A5064802443- Immune Cell Function and Interaction
- SARS-CoV-2 and COVID-19 Research
- T-cell and B-cell Immunology
- IL-33, ST2, and ILC Pathways
- COVID-19 Clinical Research Studies
- Immune Response and Inflammation
- Long-Term Effects of COVID-19
- Single-cell and spatial transcriptomics
- Molecular Biology Techniques and Applications
- Metabolomics and Mass Spectrometry Studies
- Stress Responses and Cortisol
- Sphingolipid Metabolism and Signaling
- Biopolymer Synthesis and Applications
- Chemical Synthesis and Analysis
- Inflammasome and immune disorders
- Neuropeptides and Animal Physiology
- Gut microbiota and health
- Viral gastroenteritis research and epidemiology
- Peroxisome Proliferator-Activated Receptors
- RNA Interference and Gene Delivery
- Orthopedic Infections and Treatments
- Diabetes and associated disorders
- Gastrointestinal motility and disorders
- Advanced Chemical Sensor Technologies
- Viral Infections and Outbreaks Research
Harvard University
2020-2024
Boston VA Research Institute
2021-2024
Brigham and Women's Hospital
2023
Trinity College Dublin
2015-2019
GlaxoSmithKline (United Kingdom)
2017-2018
Abstract Macrophages undergo metabolic changes during activation that are coupled to functional responses. The gram negative bacterial product lipopolysaccharide (LPS) is especially potent at driving reprogramming, enhancing glycolysis and altering the Krebs cycle. Here we describe a role for citrate-derived metabolite malonyl-CoA in effect of LPS macrophages. Malonylation wide variety proteins occurs response LPS. We focused on one these, glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In...
The hallmark of severe COVID-19 is an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. We hypothesized that perturbations in FoxP3+ T regulatory cells (Treg), key enforcers immune homeostasis, contribute to pathology. Cytometric and transcriptomic profiling revealed a distinct Treg phenotype patients, with increase proportions intracellular levels the lineage-defining transcription factor FoxP3, correlating poor outcomes. These Tregs showed...
Neuroimmune cross-talk participates in intestinal tissue homeostasis and host defense. However, the matrix of interactions between arrays molecularly defined neuron subsets immunocyte lineages remains unclear. We used a chemogenetic approach to activate eight distinct neuronal subsets, assessing effects by deep immunophenotyping, microbiome profiling, transcriptomics organs. Distinct immune perturbations followed activation: Nitrergic neurons regulated T helper 17 (T
Dysbiosis in the gut microbiota affects several systemic diseases, possibly by driving migration of perturbed intestinal immunocytes to extraintestinal tissues. Combining Kaede photoconvertible mice and single-cell genomics, we generated a detailed map migratory trajectories from colon, at baseline, models inflammation. All lineages emigrated colon an S1P-dependent manner. B lymphocytes represented largest contingent, with unexpected circulation nonexperienced follicular cells, which carried...
Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) provokes a potentially fatal pneumonia with multiorgan failure, and high systemic inflammation. To gain mechanistic insight ferret out the root of this immune dysregulation, we modeled, in vitro coculture, interactions between infected epithelial cells immunocytes. A strong response was induced monocytes B cells, SARS-CoV-2-specific inflammatory gene cluster distinct from that seen influenza or Ebola virus-infected...
The hallmark of severe COVID-19 disease has been an uncontrolled inflammatory response, resulting from poorly understood immunological dysfunction. We explored the hypothesis that perturbations in FoxP3+ T regulatory cells (Treg), key enforcers immune homeostasis, contribute to pathology. Cytometric and transcriptomic profiling revealed a distinct Treg phenotype patients, with increase both proportions intracellular levels lineage-defining transcription factor FoxP3, which correlated poor...
Technologies that facilitate the bulk sequencing of small numbers cells as well single-cell RNA (scRNA-seq) have aided greatly in study viruses these analyses can be used to differentiate responses from infected versus bystander complex systems, including organoid or animal studies. While protocols for are typically developed with biosafety level 2 (BSL-2) considerations mind, such equally useful require higher containment levels. Many workstreams, however, not directly compatible more...
Pregnancy brings about profound changes to the mammary gland in preparation for lactation. Changes immunocyte populations that accompany this rapid remodeling are incompletely understood. We comprehensively analyzed T cells through all parous stages, revealing a marked increase CD4+ and CD8+ effector late pregnancy cell expansion was partly dependent on microbial signals included an TCRαβ+CD8αα+ with strong cytotoxic markers, located epithelium, resemble intraepithelial lymphocytes of...
SUMMARY Dysbiosis in the gut microbiota impacts several systemic diseases. One possible mechanism is migration of perturbed intestinal immunocytes to extra-intestinal tissues. Combining Kaede photoconvertible mouse model and single-cell genomics, we generated a detailed map migratory trajectories from colon, at baseline during inflammation. All colonic lineages emigrated colon an S1P-dependent manner, dominated by B lymphocytes with large continuous circulation follicular cells, which...
Malonylation is a recently uncovered protein post-translational modification. It involves the attachment of malonyl group to lysines, resulting in an extra 86 Da mass, as well change charge comparable that phosphorylation. The enzyme responsible for malonylation has not yet been uncovered, but it seems like levels are dependent on malonyl-CoA concentration. discovery this new modification took place during time which immunometabolism became emerging field and many studies into metabolism...
ABSTRACT Infection by SARS-CoV2 provokes a potentially fatal pneumonia with multiorgan failure, and high systemic inflammation. To gain mechanistic insight ferret out the root of this immune dysregulation, we modeled in vitro co-culture interactions between infected epithelial cells immunocytes. A strong response was induced monocytes B cells, SARS-CoV2-specific inflammatory gene cluster distinct from that seen influenza-A or Ebola virus-infected co-cultures, which reproduced deviations...