A5026318125- Single-cell and spatial transcriptomics
- Poxvirus research and outbreaks
- Herpesvirus Infections and Treatments
- Neuroscience and Neuropharmacology Research
- RNA and protein synthesis mechanisms
- Neurogenetic and Muscular Disorders Research
- CRISPR and Genetic Engineering
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA modifications and cancer
- Virus-based gene therapy research
- Cell death mechanisms and regulation
- RNA Interference and Gene Delivery
- RNA Research and Splicing
- Immunotherapy and Immune Responses
- Apelin-related biomedical research
- Receptor Mechanisms and Signaling
- Epigenetics and DNA Methylation
- Anesthesia and Neurotoxicity Research
- Inflammation biomarkers and pathways
- Pluripotent Stem Cells Research
- Muscle Physiology and Disorders
- Extracellular vesicles in disease
- Effects of Radiation Exposure
- Memory, violence, and history
- Colorectal Cancer Screening and Detection
Novartis (Switzerland)
2004-2023
Novartis Institutes for BioMedical Research
2004-2022
University of Alabama at Birmingham
2020
University of Virginia Health System
2019
University of Virginia
2019
CEA Grenoble
2018
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2018
Oregon Health & Science University
2013
Imperial College London
2002-2012
University of Neuchâtel
2002
The evolutionary relationships of 26 sequenced members the poxvirus family have been investigated by comparing their genome organization and gene content using DNA protein sequences for phylogenetic analyses. central region chordopoxviruses (ChPVs) is highly conserved in arrangement, except some inversions Fowlpox virus (FPV) species-specific insertions FPV Molluscum contagiosum (MCV). In 90 genes are all ChPVs, but no from near termini throughout subfamily. Inclusion two entomopoxvirus...
Here we report Digital RNA with pertUrbation of Genes (DRUG-seq), a high-throughput platform for drug discovery. Pharmaceutical discovery relies on screening, yet current platforms have limited readouts. RNA-seq is powerful tool to investigate effects using transcriptome changes as proxy, standard library construction costly. DRUG-seq captures transcriptional detected in at 1/100th the cost. In proof-of-concept experiments profiling 433 compounds across 8 doses, transcription profiles...
Huntington's Disease (HD) is a progressive neurodegenerative disorder caused by CAG trinucleotide repeat expansions in exon 1 of the huntingtin (HTT) gene. The mutant HTT (mHTT) protein causes neuronal dysfunction, causing motor, cognitive and behavioral abnormalities. Current treatments for HD only alleviate symptoms, but cerebral spinal fluid (CSF) or central nervous system (CNS) delivery antisense oligonucleotides (ASOs) virus vectors expressing RNA-induced silencing (RNAi) moieties...
Camelpox virus (CMPV) and variola (VAR) are orthopoxviruses (OPVs) that share several biological features cause high mortality morbidity in their single host species. The sequence of a virulent CMPV strain was determined; it is 202182 bp long, with inverted terminal repeats (ITRs) 6045 has 206 predicted open reading frames (ORFs). As for other poxviruses, the genes tightly packed little non-coding sequence. Most within 25 kb each terminus transcribed outwards towards terminus, whereas centre...
A new apoptosis inhibitor is described from vaccinia virus, camelpox and eukaryotic cells. The a hydrophobic, multiple transmembrane protein that resident in the Golgi named GAAP (Golgi anti-apoptotic protein). Stable expression of both viral (v-GAAP) human (h-GAAP), which expressed all tissues tested, inhibited induced by intrinsic extrinsic apoptotic stimuli. Conversely, knockout h-GAAP siRNA cell death apoptosis. v-GAAP display overlapping functions as shown ability to complement for loss...
TREM2 is a transmembrane protein expressed exclusively in microglia the brain that regulates inflammatory responses to pathological conditions. Proteolytic cleavage of membrane affects microglial function and associated with Alzheimer's disease, but consequence reduced proteolytic has not been determined. Here, we generate transgenic mouse model Trem2 shedding (Trem2-Ile-Pro-Asp [IPD]) through amino-acid substitution an ADAM-protease recognition site. We show Trem2-IPD mice display increased...
We develop CellSIUS (Cell Subtype Identification from Upregulated gene Sets) to fill a methodology gap for rare cell population identification scRNA-seq data. outperforms existing algorithms specificity and selectivity types their transcriptomic signature in synthetic complex biological Characterization of human pluripotent differentiation protocol recapitulating deep-layer corticogenesis using reveals unrecognized complexity stem cell-derived cellular populations. enables novel populations...
Golgi antiapoptotic protein (GAAP) is a novel regulator of cell death that highly conserved in eukaryotes and present some poxviruses, but its molecular mechanism unknown. Given alterations intracellular Ca(2+) homeostasis play an important role determining sensitivity to apoptosis, we investigated if GAAP affected signaling. Overexpression human (h)-GAAP suppressed staurosporine-induced, capacitative influx from the extracellular space. In addition, it reduced histamine-induced release...
Macrophages are key cell types of the innate immune system regulating host defense, inflammation, tissue homeostasis and cancer. Within this functional spectrum diverse often opposing phenotypes displayed which dictated by environmental clues depend on highly plastic transcriptional programs. Among these 'classical' (M1) 'alternative' (M2) macrophage polarization best characterized. Understanding in humans may reveal novel therapeutic intervention possibilities for chronic wound healing...
Unbiased transcriptomic RNA-seq data has provided deep insights into biological processes. However, its impact in drug discovery been narrow given high costs and low throughput. Proof-of-concept studies with Digital RNA pertUrbation of Genes (DRUG)-seq demonstrated the potential to address this gap. We extended DRUG-seq platform by subjecting it rigorous testing adding an open-source analysis pipeline. The results demonstrate reproducibility ability resolve mechanism(s) action for a diverse...
Crude extracts of 57 species European fungi have been tested for their bactericidal (Bacillus subtilis, Escherichia coli), fungicidal (Candida albicans, Cladosporium cucumerinum), larvicidal (Aedes aegypti), molluscicidal (Biomphalaria glabrata), antioxidant and free-radical scavenging activities. Connatine 2(3,4-dihydroxyphenyl)glycine, two compounds with properties, were subsequently isolated from the methanolic Lyophyllum connatum (Tricholomataceae) Cortinarius hercynicus...
Corticotropin-releasing factor (CRF) is known to play an important role in the body response stress. Butyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-ethylamine (CP-154,526) a CRF(1) antagonist showing anxiolytic activities rats behavioral models, suggesting that CP-154,526 crosses blood-brain barrier. However, there no direct evidence for this. This study determined pharmacokinetic profile of after i.v. and p.o. application. After bolus, concentration declined...
Camelpox virus (CMLV) gene 176R encodes a protein with sequence similarity to murine schlafen (m-slfn) proteins. In vivo , short and long members of the m-slfn family inhibited T-cell development, whereas in vitro only m-slfns caused arrest fibroblast growth. CMLV 176 (v-slfn) is most closely related m-slfns; however, when expressed stably mammalian cells, v-slfn did not inhibit cell predominantly cytoplasmic 57 kDa that throughout infection. Several other orthopoxviruses encode proteins,...
Although Vaccinia virus (VACV) was used to eradicate smallpox by dermal vaccination, there is little information available about the immune response induced at vaccination site. Previously, an intradermal murine model that mimics established. Here, this investigate which leukocytes are recruited infected lesion and what kinetics of recruitment. Data presented show VACV infection infiltration macrophages, followed granulocytes lymphocytes. Up 4 days post-infection, major lymphocyte population...
Abstract Resident adult epithelial stem cells maintain tissue homeostasis by balancing self-renewal and differentiation. The cell potential of human epidermal keratinocytes is retained in vitro but lost over time suggesting extrinsic intrinsic regulation. Transcription factor-controlled regulatory circuitries govern identity, are sufficient to induce pluripotency transdifferentiate cells. We investigate whether transcriptional circuitry also governs phenotypic changes within a given type...
Recent advances in combining flow cytometry and mass spectrometry have led to the development of cytometry, allowing for interrogation complex cell populations on an unprecedented scale. The volumes high dimensionality data pose significant challenges terms analysis visualization. We implement a method called Radviz, where multidimensional single can be visualized as projection that maintains original dimensions complexity whilst facilitating This enables identification changes populations,...
Previous studies suggest that rapid eye movement sleep rebound and disruption of architecture occur during the first 24 h after general anesthesia with volatile anesthetics in adult rats. However, it is unknown whether alterations persist beyond anesthetic recovery phase neonatal This study tested hypothesis disturbances would be present adolescent rats treated on postnatal day 7.Forty-four were randomly allocated to treatment consisting midazolam, nitrous oxide, isoflurane or control...
Oral and intestinal mucositis is a debilitating side effect of radiation treatment. A mouse model radiation-induced leads to weight loss tissue damage, reflecting the human ailment as it responds keratinocyte growth factor (KGF), standard-of-care Cultured crypt organoids allowed development an assay monitoring treatments epithelium damage. This in vitro resembles KGF roof plate-specific spondin-1 (RSPO1) enhanced organoid recovery following radiation. Screening identified compounds that...
The multilineage differentiation capacity of mouse and human embryonic stem (ES) cells offers a testing platform for small molecules that mediate mammalian lineage determination cellular specialization. Here we report the identification two which drives 129 ES cell to skeletal muscle with high efficiency without any genetic modification. Mouse embryoid bodies (EBs) were used screen library 1,000 identify compounds capable inducing levels Pax3 mRNA. Stimulation EBs SMIs (skeletal inducer,...