A5038123873- HIV Research and Treatment
- Lipid Membrane Structure and Behavior
- Viral Infections and Vectors
- Immune Cell Function and Interaction
- Protein Structure and Dynamics
- Fire effects on ecosystems
- T-cell and B-cell Immunology
- HIV/AIDS drug development and treatment
- Viral Infections and Outbreaks Research
- Mosquito-borne diseases and control
- Supramolecular Self-Assembly in Materials
- RNA Interference and Gene Delivery
- Influenza Virus Research Studies
- SARS-CoV-2 and COVID-19 Research
- CRISPR and Genetic Engineering
- CAR-T cell therapy research
- HIV-related health complications and treatments
- Cardiac electrophysiology and arrhythmias
- Animal Virus Infections Studies
- Photochromic and Fluorescence Chemistry
- Cytomegalovirus and herpesvirus research
- Molecular Sensors and Ion Detection
- Computational Drug Discovery Methods
- Virus-based gene therapy research
- Nanopore and Nanochannel Transport Studies
Essen University Hospital
2022-2025
Gladstone Institutes
2017-2024
University of Duisburg-Essen
2021-2024
Weizmann Institute of Science
2015-2022
University of California, San Francisco
2017-2021
Humboldt-Universität zu Berlin
2012-2020
Charité - Universitätsmedizin Berlin
2020
MSB Medical School Berlin
2020
Abstract Despite the success of combination antiretroviral therapy (ART) for individuals living with HIV, mild forms HIV-associated neurocognitive disorder (HAND) continue to occur. Brain microglia form principal target HIV infection in brain. It remains unknown how these cells leads neuroinflammation, neuronal dysfunction, and/or death observed HAND. Utilizing two different inducible pluripotent stem cell-derived brain organoid models (cerebral and choroid plexus [ChP] organoids) containing...
A new amphiphilic membrane marker based on a water-soluble dendritic polyglycerol perylene imido dialkylester has been designed, synthesized, and its optical properties characterized. In water it forms fluorescently quenched micellar self-aggregates, but when incorporated into lipophilic environment, monomerizes, the highly fluorescent of core are recovered. These make an ideal candidate for imaging artificial cellular membranes as demonstrated by biophysical studies.
The primary reservoir for HIV is within memory CD4+ T cells residing tissues, yet the features that make some of these more susceptible than others to infection by not well understood. Recent studies demonstrated CCR5-tropic HIV-1 efficiently enters tissue-derived expressing CD127, alpha chain IL7 receptor, but rarely completes replication cycle. We now demonstrate inability replicate in CD127-expressing due post-entry restriction SAMHD1. Rather, relative other cell subsets, are highly prone...
ABSTRACT One key determinant of HIV-1 latency reversal is the activation viral long terminal repeat (LTR) by cellular transcription factors such as NF-κB and AP-1. Interestingly, activity these two can be modulated glucocorticoid receptors (GRs). Furthermore, genome contains multiple binding sites for GRs. We therefore hypothesized that glucocorticoids other GR modulators may influence reactivation. To investigate how signaling affects latent reservoirs, we assembled a representative panel...
Enveloped viruses often use membrane lipid rafts to assemble and bud, augment infection spread efficiently. However, the molecular bases functional consequences of partitioning viral glycoproteins into microdomains remain intriguing questions in virus biology. Here, we measured Foerster resonance energy transfer by fluorescence lifetime imaging microscopy (FLIM-FRET) study role distinct proximal regions human immunodeficiency glycoprotein gp41 for raft living Chinese hamster ovary cells...
The family Hantaviridae comprises a diverse group of virus species and is considered an emerging global public health threat. Individual hantavirus differ considerably in terms their pathogenicity but also cell biology host-pathogen interactions. In this study, we focused on the most prevalent pathogenic Europe, Puumala (PUUV), investigated entry internalization PUUV into mammalian cells. We show that both clathrin-mediated endocytosis macropinocytosis are cellular pathways exploited by to...
An ability to activate latent HIV-1 expression could benefit many HIV cure strategies, but the first generation of latency reversing agents (LRAs) has proven disappointing. We evaluated AKT/mTOR activators as a potential new class LRAs. Two glycogen synthase kinase-3 inhibitors (GSK-3i's), SB-216763 and tideglusib (the latter already in phase II clinical trials) that signaling were tested. These GSK-3i's reactivated present blood samples from aviremic individuals on antiretroviral therapy...
Deciphering the mechanisms underlying viral persistence is critical to achieving a cure for human immunodeficiency virus (HIV) infection. Here, we implement systems approach discover molecular signatures of HIV latently infected CD4
HIV infects long-lived CD4 memory T cells, establishing a latent viral reservoir that necessitates lifelong antiretroviral therapy (ART). How this is formed so quickly after infection remains unclear. We now show the innate inflammatory response to results in CCL2 chemokine release, leading recruitment of cells expressing CCR2 receptor, including subset central cells. Supporting role for CCL2/CCR2 axis rapid formation, we find (i) treatment humanized mice with anti-CCL2 antibodies during...
While some chronic pathological substrates for sudden cardiac death (SCD) are well known (eg, coronary artery disease and left ventricular [LV] dysfunction), the acute vulnerable myocardial state predisposing to fatal arrhythmia remains a critical barrier near-term SCD prevention.
Abstract Hantavirus assembly and budding are governed by the surface glycoproteins Gn Gc. In this study, we investigated of Puumala, most abundant species in Europe, using fluorescently labeled wild-type constructs cytoplasmic tail (CT) mutants. We analyzed their intracellular distribution, co-localization oligomerization, applying comprehensive live, single-cell fluorescence techniques, including confocal microscopy, imaging flow cytometry, anisotropy Number&Brightness analysis....
Abstract This study presents a novel and easily applicable approach to recruit sulfhydryl‐containing biomolecules membranes by using palmitic acid which is functionalized with maleimide group. Notably, this strategy can also be employed preformed (biological) membranes. The applicability of the assay demonstrated characterizing binding Rhodamine‐labeled peptide lipid cellular methods fluorescence spectroscopy, lifetime measurement, microscopy. Our offers new possibilities for preparing...
Hantaviruses are enveloped viruses that possess a tri-segmented, negative-sense RNA genome. The viral S-segment encodes the multifunctional nucleocapsid protein (N), which is involved in genome packaging, intracellular transport, immunoregulation, and several other crucial processes during hantavirus infection. In this study, we generated fluorescently tagged N constructs derived from Puumalavirus (PUUV), dominant species Central, Northern, Eastern Europe. We comprehensively characterized...
Abstract The HIV-1 glycoprotein gp41 critically mediates CD4 + T-cell infection by during viral entry, assembly, and release. Although multiple immune-regulatory activities of have been reported, the underlying mechanisms these remain poorly understood. Here we employed multi-colour single molecule localization microscopy (SMLM) to resolve interactions proteins with cellular at plasma membrane (PM) fixed live T-cells resolution ~20–30 nm. We observed that clusters dynamically associated T...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can induce mild to life-threatening symptoms. Especially individuals over 60 years of age or with underlying comorbidities, including heart lung disease and diabetes, immunocompromised patients are at a higher risk. Fatal multiorgan damage in 2019 (COVID-19) be attributed an interleukin-6 (IL-6)-dominated cytokine storm. Consequently, IL-6 receptor (IL-6R) monoclonal antibody treatment for severe COVID-19 cases has been...
Viral glycoproteins are highly variable in their primary structure, but on the other hand feature a high functional conservation to fulfil versatile tasks during pathogenic life cycle. Typically, all protein domains optimized that indispensable functions can be assigned small conserved motifs or even individual amino acids. The cytoplasmic tail of many viral spike proteins, although particular relevance for virus biology, is often only insufficiently characterized. Hemagglutinin (HA),...