A5073263131- Acute Myeloid Leukemia Research
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
- Immune Cell Function and Interaction
- Hematopoietic Stem Cell Transplantation
- Immune cells in cancer
- Cytokine Signaling Pathways and Interactions
- Protein Degradation and Inhibitors
- RNA Research and Splicing
- Wnt/β-catenin signaling in development and cancer
- Genomics and Chromatin Dynamics
- Chronic Myeloid Leukemia Treatments
- Multiple Myeloma Research and Treatments
- Histone Deacetylase Inhibitors Research
- Cancer Cells and Metastasis
- Mesenchymal stem cell research
- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- interferon and immune responses
- Corneal Surgery and Treatments
- Neuroinflammation and Neurodegeneration Mechanisms
- Connective tissue disorders research
- Corneal surgery and disorders
- DNA and Nucleic Acid Chemistry
- RNA Interference and Gene Delivery
Heidelberg University
2018-2024
University Hospital Heidelberg
2019-2024
Universität Hamburg
1999-2018
University Medical Center Hamburg-Eppendorf
2014-2018
University Cancer Center Hamburg
2018
Max Delbrück Center
2005-2014
Berlin-Brandenburger Centrum für Regenerative Therapien
2013
Charité - Universitätsmedizin Berlin
2013
Freie Universität Berlin
1993-2003
Cancer Research UK Manchester Institute
1999
Hematopoietic mutations in epigenetic regulators like DNA methyltransferase 3 alpha (DNMT3A), play a pivotal role driving clonal hematopoiesis of indeterminate potential (CHIP), and are associated with unfavorable outcomes patients suffering from heart failure (HF). However, the precise interactions between CHIP-mutated cells other cardiac cell types remain unknown. Here, we identify fibroblasts as partners monocytes. We used combined transcriptomic data derived peripheral blood mononuclear...
The estrogen receptor α (ERα) controls cell proliferation and tumorigenesis by recruiting various cofactors to response elements (EREs) control gene transcription. A deeper understanding of these transcriptional mechanisms may uncover therapeutic targets for ERα-dependent cancers. We show that BRD4 regulates ERα-induced expression affecting elongation-associated phosphorylation RNA polymerase II (RNAPII) histone H2B monoubiquitination. Consistently, activity is required ER+ breast...
Dendritic cells (DCs) are essential regulators of immune responses; however, transcriptional mechanisms that establish DC lineage commitment poorly defined. Here, we report the PU.1 transcription factor induces specific remodeling higher-order chromatin structure at interferon regulatory 8 (Irf8) gene to initiate fate choice. An Irf8 reporter mouse enabled us pinpoint an initial progenitor stage which DCs separate from other myeloid lineages in bone marrow. In absence Irf8, this undergoes...
Abstract Both fatty bone marrow (FBM) and somatic mutations in hematopoietic stem cells (HSCs), also termed clonal hematopoiesis (CH) accumulate with human aging. However it remains unclear whether FBM can modify the evolution of CH. To address this question, we herein present interaction between CH two preclinical male mouse models: after sub-lethal irradiation or castration. An adipogenesis inhibitor (PPARγ inhibitor) is used both models as a control. A significant increase self-renewal be...
The translocation (8;21), generating the AML1-ETO fusion protein, is one of most frequent chromosomal abnormalities associated with acute myelogenous leukemia (AML). To elucidate its role in oncogenesis, bone marrow (BM) cells were infected a retroviral vector carrying and transplanted into mice. In contrast to previous transgenic mouse models, we show that directly stimulates granulopoiesis, suppresses erythropoiesis, impairs maturation myeloid, B, T lymphoid vivo. determine significance...
Progression and disease relapse of chronic myeloid leukemia (CML) depends on leukemia-initiating cells (LIC) that resist treatment. Using mouse genetics a BCR-ABL model CML, we observed cross talk between Wnt/β-catenin signaling the interferon-regulatory factor 8 (Irf8). In normal hematopoiesis, activation β-catenin results in up-regulation Irf8, which turn limits oncogenic functions. Self-renewal myeloproliferation become dependent Irf8-deficient animals develop CML-like disease. Combined...
Although inhibitors of bromodomain and extra terminal domain (BET) proteins show promising clinical activity in different hematologic malignancies, a systematic analysis the consequences pharmacological BET inhibition on healthy hematopoietic (stem) cells is urgently needed. We found that JQ1 treatment decreases numbers pre-, immature mature B while early pro-B remain constant. In addition, increases apoptosis T cells, all together leading to reduced cellularity thymus, bone marrow spleen....
Abstract Hematopoietic mutations in epigenetic regulators like DNA methyltransferase 3 alpha (DNMT3A) drive clonal hematopoiesis of indeterminate potential (CHIP) and are associated with adverse prognosis patients heart failure (HF). The interactions between CHIP-mutated cells other cardiac cell types remain unknown. Here, we identify fibroblasts as interaction partners monocytes using combined transcriptomic data from peripheral blood mononuclear HF without CHIP the tissue. We demonstrate...
Abstract Microglia are established in embryogenesis forming a self-containing cellular compartment resisting seeding with cells derived from adult definitive hematopoiesis. We report that monocyte-derived macrophages (MoMΦ) accumulate the brain of aging mice distinct topology, including nigrostriatum and medulla, but not frontal cortex. Parenchymal MoMΦ adopt bona fide microglia expression profiles. Unlike microglia, these (MoMg) due to their hematopoietic origin targets clonal hematopoiesis...
The transcription factor C/EBPβ controls differentiation, proliferation, and functionality of many cell types, including innate immune cells. A detailed molecular understanding how directs alternative fates remains largely elusive. multitude signal-dependent post-translational modifications (PTMs) differentially affect the protean functions. In this study we apply an assay that converts primary mouse B lymphoid progenitors into myeloid cells in order to answer question regulates (trans-)...
The limbus of the eye is location corneal epithelial stem cell niche. These cells are necessary for continuous renewal epithelium. In case limbal deficiency, these damaged, and whole cornea becomes opaque. It important to be able identify that could applied new therapeutic strategies. There various known markers characterize cells, including p63, Nanog, oct4 FGFR2. However, none exclusively expressed in (they also transient amplified cells). seems likely a combination will identification....