A5030512799- Single-cell and spatial transcriptomics
- Immune cells in cancer
- Immune responses and vaccinations
- SARS-CoV-2 and COVID-19 Research
- Neuroinflammation and Neurodegeneration Mechanisms
- COVID-19 Clinical Research Studies
- Barrier Structure and Function Studies
- Cancer Cells and Metastasis
- S100 Proteins and Annexins
- Birth, Development, and Health
- Diabetes and associated disorders
- Sarcoma Diagnosis and Treatment
- Liver Disease Diagnosis and Treatment
- Chronic Kidney Disease and Diabetes
- Pregnancy and preeclampsia studies
- Oral and Maxillofacial Pathology
- Olfactory and Sensory Function Studies
- Viral Infections and Immunology Research
- Cancer, Hypoxia, and Metabolism
- COVID-19 Impact on Reproduction
- Machine Learning and Algorithms
- Neuroscience, Education and Cognitive Function
- Clusterin in disease pathology
- Neural Networks and Applications
- Crop Yield and Soil Fertility
Nanostring Technologies (United States)
2021-2025
University of California, Riverside
2022-2023
Stanford University
2021
University of Washington
2020
Highlights•A postmortem bedside surgical procedure was developed for COVID-19 and control patients•Ciliated cells are the main target cell type SARS-CoV-2 in respiratory mucosa•Sustentacular (non-neuronal) olfactory mucosa•No evidence infection of sensory neurons or bulb parenchymaSummaryAnosmia, loss smell, is a common often sole symptom COVID-19. The onset sequence pathobiological events leading to dysfunction remains obscure. Here, we have harvest endoscopically samples mucosae whole...
Thymus is necessary for lifelong immunological tolerance and immunity. It displays a distinctive epithelial complexity undergoes age-dependent atrophy. Nonetheless, it also retains regenerative capacity, which, if harnessed appropriately, might permit rejuvenation of adaptive By characterizing cortical medullary compartments in the human thymus at single-cell resolution, this study we have defined specific populations, including those that share properties with bona fide stem cells (SCs)...
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus infection in pregnancy is associated with higher incidence of placental dysfunction, referred to by a few studies as 'preeclampsia-like syndrome'. However, the mechanisms underpinning SARS-CoV-2-induced malfunction are still unclear. Here, we investigated whether transcriptional architecture placenta altered response SARS-CoV-2 infection.
Abstract Background The molecular underpinnings of organ dysfunction in severe COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these the context liver function, we perform single-nucleus RNA-seq spatial transcriptomic profiling livers from 17 decedents. Results We identify hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells, a central role pro-fibrotic TGFβ signaling cell–cell...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to present with pulmonary and extra-pulmonary organ complications. In comparison the 2009 pandemic (pH1N1), SARS-CoV-2 infection likely lead more disease, multi-organ effects, including cardiovascular disease. has been associated long-term but molecular changes that govern this remain unknown. study, we investigated host transcriptome landscape of cardiac tissues collected at rapid autopsy from seven SARS-CoV-2, two...
Maize shoot development progresses from non-pigmented meristematic cells at the base of leaf to expanded and non-dividing green blade. This transition is accompanied by conversion promitochondria proplastids their mature forms massive fragmentation both mitochondrial DNA (mtDNA) plastid (ptDNA), collectively termed organellar (orgDNA). We measured developmental changes in reactive oxygen species (ROS), which high concentrations can lead oxidative stress damage, as well antioxidant agents...
Abstract In vitro, ACE2 translocates to the nucleus induce SARS-CoV-2 replication. Here, using digital spatial profiling of lung tissues from SARS-CoV-2-infected golden Syrian hamsters, we show that a specific and selective peptide inhibitor nuclear (NACE2i) inhibits viral replication two days after infection. Moreover, also prevents inflammation macrophage infiltration, increases NK cell infiltration in bronchioles. NACE2i treatment levels active histone mark, H3K27ac, restores host...
Abstract We developed Standardised Minimum 3D Distance (SM3DD), an entirely cell segmentation/annotation-free approach to the analysis of spatial RNA datasets, using it compare lung tissue from 16 clinically normal individuals those 18 SARS-CoV-2 patients who died acute respiratory distress syndrome. coordinates were determined CosMx™ Spatial Molecular Imager (Bruker Biology, US). For each individual transcript location, we calculated three-dimensional distances nearest type, standardising...
The SARS-CoV-2 (COVID-19) virus has caused a devastating global pandemic of respiratory illness. To understand viral pathogenesis, methods are available for studying dissociated cells in blood, nasal samples, bronchoalveolar lavage fluid and similar, but robust platform deep tissue characterization molecular cellular responses to infection the lungs is still lacking. We developed an innovative spatial multi-omics investigate COVID-19-infected lung tissues. Five tissue-profiling technologies...
Abstract Stroke is ranked as the fifth leading cause of death and adult disability in USA. The progression neuronal damage after stroke recognized to be a complex integration glia, neurons, surrounding extracellular matrix, therefore potential treatments must target detrimental effects created by these interactions. In this study, we examined spatial cellular neuroinflammatory mechanisms occurring early ischemic utilizing Nanostring Digital Spatial Profiling (DSP) technology. Male C57bl/6...
The molecular underpinnings of organ dysfunction in acute COVID-19 and its potential long-term sequelae are under intense investigation. To shed light on these the context liver function, we performed single-nucleus RNA-seq spatial transcriptomic profiling livers from 17 decedents. We identified hepatocytes positive for SARS-CoV-2 RNA with an expression phenotype resembling infected lung epithelial cells. Integrated analysis comparisons healthy controls revealed extensive changes cellular...
Abstract Maladaptive proximal tubular cells have been implicated in failure of repair following renal injury rodent models, however whether this translates to human kidney disease is unknown. Hence, we integrated snRNA-ATAC-seq with single-cell molecular imaging generate a multiomic atlas disease. In injured kidneys, subset epithelial acquired an inflammatory phenotype, enriched pro-fibrotic and senescence markers, analogous maladaptive mice. Cell neighborhood analysis positioned the...
Stromal cells are key components of the tumour microenvironment (TME) and their incorporation into 3D engineered tumour-stroma models is essential for mimicry. By engineering tumouroids with distinct stromal compartments, it has been possible to identify how gene expression altered influenced by presence different cells. Ameloblastoma a benign epithelial jawbone. In engineered, multi-compartment spatial transcriptomics revealed an upregulation oncogenes in ameloblastoma transcriptome where...
Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to present with pulmonary and extra-pulmonary organ complications. In comparison the 2009 pandemic (pH1N1), SARS-CoV-2 infection likely lead more disease, multi-organ effects, including cardiovascular disease. has been associated long-term but molecular changes govern this remain unknown. study, we investigated landscape of cardiac tissues collected at rapid autopsy from SARS-CoV-2, pH1N1, control patients...
Abstract The SARS-CoV-2 (COVID-19) virus has caused a devastating global pandemic of respiratory illness. To understand viral pathogenesis, methods are available for studying dissociated cells in blood, nasal samples, bronchoalveolar lavage fluid, and similar, but robust platform deep tissue characterisation molecular cellular responses to infection the lungs is still lacking. We developed an innovative spatial multi-omics investigate COVID-19-infected lung tissues. Five tissue-profiling...
Abstract Understanding the physiology and functions of liver cancer requires knowing transcriptional patterns driving biological activities within functional structures tissue, especially zonated features metabolic networks. Using powerful unique capabilities GeoMx® Digital Spatial Profiler (DSP) with Whole Transcriptome Atlas (WTA) panel to resolve units FFPE tissues in situ, here we report spatial analysis whole transcriptomes across three micro-dissected zones (pericentral zone 3,...
The biological behaviour of the cancer cell is in part controlled by its microenvironment and underlying genetics. interaction cells with surrounding stroma directs progression. most common primary malignant tumour bone, osteosarcoma, a highly complex disease terms progression, invasion, metastasis. To better understand characteristics develop accurate therapies for novel tissue models have been developed to systematically how facets (TME) can influence behaviour. This study aims...
Abstract Cellular senescence drives organ fibrosis and ageing, accumulating evidence supports the ability of senescence-depleting drugs to improve outcomes in experimental models disease. The lack non-invasive biomarkers represents a major obstacle design human trials candidate senolytics. On samples from 51 patients with chronic kidney disease (CKD), we performed liquid chromatography mass spectrometry (LC-MS) analysis urine alongside immunofluorescence staining paired biopsies for p21,...
Neural networks have long been used to model human intelligence, capturing elements of behavior and cognition, their neural basis. Recent advancements in deep learning enabled network models reach even surpass levels intelligence many respects, yet unlike humans, ability learn new tasks quickly remains a challenge. People can reason not only familiar domains, but also rapidly through novel problems situations, raising the question how well modern capture which ways they diverge. In this...
Abstract Bioengineering facets of the tumour microenvironment (TME) are essential in 3D tissue models to accurately recapitulate progression. Stromal cells key components TME and their incorporation into biomimetic bioengineered tumour-stroma is be able mimic TME. By engineering tumouroids with distinct stromal compartments, it has been possible identify how gene expression altered by presence different using spatial transcriptomics. Ameloblastoma a benign epithelial jawbone engineered...
Abstract Neuregulin-1 (NRG-1) has been shown to be neuroprotective and anti-inflammatory in rodent models following focal brain ischemia. However, the spatial transcriptional mechanisms involved effects of NRG-1 have not investigated. In this study, we examined cellular neuroinflammatory employed by stroke utilizing Nanostring Digital Spatial Profiling (DSP) technology. C57bl/6 mice were subjected photothrombotic middle cerebral artery occlusion (MCAO). Animals treated with (5ug/kg/day β) or...
ABSTRACT Objectives Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus infection in pregnancy is associated with higher incidence of placental dysfunction, referred to by a few studies as “preeclampsia-like syndrome”. However, the mechanisms underpinning SARS-CoV-2-induced malfunction are still unclear. Here, we investigated whether transcriptional architecture placenta altered response SARS-CoV-2 infection. Methods We utilized whole-transcriptome, digital spatial profiling,...
<h3>Background</h3> Immunological mechanisms regulating detection and clearance of cancer, including CTLA-4 PD-L1, were discovered by studying the natural physiological processes immune cell maturation, attenuation, dissemination throughout body. Single-cell atlases mapping cells provide hints to these aspects immunology but lack essential spatio-temporal relationships between cells. With advent spatial 'omics we can resolve thousands RNA or more than 60 protein molecules simultaneously<i>...