A5034346446- Antifungal resistance and susceptibility
- Fungal Infections and Studies
- Autophagy in Disease and Therapy
- Microfluidic and Bio-sensing Technologies
- Advanced biosensing and bioanalysis techniques
- Studies on Chitinases and Chitosanases
- SARS-CoV-2 detection and testing
- Immune Response and Inflammation
- Immunotherapy and Immune Responses
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Orbital Angular Momentum in Optics
- Cell Adhesion Molecules Research
- Cytomegalovirus and herpesvirus research
- Polysaccharides and Plant Cell Walls
- Advanced Fluorescence Microscopy Techniques
- Cancer-related molecular mechanisms research
- interferon and immune responses
- Escherichia coli research studies
- Gut microbiota and health
- Plant-Microbe Interactions and Immunity
- Respiratory viral infections research
- Immune Cell Function and Interaction
- Vibrio bacteria research studies
- Biosensors and Analytical Detection
- Carbohydrate Chemistry and Synthesis
Harvard University
2013-2024
Wyss Institute for Biologically Inspired Engineering
2023
Boston VA Research Institute
2021-2022
Inspire
2021
Massachusetts General Hospital
2011-2020
Office of Infectious Diseases
2013-2014
In-Q-Tel
2011
Harvard University Press
2009
Tufts University
2003-2008
Gordon Center for Medical Imaging
2007
Incorporating TLR9-inhibitory sequences in the AAV vector genome inhibits immunogenicity and enhances transgene expression multiple animal models.
Filamentous fungi drive carbon and nutrient cycling across our global ecosystems, through its interactions with growing decaying flora their constituent microbiomes. The remarkable metabolic diversity, secretion ability, fiber-like mycelial structure that have evolved in filamentous been increasingly exploited commercial operations. industrial potential of fermentation ranges from the discovery bioproduction enzymes bioactive compounds, decarbonization food material production, to...
Autophagy has been postulated to play role in mammalian host defense against fungal pathogens, although the molecular details remain unclear. Here, we show that primary macrophages deficient autophagic factor LC3 demonstrate diminished fungicidal activity but increased cytokine production response Candida albicans stimulation. recruitment phagosomes requires activation of pattern receptor dectin-1. phagosome also Syk signaling is independent all by Toll-like receptors and does not require...
Elimination of fungal pathogens by phagocytes requires phagosome maturation, a process that involves the recruitment and fusion intracellular proteins. The role Dectin-1, β-1,3-glucan receptor, critical for recognition triggering Th17 responses, to phagosomal maturation has not been defined. We show GFP-Dectin-1 translocates phagosome, but its signal decays after 2 h. Inhibition acidification results in retention membranes highlighting requirement an acidic pH. Following recognition,...
Abstract We present barcoded oligonucleotides ligated on RNA amplified for multiplexed and parallel insitu analyses (BOLORAMIS), a reverse transcription-free method spatially-resolved, targeted, in situ identification of single or multiple targets. BOLORAMIS was demonstrated range cell types human cerebral organoids. Singleplex experiments to detect coding non-coding RNAs iPSCs showed stem-cell signature pattern. Specificity found be 92% as illustrated by clear distinction between mouse...
In BriefAlthough genome-wide association studies are valuable in identifying disease-associated loci, they produce only a partial view of pathogenesis.Using integrated, systems-level approaches to pinpoint genes that interact with the Crohn's-disease-associated variant ATG16L1 T300A, Begun et al. identify CLEC12A as an innate defense gene functions antibacterial autophagy.
Abstract Integrin signalling triggers cytoskeletal rearrangements, including endocytosis and exocytosis of integrins other membrane proteins. In addition to recycling integrins, this trafficking can also regulate intracellular pathways. Here we describe a role for αv in regulating Toll-like receptor (TLR) by modulating trafficking. We show that deletion or β3 causes increased B-cell responses TLR stimulation vitro , αv-conditional knockout mice have elevated antibody TLR-ligand-associated...
Bipolar disorder (BD) is a severe psychiatric condition marked by episodes of mania and depression, with neurotransmitter imbalance in the midbrain believed to play critical role its pathophysiology. Despite this, there currently no validated model for examining BD-associated molecular changes available. Leveraging recent advances stem cell technology, we developed organoid using human induced pluripotent cells (hiPSCs) from BD patients healthy controls (CTR). To address issues variability...
Phagocytic responses are critical for effective host defense against opportunistic fungal pathogens. Macrophages sample the phagosomal content and orchestrate innate immune response. Toll-like receptor 9 (TLR9) recognizes unmethylated CpG DNA is activated by DNA. Here we demonstrate that specific triggering of TLR9 recruitment to macrophage membrane a conserved feature fungi distinct phylogenetic origins, including Candida albicans, Saccharomyces cerevisiae, Malassezia furfur, Cryptococcus...
Abstract Dectin-1 and TLR9 play distinct roles in the recognition induction of innate immune responses to Aspergillus fumigatus Candida albicans. is a receptor for major fungal cell wall carbohydrate β-1,3 glucan that induces inflammatory cytokines controls phagosomal maturation through spleen tyrosine kinase activation. an endosomal TLR also modulates cytokine response pathogens. In this study, we demonstrate beads are sufficient induce dynamic redistribution accumulation cleaved...
Tetraspanins are a family of proteins possessing four transmembrane domains that help in lateral organization plasma membrane proteins. These interact with each other as well receptors and signaling proteins, resulting functional complexes called "tetraspanin microdomains." Tetraspanins, including CD82, play an essential role the pathogenesis fungal infections. Dectin-1, receptor for cell wall carbohydrate β-1,3-glucan, is vital to host defense against The current study identifies novel...
Journal Article Use of fungal derived polysaccharide-conjugated particles to probe Dectin-1 responses in innate immunity Get access Jenny M. Tam, Tam Department Medicine, Division Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, GRJ-5-504, Boston, MA 02114, USA. Fax: +1 617 643 6443; Tel: 6444 Search for other works by this author on: Oxford Academic Google Scholar Michael K. Mansour, Mansour Nida S. Khan, Khan Nicholas C. Yoder, Yoder Whitehead...
Abstract The C-type lectin receptor dectin-1 and the integrin Mac-1 have key roles in controlling fungal infection. Here, we demonstrate that dectin-1- Mac-1-induced activation of protein kinase Cδ neutrophils, independent Card9 adaptor, is required for reactive oxygen species production intracellular killing upon Candida albicans uptake. Protein was also zymosan-induced cytokine generation neutrophils. In macrophages, deficiency prevented fungi-induced but had no effect on TGF-β-activated...
An array of electrode tips with 6-microm center-to-center spacing, fabricated through chemical etching an optical fiber bundle, and coated gold, was used for initiating electrochemiluminescence (ECL) in aqueous solution Ru(bpy)3(2+) tri-n-propylamine (TPrA). ECL generated at the electrodes detected a CCD camera exhibited both high sensitivity resolution. In case which signal could not be distinguished from background, signals obtained by pulsing summing multiple images. The behavior this...
In this letter, we present a method to generate and regenerate arrays of microspheres by optically trapping through optical imaging fiber bundles. method, laser beam is coupled into the proximal end an bundle, light energy distributed across face fiber. Each illuminated individual in array propagates distal where focusing elements at each focus form traps. These traps are capable capturing arraying parallel. The number determined fibers bundle creating dense (∼5×104 traps/mm2) tweezers.
Beyond its well-documented role in reproduction, embryogenesis and maintenance of body tissues, vitamin A has attracted considerable attention due to immunomodulatory effects on both the innate adaptive immune responses. In infectious diseases, been shown have a host-protective effect infections bacterial, viral or protozoan origin. Nevertheless, impact fungal remains unknown. Meanwhile, frequency invasive mycoses keeps growing, with Candida albicans being major opportunistic pathogen...
The tetraspanin CD82 is a potent suppressor of tumor metastasis and regulates several processes including signal transduction, cell adhesion, motility, aggregation. However, the mechanisms by which participates in innate immunity are unknown. We report that key regulator TLR9 trafficking signaling. recognizes unmethylated cytosine-phosphate-guanine (CpG) motifs present viral, bacterial, fungal DNA. demonstrate associate macrophages, occurs endoplasmic reticulum (ER) post-ER. Moreover,...
The mechanism of protection against cholera afforded by previous illness or vaccination is currently unknown. We have recently shown that antibodies targeting O-specific polysaccharide (OSP) Vibrio cholerae correlate highly with cholera. V. motile and possesses a flagellum sheathed in OSP, motility correlates virulence. Using high-speed video microscopy building upon animal-related work, we demonstrate sera, polyclonal antibody fractions, OSP-specific monoclonal recovered from humans...
Green fluorescent protein (GFP) has been used for cell tracking and imaging gene expression in superficial or surgically exposed structures. However, vivo murine is often limited by several factors, including scatter attenuation with depth overlapping autofluorescence. The autofluorescence signals have spectral profiles that are markedly different from the GFP emission profile. use of allows separation quantitation these contributions to total fluorescence signal seen weighting known pure...
The application of live cell imaging allows direct visualization the dynamic interactions between cells immune system. Some preliminary observations challenge long-held beliefs about responses to microorganisms; however, lack spatial and temporal control phagocytic microbe has rendered focused into initial host response pathogens difficult. This paper outlines a method that advances by integrating spinning disk confocal microscope with an optical trap, also known as tweezer, in order provide...