our study provided a comprehensive view of the transcriptional landscape across cell cycle. We revealed lag between transcription and steady-state RNA expression at cell-cycle level characterized large amount active during early mitosis. In addition, our analysis identified thousands enhancer RNAs related factors that are highly correlated with cell-cycle–regulated but not expression, thus highlighting importance epigenetic dynamics progression.
Abstract High risk human papilloma viruses cause several types of cancer. The HPV oncoproteins E6 and E7 are essential for oncogenic cell transformation. mediates the degradation tumor suppressor p53, can form complexes with retinoblastoma pRB suppressor. Recently, it has been shown that also interfere function DREAM transcriptional repressor complex. Disruption DREAM-dependent repression leads to untimely early expression central cycle regulators. p53-p21-DREAM pathway represents one...
Abstract Most human cancers acquire mutations causing defects in the p53 signaling pathway. The tumor suppressor becomes activated response to genotoxic stress and is essential for arresting cell cycle facilitate DNA repair or initiate apoptosis. p53-induced cycle-arrest mediated by expression of CDK inhibitor p21WAF1/Cip1, which prevents phosphorylation inactivation pocket proteins RB, p130, p107. In a hypophosphorylated state, bind E2F factors forming RB-E2F DREAM transcriptional repressor...
Aiming at clinical translation, robust directed differentiation of human pluripotent stem cells (hPSCs), preferentially in chemically defined conditions, is a key requirement. Here, feasibility suspension culture based hPSC-cardiomyocyte (hPSC-CM) production low-cost, xeno-free media compatible with good manufacturing practice standards shown. Applying stirred tank bioreactor systems increasing dimensions, our advanced protocol enables routine about 1 million hPSC-CMs/mL, yielding ∼1.3 × 108...
In recent years, our web-atlas at www.TargetGeneReg.org has enabled many researchers to uncover new biological insights and identify novel regulatory mechanisms that affect p53 the cell cycle - signaling pathways are frequently dysregulated in diseases like cancer. Here, we provide a substantial upgrade of database comprises an extension include non-coding genes transcription factors ΔNp63 RFX7. TargetGeneReg 2.0 combines gene expression profiling factor DNA binding data determine, for each...
Abstract Despite the biomedical importance of haematopoietic stem cells and progenitor cells, their in vitro stabilization a developmental context has not been achieved due to limited knowledge signals markers specifying multiple waves as well ethically restricted access human embryo. Thus, an approach resembling aspects development neighbouring tissues is interest. Our established pluripotent cell-derived heart-forming organoids (HFOs) recapitulate heart, vasculature foregut co-development....
Cell cycle-dependent gene expression is often controlled on the transcriptional level. Genes like cyclin B, CDC2 and CDC25C are regulated by cell element (CDE) cycle genes homology region (CHR) promoter elements mainly through repression in G 0 /G 1 . It had been suggested that E2F4 binding to CDE sites central regulation. However, some promoters only a CHR. We identify DREAM complex CHR of mouse human B2 Association regulation abrogated when mutated. Although E2f4 part complex, not...
Abstract Cell cycle gene expression occurs in two waves. The G1/S genes encode factors required for DNA synthesis and the G2/M contribute to mitosis. Retinoblastoma protein (RB) DREAM complex (DP, RB-like, E2F4 MuvB) cooperate repress all cell during G1 inhibit entry into cycle. damage activates p53 leading increased levels of p21 inhibition progression. Whether are differentially repressed by RB RB-like proteins p130 p107 response is not known. We performed profiling primary human...
Abstract The p53 transcription factor confers its potent tumor suppressor functions primarily through the regulation of a large network target genes. recent explosion next generation sequencing protocols has enabled study gene regulatory (GRN) and underlying mechanisms at an unprecedented depth scale, helping us to understand precisely how controls regulation. Here, we discuss our current understanding where binds DNA chromatin, pioneer-like role, this affects We provide overview GRN direct...