A5089566049- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Mitochondrial Function and Pathology
- Genetics, Aging, and Longevity in Model Organisms
- Biotin and Related Studies
- Adipose Tissue and Metabolism
- Chromosomal and Genetic Variations
- Cancer-related gene regulation
- DNA Repair Mechanisms
- Histone Deacetylase Inhibitors Research
- Advanced Proteomics Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- Cancer, Hypoxia, and Metabolism
- Immunotherapy and Immune Responses
- CRISPR and Genetic Engineering
- Protein Degradation and Inhibitors
- Sperm and Testicular Function
- RNA Interference and Gene Delivery
- Genetics and Neurodevelopmental Disorders
- interferon and immune responses
- Genomics and Phylogenetic Studies
Ludwig-Maximilians-Universität München
2016-2025
Center for Integrated Protein Science Munich
2015-2025
Urologische Klinik München
2015-2018
Universität Bayern
2017
Munich Cluster for Systems Neurology
2014
Barcelona Biomedical Research Park
2013
Universitat Pompeu Fabra
2013
Institut d'Investigació Biomédica de Bellvitge
2013
Sine Institute
2013
Oryzon Genomics (Spain)
2009-2011
To study the longitudinal dynamics of anti-myelin oligodendrocyte glycoprotein (MOG) autoantibodies in childhood demyelinating diseases.We addressed kinetics anti-MOG immunoglobulins a prospective comprising 77 pediatric patients. This was supplemented by cross-sectional analyzing 126 patients with acute demyelination and 62 adult multiple sclerosis (MS). MOG-transfected cells were used for detection antibodies flow cytometry.Twenty-five children who immunoglobulin (Ig) positive at disease...
DNMT1 is recruited by PCNA and UHRF1 to maintain DNA methylation after replication. recognizes hemimethylated substrates via the SRA domain, but also repressive H3K9me3 histone marks with its TTD. With systematic mutagenesis functional assays, we could show that chromatin binding further involved PHD unmodified H3R2. These complementation assays clearly demonstrated ubiquitin ligase activity of RING domain required for maintenance methylation. Mass spectrometry UHRF1-deficient cells revealed...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evades most innate immune responses but may still be vulnerable to some. Here, we systematically analyze the impact of SARS-CoV-2 proteins on interferon (IFN) and autophagy. We show that synergize counteract anti-viral responses. For example, Nsp14 targets type I IFN receptor for lysosomal degradation, ORF3a prevents fusion autophagosomes lysosomes, ORF7a interferes with autophagosome acidification. Most activities are...
Common genetic variants in a conserved cis-regulatory element (CRE) at histone deacetylase (HDAC)9 are major risk factor for cardiovascular disease, including stroke and coronary artery disease. Given the consistency of this association its proinflammatory properties, we examined mechanisms whereby HDAC9 regulates vascular inflammation. bound mediated deacetylation NLRP3 NACHT LRR domains leading to inflammasome activation lytic cell death. Targeted deletion critical CRE mice increased Hdac9...
The circadian clock is constituted by a complex molecular network that integrates number of regulatory cues needed to maintain organismal homeostasis. To this effect, posttranslational modifications proteins modulate rhythms and are thought convert physiological signals into changes in protein function. explore reversible lysine acetylation dependent on the clock, we have characterized acetylome WT Clock -deficient ( −/− ) mouse liver quantitative mass spectrometry. Our analysis revealed...
Post-translational modifications of histones by chromatin modifying enzymes regulate structure and gene expression. As deregulation histone contributes to cancer progression, inhibition such as demethylases is an attractive therapeutic strategy impair growth. Lysine-specific demethylase 1 (LSD1) removes mono- dimethyl marks from lysine 4 or 9 H3. LSD1 in association with the androgen receptor (AR) controls androgen-dependent expression prostate tumor cell proliferation, thus highlighting a...
Article18 January 2016Open Access Transparent process Life span extension by targeting a link between metabolism and histone acetylation in Drosophila Shahaf Peleg Department of Physiological Chemistry, Biomedical Center for Integrated Protein Science Munich, Ludwig-Maximilians University, Planegg-Martinsried, Germany Molecular Biology, Search more papers this author Christian Feller Ignasi Forne Analysis Unit, Center, Evelyn Schiller Institute Experimental Genetics, Helmholtz Zentrum German...
The UCS (UNC-45/CRO1/She4) chaperones play an evolutionarily conserved role in promoting myosin-dependent processes, including cytokinesis, endocytosis, RNA transport, and muscle development. To investigate the protein machinery orchestrating myosin folding assembly, we performed a comprehensive analysis of Caenorhabditis elegans UNC-45. Our structural biochemical data demonstrate that UNC-45 forms linear chains offer multiple binding sites for cooperating client proteins. Accordingly, Hsp70...
Cells have evolved an elaborate DNA repair network to ensure complete and accurate replication. Defects in these machineries can fuel genome instability drive carcinogenesis while creating vulnerabilities that may be exploited therapy. Here, we use nascent chromatin capture (NCC) proteomics characterize the of replication-associated double-strand breaks (DSBs) triggered by topoisomerase 1 (TOP1) inhibitors. We reveal profound changes fork proteome, including environment nuclear membrane...
Apicomplexa are obligate intracellular parasites. While most species restricted to specific hosts and cell types, Toxoplasma gondii can invade every nucleated derived from warm-blooded animals. This broad host range suggests that this parasite recognize multiple ligands or structures, leading the activation of a central protein complex, which should be conserved in all apicomplexans. During invasion, unique secretory organelles (micronemes rhoptries) sequentially released several micronemal...
Abstract Pediatric high-grade gliomas (pHGG) are devastating and incurable brain tumors with recurrent mutations in histone H3.3. These promote oncogenesis by dysregulating gene expression through alterations of modifications. We identify aberrant DNA repair as an independent mechanism, which fosters genome instability H3.3 mutant pHGG, opens new therapeutic options. The two most frequent K27M G34R, drive replication-associated damage non-homologous end joining (NHEJ). Aberrant NHEJ is...
Chromatin states must be maintained during cell proliferation to uphold cellular identity and genome integrity. Inheritance of histone modifications is central in this process. However, the modification landscape challenged by incorporation new unmodified histones each cycle, principles governing heritability remain unclear. We take a quantitative computational modeling approach describe propagation H3K27 H3K36 methylation states. measure combinatorial patterns mass spectrometry on...
The S-adenosylhomocysteine (SAH) hydrolyzing enzyme AHCY functionally links the circadian clock to methionine metabolism.
Mitochondria contain their own gene expression systems, including membrane-bound ribosomes dedicated to synthesizing a few hydrophobic subunits of the oxidative phosphorylation (OXPHOS) complexes. We used proximity-dependent biotinylation technique, BioID, coupled with mass spectrometry delineate in baker’s yeast comprehensive network factors involved biogenesis mitochondrial encoded proteins. This (MiGENet) encompasses proteins transcription, RNA processing, translation, or protein...
Postzygotic isolation by genomic conflict is a major cause for the formation of species. Despite its importance, molecular mechanisms that result in lethality interspecies hybrids are still largely unclear. The genus Drosophila, which contains over 1600 different species, one best characterized model systems to study these questions. We showed past expression levels two hybrid incompatibility factors Hmr and Lhr diverged closely related Drosophila D. melanogaster simulans, resulting an...