- Cell Image Analysis Techniques
- Image Processing Techniques and Applications
- Advanced Fluorescence Microscopy Techniques
- Genetics, Bioinformatics, and Biomedical Research
- RNA Research and Splicing
- Single-cell and spatial transcriptomics
- HIV Research and Treatment
- interferon and immune responses
- Streptococcal Infections and Treatments
- X-ray Diffraction in Crystallography
- Zebrafish Biomedical Research Applications
- Fungal Infections and Studies
- Aquaculture disease management and microbiota
- Asthma and respiratory diseases
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Immune Cell Function and Interaction
- Advanced Electron Microscopy Techniques and Applications
- Cytomegalovirus and herpesvirus research
- Mycobacterium research and diagnosis
- Crystallization and Solubility Studies
- HER2/EGFR in Cancer Research
- Hippo pathway signaling and YAP/TAZ
- Immune cells in cancer
- AI in cancer detection
- Sarcoma Diagnosis and Treatment
Broad Institute
2020-2024
Software (Spain)
2023
Massachusetts Institute of Technology
2023
University College London
2018-2020
Harvard University
2020
The University of Texas Southwestern Medical Center
2020
Institute of Infection and Immunity
2020
The Royal Free Hospital
2019
Molecular Discovery (United Kingdom)
2018
GlaxoSmithKline (United Kingdom)
2018
Abstract Background Imaging data contains a substantial amount of information which can be difficult to evaluate by eye. With the expansion high throughput microscopy methodologies producing increasingly large datasets, automated and objective analysis resulting images is essential effectively extract biological from this data. CellProfiler free, open source image program enables researchers generate modular pipelines with process into interpretable measurements. Results Herein we describe...
Image-based experiments can yield many thousands of individual measurements describing each object interest, such as cells in microscopy screens. CellProfiler Analyst is a free, open-source software package designed for the exploration quantitative image-derived data and training machine learning classifiers with an intuitive user interface. We have now released 3.0, which addition to enhanced performance adds support neural network classifiers, identifying rare subsets, direct transfer...
A growing community is constructing a next-generation file format (NGFF) for bioimaging to overcome problems of scalability and heterogeneity. Organized by the Open Microscopy Environment (OME), individuals institutes across diverse modalities facing these have designed specification process (OME-NGFF) address needs. This paper brings together wide range those members describe cloud-optimized itself-OME-Zarr-along with tools data resources available today increase FAIR access remove barriers...
A primary obstacle in translating genetic associations with disease into therapeutic strategies is elucidating the cellular programs affected by risk variants and effector genes. Here, we introduce LipocyteProfiler, a cardiometabolic-disease-oriented high-content image-based profiling tool that enables evaluation of thousands morphological profiles can be systematically linked to genes relevant cardiometabolic disease. We show LipocyteProfiler allows surveillance diverse generating rich...
The glucocorticoid receptor (GR) is a major drug target in inflammatory disease. However, chronic (GC) treatment leads to disordered energy metabolism, including increased weight gain, adiposity, and hepatosteatosis - all programs modulated by the circadian clock. We demonstrated that while antiinflammatory GC actions were maintained irrespective of dosing time, liver was significantly more sensitive during day. Temporal segregation action underpinned physical interaction GR with...
Abstract TCR-gene-transfer is an efficient strategy to produce therapeutic T cells of defined antigen specificity. However, there are substantial variations in the cell surface expression levels human TCRs, which can impair function engineered cells. Here we demonstrate that substitutions 3 amino acid residues framework TCR variable domains consistently increase TCRs on cells.The modified mediate enhanced proliferation, cytokine production and cytotoxicity, while reducing peptide...
HIV-1 must replicate in cells that are equipped to defend themselves from infection through intracellular innate immune systems. evades sensing encapsidated DNA synthesis and encodes accessory genes antagonize specific antiviral effectors. Here, we show both particle associated, expressed Vpr, the stimulatory effect of a variety pathogen associated molecular patterns by inhibiting IRF3 NF-κB nuclear transport. Phosphorylation at S396, but not S386, was also inhibited. We propose that, rather...
To determine the effect of two forms warm-up on postexercise bronchoconstriction in athletes with exercise-induced asthma, 12 moderately trained persons asthma (age = 26.5 +/- 2.2 yr; height 169.2 2.6 cm; weight 64.3 2.6kg; VO2max 52.7 1.3 ml.kg-1.min-1) were tested under three experimental conditions; continuous (CW), interval (IW), and control (C). CW consisted 15 min treadmill running at a velocity corresponding to 60% followed by an exercise challenge test (ET 6 90% VO2max). IW involved...
Drug resistance is a challenge in anticancer therapy. In many cases, cancers can be resistant to the drug prior exposure, that is, possess intrinsic resistance. However, we lack target-independent methods anticipate cancer cell lines or characterize without priori knowledge of its cause. We hypothesized morphology could provide an unbiased readout To test this hypothesis, used HCT116 cells, mismatch repair-deficient line, isolate clones were sensitive bortezomib, well-characterized...
A growing community is constructing a next-generation file format (NGFF) for bioimaging to overcome problems of scalability and heterogeneity. Organized by the Open Microscopy Environment (OME), individuals institutes across diverse modalities facing these have designed specification process (OME-NGFF) address needs. This paper brings together wide range those members describe cloud-optimized itself -- OME-Zarr along with tools data resources available today increase FAIR access remove...
Abstract In order to determine the influence of two artificially induced alkalotic states on ability perform maximal exercise, six male subjects (mean age, 22.0 years; mean height, 176.8 cm; weight, 69.1 kg; VO2 max, 3.83 1 min‐1) were studied during three experimental trials. The performed 60‐s cycling bouts, at a work rate corresponding 125% with 60 s recovery between bouts; these regimes h after ingestion solution containing either: I, placebo; II, NaHCO3 in dosage 0.15 g per kg body...
In 10 nonasthmatic subjects and 11 patients with asthma, we measured pulmonary resistance (RL), functional residual capacity (FRC), specific conductance (sGaw) before, during, after submaximal treadmill exercise. Nonasthmatic did not change RL, FRC, or sGaw from base-line resting values during RL decreased significantly exercise, both when exercise was begun the control state conditions of elevated a preceding period When asthmatic inhaled standardized dose aerosolized histamine, increase in...
CellProfiler is a widely used software for creating reproducible, reusable image analysis workflows without needing to code. In addition the >90 modules that make up main program, has plugins system allows creation of new which integrate with other Python tools or are packaged in containers. The CellProfiler-plugins repository contains number these modules, especially experimental and/or dependency-heavy. Here, we present an upgraded repository, example accessing containerised tools,...
Salbutamol and treadmill performance in non-atopic athletes. Med. Sci. Sports Exerc., Vol. 15, No. 6, pp. 520-522, 1983. Nineteen aerobic, non-atopic, athletes (10 females, 9 males) were studied a double-blind fashion to determine the effect of therapeutic dosage salbutamol on pulmonary function, oxygen consumption (VO2max), heart rate (HR), anaerobic threshold (AT). A placebo (in aerosol form) administered two puffs four times per day. Forced vital capacity (FVC), FEV1.0, mid-maximal...
Cryptococcus neoformans is an opportunistic human pathogen, which causes serious disease in immunocompromised hosts. Infection with this pathogen particularly relevant HIV+ patients, where it leads to around 200,000 deaths per annum. A key feature of cryptococcal pathogenesis the ability fungus survive and replicate within phagosome macrophages, as well its be expelled from host cells via a novel non-lytic mechanism known vomocytosis. Here we show that vomocytosis macrophages strongly...
Abstract We describe new open source software called QuantiFish for rapid quantitation of fluorescent foci in zebrafish larvae, to support infection research this animal model. extends the conventional measurements bacterial load and number include measures dissemination infection. These are represented by proportions bacteria between their spatial distribution. showcase these comparison intravenous hindbrain routes Mycobacterium marinum infection, which indistinguishable measurement not...
Abstract Background Imaging data contains a substantial amount of information which can be difficult to evaluate by eye. With the expansion high throughput microscopy methodologies producing increasingly large datasets, automated and objective analysis resulting images is essential effectively extract biological from this data. CellProfiler free, open source image program enables researchers generate modular pipelines with process into interpretable measurements. Results Herein we describe...
The polytopic ligands 2poap and po2p have a linear disposition of coordination pockets suitably disposed to bind metal ions in close proximity produce trinuclear copper(II) complexes. complexes [Cu3(2poap − 2H)(CH3CO2)4]·3H2O (1), 2H)(H2O)(DMF)3(CH3OH)2](BF4)4 (2), [Cu3(po2p H)2(H2O)2](ClO4)4·2H2O (3) arrangement Cu(II) centres linked by trans N–N single bonds. Each is assigned dx2 y2 magnetic ground state, the diazine bridging leads strong antiferromagnetic coupling complete agreement with...
Summary A primary obstacle in translating genetics and genomics data into therapeutic strategies is elucidating the cellular programs affected by genetic variants genes associated with human diseases. Broadly applicable high-throughput, unbiased assays offer a path to rapidly characterize gene variant function thus illuminate disease mechanisms. Here, we report LipocyteProfiler, an high-content microscopy assay that amenable large-scale morphological profiling of lipid-accumulating cell...
Abstract We herein describe a postdoctoral training program designed to train biologists with microscopy experience in bioimage analysis. detail the rationale behind program, various components of and outcomes terms works produced career effects on past participants. analyze results an anonymous survey distributed present participants, indicating overall high value all 12 rated aspects but significant heterogeneity which were most important each participant. Finally, we propose this model as...
Deep learning has greatly accelerated research in biological image analysis yet it often requires programming skills and specialized tool installation. Here we present Piximi, a modern, no-programming leveraging deep learning. Implemented as web application at Piximi.app, Piximi no installation can be accessed by any modern browser. Its client-only architecture preserves the security of researcher data running all computation locally. offers four core modules: classifier, an annotator,...
ABSTRACT Drug resistance is a challenge in anticancer therapy, particularly with targeted therapeutics and cytotoxic compounds. In many cases, cancers can be resistant to the drug prior exposure, i.e., possess intrinsic resistance. However, we lack target-independent methods anticipate cancer cell lines or characterize without priori knowledge of its cause. We hypothesized that morphology could provide an unbiased readout sensitivity treatment. therefore isolated clonal were either sensitive...
Abstract Cryptococcus neoformans is an opportunistic human pathogen, which causes serious disease in immunocompromised hosts. Infection with this pathogen particularly relevant HIV+ patients, where it leads to around 200,000 deaths per annum . A key feature of cryptococcal pathogenesis the ability fungus survive and replicate within phagosome macrophages, as well its escape via a novel non-lytic mechanism known vomocytosis. We have been exploring whether viral infection affects interaction...