- RNA Research and Splicing
- Muscle Physiology and Disorders
- Cardiomyopathy and Myosin Studies
- RNA modifications and cancer
- Sleep and Wakefulness Research
- Microtubule and mitosis dynamics
- Neuroscience and Neuropharmacology Research
- RNA and protein synthesis mechanisms
- Cellular Mechanics and Interactions
- Circadian rhythm and melatonin
- Protein Kinase Regulation and GTPase Signaling
- Cancer Research and Treatments
- Genetic Neurodegenerative Diseases
- Neuroscience of respiration and sleep
- Photoreceptor and optogenetics research
- Dietary Effects on Health
- Developmental Biology and Gene Regulation
- TGF-β signaling in diseases
- Neurogenetic and Muscular Disorders Research
- Gene expression and cancer classification
- Protease and Inhibitor Mechanisms
- Cellular transport and secretion
- Diet and metabolism studies
- Retinal Diseases and Treatments
- Hippo pathway signaling and YAP/TAZ
Ludwig-Maximilians-Universität München
2019-2024
University College Dublin
2013-2020
United States Military Academy
2010-2014
Merck (Japan)
2013
Merck & Co., Inc., Rahway, NJ, USA (United States)
2010
University of Pennsylvania
2005-2010
The Wistar Institute
2009
To address whether changes in gene expression blood cells with sleep loss are different individuals resistant and sensitive to deprivation.Blood draws every 4 h during a 3-day study: 24-h normal baseline, 38 of continuous wakefulness subsequent recovery sleep, for total 19 time-points per subject, 2-h psychomotor vigilance task (PVT) assessment when awake.Sleep laboratory.Fourteen subjects who were previously identified as behaviorally (n = 7) or deprivation by PVT.Thirty-eight hours...
Migrating cells need to coordinate distinct leading and trailing edge dynamics but the underlying mechanisms are unclear. Here, we combine experiments mathematical modeling elaborate minimal autonomous biochemical machinery necessary sufficient for this dynamic coordination cell movement. RhoA activates Rac1 via DIA inhibits ROCK, while through PAK. Our data suggest that in motile, polarized cells, RhoA–ROCK interactions prevail at rear, whereas RhoA-DIA dominate front where Rac1/Rho...
Abstract Background The TGF-β/SMAD pathway is part of a broader signaling network in which crosstalk between pathways occurs. While the molecular mechanisms have been studied detail, global networks downstream SMAD remain largely unknown. regulatory effect complex likely depends on transcriptional modules, binding elements and partner transcription factor sites (SMAD modules) are present specific context. Results To address this question develop computational model for we simultaneously...
Study Objectives:Increases in ATP production machinery have been described brain after 3 h of sleep deprivation. Whether this is sustained with longer durations extended wakefulness unknown. We hypothesized that energy depletion could be a mechanism leading to difficulty maintaining and assessed changes components the electron transport chain.
Muscles undergo developmental transitions in gene expression and alternative splicing that are necessary to refine sarcomere structure contractility. CUG-BP ETR-3-like (CELF) family RNA-binding proteins important regulators of RNA processing during myogenesis misregulated diseases such as Myotonic Dystrophy Type I (DM1). Here, we report a conserved function for Bruno 1 (Bru1, Arrest), CELF1/2 homolog Drosophila , early muscle myogenesis. Loss Bru1 flight muscles results disorganization the...
Abstract Adenosine plays a role in promoting sleep, an effect that is thought to be mediated the basal forebrain. levels vary this region with prolonged wakefulness unique way. The basis for unknown. We examined, rats, activity of major metabolic enzymes adenosine – deaminase, kinase, ecto‐ and cytosolic 5′‐nucleotidase sleep/wake regulatory regions as well cerebral cortex, how varies across day sleep deprivation. There were robust spatial differences ecto‐5′‐nucleotidase. However, forebrain...
Increased mRNA level of subunit 1 cytochrome c oxidase (COXI) during wakefulness and after short-term sleep deprivation has been described in brain. We hypothesized that this might contribute to increased activity (COX) enzyme wakefulness, as part the mechanisms provide sufficient amounts adenosine triphosphate meet neuronal energy demands. COX was measured isolated mitochondria from different brain regions groups rats with 3 hours spontaneous sleep, wake, deprivation. The group wake added...
To assess differences in gene expression cholinergic basal forebrain cells between sleeping and sleep-deprived mice sacrificed at the same time of day. Tg(ChAT-eGFP)86Gsat expressing enhanced green fluorescent protein (eGFP) under control choline acetyltransferase (Chat) promoter were utilized to guide laser capture forebrain. Messenger RNA levels these profiled using microarrays. Gene eGFP(+) neurons was compared (1) that eGFP(−) adjacent white matter, (2) 7:00 am (lights on) pm off), (3)...
Previously, we showed that transient inhibition of TGF- β1 resulted in correction key aspects diabetes-induced CD34+ cell dysfunction. In this report, examine the effect plasminogen activator inhibitor-1 (PAI-1), a major gene target TGF-β1 activation. Using array studies, examined cells isolated from cohort longstanding diabetic individuals, free microvascular complications despite suboptimal glycemic control, and found exhibited reduced transcripts both PAI-1 compared to age, sex, degree...
A network of the Rho family GTPases, which cycle between inactive GDP-bound and active GTP-bound states, controls key cellular processes, including proliferation migration. Activating deactivating GTPase transitions are controlled by guanine nucleotide exchange factors (GEFs), activating proteins (GAPs) GDP dissociation inhibitors (GDIs) that sequester GTPases from membrane to cytoplasm. Here we show a cascade two RhoA Rac1, regulated RhoGDI1, exhibits distinct modes dynamic behavior,...
Drosophila flight muscle is a powerful model to study diverse processes such as transcriptional regulation, alternative splicing, metabolism, and mechanobiology, which all influence development myofibrillogenesis. Omics data, those generated by mass spectrometry or deep sequencing, can provide important mechanistic insights into these biological processes. For approaches, it beneficial analyze tissue-specific samples increase both selectivity specificity of the omics fingerprints. Here we...
The proper regulation of RNA processing is critical for muscle development and the fine-tuning contractile ability among fiber-types. binding proteins (RBPs) regulate diverse steps in processing, including alternative splicing, which generates fiber-type specific isoforms structural that confer sarcomeres with distinct biomechanical properties. Alternative splicing disrupted diseases such as myotonic dystrophy dilated cardiomyopathy altered after intense exercise well aging. It therefore...
Protein isoform transitions confer muscle fibers with distinct properties and are regulated by differential transcription alternative splicing. RNA-binding Fox protein 1 (Rbfox1) can affect both transcript levels splicing, is known to contribute normal development physiology in vertebrates, although the detailed mechanisms remain obscure. In this study, we report that Rbfox1 contributes generation of adult diversity Drosophila . differentially expressed among fiber types, RNAi knockdown...
Alternative splicing (AS) of introns from pre-mRNA produces diverse sets transcripts across cell types and tissues, but is also dysregulated in many diseases. Alignment-free computational methods have greatly accelerated the quantification mRNA short RNA-seq reads, they inherently rely on a catalog known might miss novel, disease-specific events. By contrast, alignment reads to genome can effectively identify novel exonic segments introns. Event-based then count how align predefined...
Alterations in choroid plexus gene expression Alzheimer’s disease provide inferences for CSF composition and dynamics Miles C Miller, Edward G Stopa, Elena V Nikonova, Keith Q Tanis, Alexei A Podtelezhnikov, Eva M Finney, David J Stone, Luiz Camargo, Lisan Parker, Ajay Verma, Andrew Baird, John E Donahue, Ana Maria Gonzalez, Brian Eliceiri, Gerald D Silverberg, Petra Klinge, Conrad Johanson
Drosophila flight muscle is a powerful model to study diverse processes such as transcriptional regulation, alternative splicing, metabolism, and mechanobiology, which all influence development myofibrillogenesis. Omics data, those generated by mass spectrometry or deep sequencing, can provide important mechanistic insights into these biological processes. For approaches, it beneficial analyze tissue-specific samples increase both selectivity specificity of the omics fingerprints. Here we...
The proper regulation of RNA processing is critical for muscle development and the fine-tuning contractile ability between fiber-types. binding proteins (RBPs) regulate diverse steps in including alternative splicing, which generates fiber-type specific isoforms structural that confer sarcomeres with distinct biomechanical properties. Alternative splicing disrupted diseases such as myotonic dystrophy dilated cardiomyopathy, altered after intense exercise well aging. It therefore important to...
Abstract Migrating cells need to coordinate distinct leading and trailing edge dynamics but the underlying mechanisms are unclear. Here, we combine experiments mathematical modeling elaborate minimal autonomous biochemical machinery necessary sufficient for this dynamic coordination cell movement. RhoA activates Rac1 via DIA inhibits ROCK, while through PAK. Our data suggest that in motile, polarized cells, RhoA–ROCK interactions prevail at rear whereas RhoA-DIA dominate front where Rac1/Rho...
Abstract Protein isoform transitions confer distinct properties on muscle fibers and are regulated predominantly by differential transcription alternative splicing. RNA-binding Fox protein 1 (Rbfox1) can affect both transcript levels splicing, is known to control skeletal function. However, the detailed mechanisms which Rbfox1 contributes normal development physiology remain obscure. In this study, we report that generation of adult diversity in Drosophila . differentially expressed tubular...
Supplementary Figures 1-6, Table 1 from Sp100 as a Potent Tumor Suppressor: Accelerated Senescence and Rapid Malignant Transformation of Human Fibroblasts through Modulation an Embryonic Stem Cell Program
Supplementary Figures 1-6, Table 1 from Sp100 as a Potent Tumor Suppressor: Accelerated Senescence and Rapid Malignant Transformation of Human Fibroblasts through Modulation an Embryonic Stem Cell Program