A5037894626- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Complement system in diseases
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Neuropeptides and Animal Physiology
- Barrier Structure and Function Studies
- Single-cell and spatial transcriptomics
- Research on Leishmaniasis Studies
- RNA Research and Splicing
- Phytochemical compounds biological activities
- Cancer-related molecular mechanisms research
- Tryptophan and brain disorders
- RNA modifications and cancer
- Piperaceae Chemical and Biological Studies
- Immune cells in cancer
- Gene Regulatory Network Analysis
- Enzyme function and inhibition
- Biochemical Acid Research Studies
University of California, Irvine
2021-2024
Universidade Federal do Oeste da Bahia
2015
Universidade Federal do Rio de Janeiro
2015
The majority of mammalian genes encode multiple transcript isoforms that result from differential promoter use, changes in exonic splicing, and alternative 3' end choice. Detecting quantifying across tissues, cell types, species has been extremely challenging because transcripts are much longer than the short reads normally used for RNA-seq. By contrast, long-read RNA-seq (LR-RNA-seq) gives complete structure most transcripts. We sequenced 264 LR-RNA-seq PacBio libraries totaling over 1...
Abstract Multiple studies have recognized the involvement of complement cascade during Alzheimer’s disease pathogenesis. However, specific role C5a-C5aR1 signaling in progression this neurodegenerative is still not clear. Furthermore, its potential as a therapeutic target to treat AD remains be elucidated. Canonically, generation anaphylatoxin C5a result activation and interaction with receptor C5aR1 triggers potent inflammatory response. Previously, genetic ablation mouse model exerted...
The complement system is part of the innate immune that clears pathogens and cellular debris. In healthy brain, influences neurodevelopment neurogenesis, synaptic pruning, clearance neuronal blebs, recruitment phagocytes, protects from pathogens. However, excessive downstream activation leads to generation C5a, C5a engagement with its receptor C5aR1, instigates a feed-forward loop inflammation, injury, death, making C5aR1 potential therapeutic target for neuroinflammatory disorders. ablation...
Alzheimer's disease (AD) is the leading cause of dementia in older adults, and need for effective, sustainable therapeutic targets imperative. The complement pathway has been proposed as a target. C5aR1 inhibition reduces plaque load, gliosis, memory deficits animal models, however, cellular bases underlying this neuroprotection were unclear. Here, we show that antagonist PMX205 improves outcomes Arctic48 mouse model AD. A combination single cell nucleus RNA-seq analysis hippocampi derived...
Summary Gene regulatory networks (GRNs) provide a powerful framework for studying cellular differentiation. However, it is less clear how GRNs encode responses to everyday microenvironmental cues. Macrophages can be polarized and potentially repolarized based on environmental signaling. In order identify the that drive macrophage polarization heterogeneous single-cell subpopulations are present in process, we used high-resolution time course of bulk RNA-seq ATAC-seq assays HL-60-derived...
ABSTRACT Multiple mouse models have been generated that strive to recapitulate human Alzheimer’s disease (AD) pathological features investigate mechanisms and potential treatments. The 3xTg-AD presents the two major hallmarks of AD, which are plaques tangles increase during aging. While behavioral changes accumulation well described in mice, subpopulations neurons glial cells present throughout progression not characterized. Here, we used single-cell RNA-seq microglia, single-nucleus explore...
Alzheimer's disease (AD) is the leading cause of dementia in older adults, and need for effective, sustainable therapeutic targets imperative. Pharmacologic inhibition C5aR1 reduces plaque load, gliosis memory deficits animal models. However, cellular basis underlying this neuroprotection which processes were consequence amyloid reduction vs alteration response to unclear. In Arctic model, antagonist PMX205 did not reduce but short-term female mice prevented. Hippocampal single cell nucleus...
Polyphosphates have been found in all cell types examined to date and play diverse roles depending on the type. In eukaryotic organisms, polyphosphates mainly investigated mammalian cells with few studies insects. Some demonstrated that a pyrophosphatase regulates polyphosphate metabolism, most of them were performed trypanosomatids. Here, we effects sPPase gene knocked down oogenesis metabolism red flour beetle (Tribolium castaneum). A single was identified insect genome is maternally...
Abstract Polyphosphates (polyPs) have been found in all cell types examined to date and play diverse roles, depending on the type. In eukaryotic organisms, polyPs mainly investigated mammalian cells, with few studies insects. this study, we mitochondrial polyphosphate metabolism red flour beetle, Tribolium castaneum . Substrate specificity for different chain lengths demonstrated presence of two exopolyphosphatase isoforms mitochondria. T. polyP levels decreased after injection soluble...
Abstract Background The complement system is part of the innate immune that clears pathogens and cellular debris. In healthy brain, influences neurodevelopment neurogenesis, synaptic pruning, clearance neuronal blebs, recruitment phagocytes, protects from pathogens. However, excessive downstream activation leads to generation C5a, C5a engagement with its receptor C5aR1, instigates a feed-forward loop inflammation, injury, death, making C5aR1 potential therapeutic target for neuroinflammatory...
Abstract Multiple studies have recognized the involvement of complement cascade during Alzheimer’s disease pathogenesis; however, specific role C5a-C5aR1 signaling in progression this neurodegenerative is still not clear. Furthermore, its potential as a therapeutic target to treat AD remains be elucidated. Canonically, generation anaphylatoxin C5a result activation and interaction with receptor C5aR1 triggers potent inflammatory response. Previously, genetic ablation mouse model exerted...
Abstract Background Upregulation of complement genes in Alzheimer’s disease (AD) mouse models is associated with inflammation and cognitive decline. Genetic ablation C5aR1 reduces loss neuronal complexity cognition the Arctic model. Inhibition PMX205 has shown success preclinical studies AD, reducing recruitment reactive glia amyloid deposition Tg2576 AD However, molecular cellular mechanisms underlying this neuroprotection are unclear. Thus, we used single cell RNA‐seq to interrogate gene...