- Genomics and Chromatin Dynamics
- Viral-associated cancers and disorders
- Ubiquitin and proteasome pathways
- Single-cell and spatial transcriptomics
- Glycosylation and Glycoproteins Research
- Herpesvirus Infections and Treatments
- Acute Myeloid Leukemia Research
- RNA modifications and cancer
- RNA Research and Splicing
- Cytomegalovirus and herpesvirus research
- Cancer-related gene regulation
- Parvovirus B19 Infection Studies
- Polyomavirus and related diseases
- Circadian rhythm and melatonin
- Pain Management and Opioid Use
- Chronic Lymphocytic Leukemia Research
- Musculoskeletal pain and rehabilitation
- Nuclear Structure and Function
- Protein Degradation and Inhibitors
- Synthetic Organic Chemistry Methods
- Genetics and Neurodevelopmental Disorders
- Plant Molecular Biology Research
- Toxin Mechanisms and Immunotoxins
- Epigenetics and DNA Methylation
- Galectins and Cancer Biology
Karolinska University Hospital
2018-2022
Karolinska Institutet
2015-2022
Goethe University Frankfurt
2011-2015
Ludwig-Maximilians-Universität München
2014
Helmholtz Zentrum München
2010-2013
Epstein-Barr virus (EBV) causes a persistent infection in human B cells by establishing specific transcription programs to control cell activation and differentiation. Transcriptional reprogramming of EBV infected is predominantly driven the action nuclear antigens, among them transcriptional repressor EBNA3A. By comparing gene expression profiles wt EBNA3A negative cells, we have previously identified broad array cellular genes controlled We now find that repressed these are significantly...
Natural amino acid substitution by single-site nucleotide polymorphism can become a valuable tool for structure-activity correlations, especially if evidence association to disease parameters exists. Focusing on the F19Y change in human galectin-8, connected clinically rheumatoid arthritis, we here initiate study of consequences carbohydrate recognition domain this family cellular effectors. We apply strategically combined set structural and cell biological techniques comparing properties...
Abstract Abnormal WNT signaling increases MYC expression in colon cancer cells part via oncogenic super-enhancer-(OSE)-mediated gating of the active to nuclear pore a poorly understood process. We show here that principal tenet WNT-regulated gating, facilitating export mRNA, is regulated by CTCF binding site (CTCFBS) within OSE confer growth advantage HCT-116 cells. To achieve this, CTCFBS directs WNT-dependent trafficking from intra-nucleoplasmic positions stepwise manner. Once reaches...
Since Kaposi's sarcoma associated herpesvirus (KSHV) establishes a persistent infection in human B cells, cells are critical compartment for viral pathogenesis. RTA, the replication and transcription activator of KSHV, can either directly bind to DNA or use cellular binding factors including CBF1/CSL as adaptors. In addition, LANA1 vIRF4 known modulate RTA activity. To analyze contribution reactivation we have successfully infected DG75 knock-out cell lines with recombinant KSHV.219 selected...
In cells infected with the Kaposi's sarcoma-associated herpesvirus (KSHV), CSL/CBF1 signaling is essential for viral replication and promotes survival of KSHV-infected cells. a DNA adaptor molecule which recruits coactivator corepressor complexes to regulate cellular gene transcription major downstream effector activated Notch. The interaction KSHV RTA LANA has been shown balance lytic latent life cycle. Here we report that third protein, interferon regulatory factor 4 (vIRF4/K10), but none...
Chronic non-cancer pain (CNCP) is a common condition worldwide. The disease burden influenced not only by itself, but also psychiatric co-morbidities, which aggravate symptoms, generally negatively influence therapies, and may thereby lead to frustration, resignation, or withdrawal. A growing body of evidence suggests that sex gender aspects CNCP management as the experience pain, emotions associated with it, expression differ between women men. In addition, doctor-patient communication...
Abstract The relationship between stochastic transcriptional bursts and dynamic 3D chromatin states is not well understood. Using an innovated, ultra-sensitive technique, we address here enigmatic features underlying the communications MYC its enhancers in relation to process. thus interacts with flanking a mutually exclusive manner documenting that enhancer hubs impinging on detected large cell populations likely do exist single cells. Dynamic encounters pathologically activated responsive...
Abstract The relationship between stochastic transcriptional bursts and dynamic 3D chromatin states is not well understood due to poor sensitivity and/or resolution of current structure-based assays. Consequently, it established if enhancers operate individually in clusters coordinate gene transcription. In the study, we introduce Nodewalk, which uniquely combines high with enable analysis networks minute input material. >10,000-fold increase over other many-to-all competing methods...
The ALOX5 gene encodes 5-lipoxygenase (5-LO), a key enzyme of inflammatory reactions. 5-LO expression is induced by VitD3 and/or TGFβ and transcription initiation was associated with an increase in histone H3 lysine 4 trimethylation (H3K4me3) TSA-inducible fashion. Therefore, we investigated the effects MLL protein its derivatives, MLL-AF4 AF4-MLL, respectively. able to enhance promoter activity 47-fold which further stimulated when either VDR/RXR or SMAD3/SMAD4 were co-transfected....
Introduction: We have recently unraveled the composition of human AF4 and AF4-MLL protein complex by combining recombinant expression in cells with state-of-the art-biochemical mass spectrometry methods (Benedikt et al., 2011). Functional studies revealed functions both complexes. The is necessarily involved activation RNA polymerase II for transcriptional elongation. For this purpose, kinase activity associated P-TEFb certain histon methyltransferase activities are required. fusion merges...
We have recently established the composition and function of human AF4 AF4-MLL fusion protein complex (Benedikt et al., 2011). The is responsible for transcriptional elongation, while causing ectopic transcription, histone signatures was shown to induce proB ALL in a mouse model. both complexes has been eludidated by using affinity-purification from cells, nano LC-MS/MS analyses, Western blot co-IP experiments. Functional analysis performed different vitro vivo assays. Here, we will present...