A5083255732- Zebrafish Biomedical Research Applications
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune cells in cancer
- Immune Response and Inflammation
- Neuroinflammation and Neurodegeneration Mechanisms
- Cellular Mechanics and Interactions
- Antifungal resistance and susceptibility
- 3D Printing in Biomedical Research
- Platelet Disorders and Treatments
- Microfluidic and Bio-sensing Technologies
- Bacterial biofilms and quorum sensing
- Inflammasome and immune disorders
- Cell Adhesion Molecules Research
- Blood disorders and treatments
- Sepsis Diagnosis and Treatment
- Congenital heart defects research
- Mosquito-borne diseases and control
- Aquaculture disease management and microbiota
- Neonatal and Maternal Infections
- Pluripotent Stem Cells Research
- COVID-19 Clinical Research Studies
- Bacterial Identification and Susceptibility Testing
- Receptor Mechanisms and Signaling
- Atherosclerosis and Cardiovascular Diseases
- Vector-borne infectious diseases
Harvard University
2016-2024
Massachusetts General Hospital
2016-2024
Shriners Hospitals for Children - Erie
2018-2023
Shriners Hospitals for Children - Boston
2016-2023
Stago (France)
2023
University of Sheffield
2015-2021
Immunité et Cancer
2020
Walter and Eliza Hall Institute of Medical Research
2008-2019
The University of Melbourne
2008-2019
Australian Regenerative Medicine Institute
2011-2019
Zebrafish (Danio rerio) embryos are increasingly used as a model for studying the function of vertebrate innate immune system in host-pathogen interactions 1. The major cell types system, macrophages and neutrophils, develop during first days embryogenesis prior to maturation lymphocytes that required adaptive responses. ease obtaining large numbers embryos, their accessibility due external development, optical transparency embryonic larval stages, wide range genetic tools, extensive mutant...
Neutrophil removal from inflammatory sites is regulated by lipid mediator signals between macrophages and neutrophils.
Chikungunya Virus (CHIKV), a re-emerging arbovirus that may cause severe disease, constitutes an important public health problem. Herein we describe novel CHIKV infection model in zebrafish, where viral spread was live-imaged the whole body up to cellular resolution. Infected cells emerged various organs one principal wave with median appearance time of ∼14 hours post infection. Timing infected cell death organ dependent, leading shift localization towards brain. As mammals, triggered strong...
Autosomal recessively inherited glucocerebrosidase 1 (GBA1) mutations cause the lysosomal storage disorder Gaucher's disease (GD). Heterozygous GBA1 (GBA1+/−) are most common risk factor for Parkinson's (PD). Previous studies typically focused on interaction between reduction of (enzymatic) activity in GBA1+/− carriers and alpha-synuclein-mediated neurotoxicity. However, it is unclear whether other mechanisms also contribute to increased PD carriers. The zebrafish genome does not contain...
Significance Acinetobacter baumannii is one of the most significant hospital-acquired bacterial pathogens, able to cause life-threatening infections and develop resistance all currently available antibiotic agents. Here, we established zebrafish as a model study real-time interactions between innate immune cells A. during infection. We identified metabolic pathway that, when inhibited, leads enhanced responses toward bacteria, improving clearance reducing severity disease. The response was...
The mycobacterial ESX-1 virulence locus accelerates macrophage recruitment to the forming tuberculous granuloma. Newly recruited macrophages phagocytose previously infected apoptotic become new bacterial growth niches. Granuloma can then necrose, releasing mycobacteria into extracellular milieu, which potentiates their even further. Using zebrafish with genetic or pharmacologically induced deficiencies, we find that global deficits increase susceptibility infection by accelerating granuloma...
Multisystem inflammatory syndrome in children (MIS-C) is a delayed-onset, COVID-19-related hyperinflammatory illness characterized by severe acute respiratory coronavirus 2 (SARS-CoV-2) antigenemia, cytokine storm, and immune dysregulation. In COVID-19, neutrophil activation central to complications, yet the role of neutrophils MIS-C undefined. Here, we collect blood from 152 children: 31 cases MIS-C, 43 pediatric 78 controls. We find that display granulocytic myeloid-derived suppressor cell...
Microglia, the resident macrophage precursors of brain, are necessary for maintenance tissue homeostasis and activated by a wide range pathological stimuli. They have key role in immune inflammatory responses. Early microglia stem from primitive macrophages, however transition early motile forms to ramified mature has not been assayed real time. In order provide such an assay, we used zebrafish transgenic lines which fluorescent reporter expression is driven promoter expressed gene 1 (mpeg1;...
Oxidative modification of LDL is an early pathological event in the development atherosclerosis. Oxidation events such as malondialdehyde (MDA) formation may produce specific, immunogenic epitopes. Indeed, antibodies to MDA-derived epitopes are widely used atherosclerosis research and have been demonstrated enable cardiovascular imaging. In this study, we engineered a transgenic zebrafish with temperature-inducible expression EGFP-labeled single-chain human monoclonal antibody, IK17, which...
Stimulation of neutrophil reverse migration presents an attractive, alternative therapeutic pathway to driving inflammation resolution. However, little is known about whether the activity wound-experienced neutrophils altered and encouraging dispersal such back into body may have undesirable consequences. This study used a zebrafish tail transection model, in combination with photoconvertible transgenic line, allow internally controlled, simultaneous comparison reverse-migrated naïve...
Neutrophils and macrophages provide the first line of cellular defence against pathogens once physical barriers are breached, but can play very different roles for each specific pathogen. This is particularly so fungal pathogens, which occupy several niches in host. We developed an infection model talaromycosis zebrafish embryos with thermally-dimorphic intracellular pathogen Talaromyces marneffei used it to define neutrophils establishment. system models opportunistic human prevalent...
Human skin models are essential for understanding dermatological diseases and testing new treatment strategies.
Evidence suggests a proinflammatory role of lysophosphatidic acid (LPA) in various pathologic abnormalities, including the central nervous system. Herein, we describe LPA as an important mediator inflammation after spinal cord injury (SCI) zebrafish and mice. Furthermore, novel monoclonal blocking antibody raised against that potently inhibits LPA's effect vitro vivo. This antibody, B3, specifically binds LPA, prevents it from interacting with its complement receptors, blocks effects on...
Invasive aspergillosis (IA), primarily caused by Aspergillus fumigatus, is an opportunistic fungal infection predominantly affecting immunocompromised and neutropenic patients that difficult to treat results in high mortality. Investigations of neutrophil-hypha interaction vitro animal models IA are limited lack temporal spatial control over interactions. This study presents a new approach for studying at single cell resolution time, which revealed evasive behavior triggered with...
Abstract To migrate efficiently to target locations, cells must integrate receptor inputs while maintaining polarity: a distinct front that leads and rear follows. Here we investigate what is necessary overwrite pre-existing front-rear polarity in neutrophil-like HL60 migrating inside straight microfluidic channels. Using subcellular optogenetic activation, show can reorient weakly polarized cells, but the of strongly refractory new inputs. Transient stimulation reveals multi-step...
Megakaryocytes (MKs) are precursors to platelets, the second most abundant cells in peripheral circulation. However, while platelets known participate immune responses and play significant functions during infections, role of MKs within system remains largely unexplored. Histological studies sepsis patients identified increased nucleated CD61 + lungs, staining (likely microthrombi) kidneys, which correlated with development organ dysfunction. Detailed imaging cytometry blood from found...
Monocytes are critical to innate immunity, participating in chemotaxis during tissue injury, infection, and inflammatory conditions. However, the migration dynamics of human monocytes under different guidance cues not well characterized. Here, we developed a microfluidic device profile characteristics chemotactic barotactic while also assessing effects age cytokine stimulation. Human preferentially migrated toward CCL2 gradient through confined microchannels, regardless donor pathway....
Zebrafish (Danio rerio) embryos are increasingly used as a model for studying the function of vertebrate innate immune system in host-pathogen interactions 1. The major cell types system, macrophages and neutrophils, develop during first days embryogenesis prior to maturation lymphocytes that required adaptive responses. ease obtaining large numbers embryos, their accessibility due external development, optical transparency embryonic larval stages, wide range genetic tools, extensive mutant...
A passive pumping, single-cell trapping microarray was developed to monitor volumetric change of multiple, single cells following hypertonic exposure.