A5012378359- Single-cell and spatial transcriptomics
- T-cell and B-cell Immunology
- Advanced biosensing and bioanalysis techniques
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Chronic Lymphocytic Leukemia Research
- Extracellular vesicles in disease
- CRISPR and Genetic Engineering
- Immunotherapy and Immune Responses
- Immunodeficiency and Autoimmune Disorders
- Neuroscience and Neuropharmacology Research
- RNA Research and Splicing
- Mitochondrial Function and Pathology
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cell Image Analysis Techniques
- ATP Synthase and ATPases Research
- Neuroscience and Neural Engineering
- Cancer-related molecular mechanisms research
- Psoriasis: Treatment and Pathogenesis
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Gene expression and cancer classification
- Cancer Mechanisms and Therapy
- IL-33, ST2, and ILC Pathways
- Advanced Biosensing Techniques and Applications
- Protein Kinase Regulation and GTPase Signaling
Columbia University Irving Medical Center
2023-2025
Columbia University
2021-2025
New York Genome Center
2023-2025
New York Proton Center
2024
Broad Institute
2015-2020
Harvard University
2012-2015
Harvard University Press
2011-2013
Single-nucleus RNA-seq (snRNA-seq) enables the interrogation of cellular states in complex tissues that are challenging to dissociate or frozen, and opens way human genetics studies, clinical trials, precise cell atlases large organs. However, such applications currently limited by batch effects, processing, costs. Here, we present an approach for multiplexing snRNA-seq, using sample-barcoded antibodies uniquely label nuclei from distinct samples. Comparing brain cortex samples profiled with...
A circuit level understanding of immune cells and hematological cancers has been severely impeded by a lack techniques that enable intracellular perturbation without significantly altering cell viability function. Here, we demonstrate vertical silicon nanowires (NWs) gene-specific manipulation diverse murine human with negligible toxicity. To illustrate the power technique, then apply NW-mediated gene silencing to investigate role Wnt signaling pathway in chronic lymphocytic leukemia (CLL)....
Unlike sequencing-based methods, which require cell lysis, optical pooled genetic screens enable investigation of spatial phenotypes, including morphology, protein subcellular localization, cell–cell interactions and tissue organization, in response to targeted CRISPR perturbations. Here we report a multimodal screening method, call CRISPRmap. CRISPRmap combines situ guide-identifying barcode readout with multiplexed immunofluorescence RNA detection. Barcodes are detected read out through...
Developing a detailed understanding of enzyme function in the context an intracellular signal transduction pathway requires minimally invasive methods for probing activity situ. Here, we describe new method monitoring living cells by sandwiching live between two vertical silicon nanowire (NW) arrays. Specifically, use first NW array to immobilize and then present enzymatic substrates intracellularly via second utilizing NWs' ability penetrate cellular membranes without affecting cells'...
Th17 cells are key players in defense against pathogens and maintaining tissue homeostasis, but also act as critical drivers of autoimmune diseases. Based on single-cell RNA-seq profiling pathogenic versus nonpathogenic cells, we identified protein C receptor (PROCR) a cell surface molecule expressed covariance with the regulatory module cells. Although PROCR expression T was controlled by cooperative action lineage-specific transcription factors RORγt, IRF4, STAT3, negatively regulated...
Abstract In neurons of the mammalian central nervous system (CNS), axonal mitochondria are thought to be indispensable for supplying ATP during energy-consuming processes such as neurotransmitter release. Here, we demonstrate using multiple, independent, in vitro and vivo approaches that majority (∼80-90%) cortical pyramidal (CPNs), lack mitochondrial DNA (mtDNA). Using dynamic, optical imaging analysis genetically encoded sensors matrix pH, axons CPNs, but not their dendrites, complex V...
Abstract Missense mutations in PTPN11 , the gene encoding protein tyrosine phosphatase SHP2, are common several developmental disorders and cancers. While many SHP2 disrupt auto-inhibition cause hyperactivity, do not enhance catalytic activity. Both activating non-activating could potentially drive pathogenic signaling by altering protein-protein interactions or subcellular localization. We employed proximity-labeling proteomics to map interaction networks of wild-type ten...
Abstract γδ T cells are a subset of lymphocytes specialized in protecting the host against pathogens and tumours. Here we describe regulatory that express latency-associated peptide (LAP), membrane-bound TGF-β1. Thymic CD27+IFN-γ+CCR9+α 4 β 7 +TCRγδ+ migrate to periphery, particularly Peyer’s patches small intestine lamina propria, where they upregulate LAP, downregulate IFN-γ via ATF-3 expression acquire phenotype. TCRγδ+LAP+ antigen presentation molecules function as presenting induce...
Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a promising platform for cardiac studies in vitro, and possibly tissue repair humans. However, hiPSC-CM cells tend to retain morphology, metabolism, patterns of gene expression, electrophysiology similar that embryonic cardiomyocytes. We grew patterned islands different sizes shapes, measured the effect island geometry on action potential waveform calcium dynamics using optical recordings voltage from 970 sizes. larger...
Pooled genetic screens are powerful tools to study gene function in a high-throughput manner. Typically, sequencing-based require cell lysis, which limits the examination of critical phenotypes such as morphology, protein subcellular localization, and cell-cell/tissue interactions. In contrast, emerging optical pooled screening methods enable investigation these spatial response targeted CRISPR perturbations. this study, we report multi-omic method, have named CRISPRmap. Our method combines...
Abstract Single-nucleus RNA-Seq (snRNA-seq) enables the interrogation of cellular states in complex tissues that are challenging to dissociate, including frozen clinical samples. This opens way, principle, large studies, such as those required for human genetics, trials, or precise cell atlases organs. However, applications currently limited by batch effects, sequential processing, and costs. To address these challenges, we present an approach multiplexing snRNA-seq, using sample-barcoded...