A5014523889- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Gut microbiota and health
- IL-33, ST2, and ILC Pathways
- Single-cell and spatial transcriptomics
- Clostridium difficile and Clostridium perfringens research
- Helicobacter pylori-related gastroenterology studies
- Autophagy in Disease and Therapy
- Reproductive System and Pregnancy
- Immune cells in cancer
- Cellular transport and secretion
- Science Education and Perceptions
- Photoreceptor and optogenetics research
- Bacterial Identification and Susceptibility Testing
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune responses and vaccinations
- Biomedical and Engineering Education
- Immune Response and Inflammation
- Gastrointestinal motility and disorders
- Microbial infections and disease research
- Mycobacterium research and diagnosis
- MicroRNA in disease regulation
- Lipid Membrane Structure and Behavior
- Complement system in diseases
- Parasites and Host Interactions
Harvard University
2018-2024
Salk Institute for Biological Studies
2024
New York University
2013-2018
Brigham and Women's Hospital
2018
University of Wisconsin–Madison
2011
Howard Hughes Medical Institute
2011
Parasitic worms affect gut microbes Improved hygiene practices in high-income countries may come with an increased risk of developing inflammatory bowel disease (IBD) or other similar disorders. Ramanan et al. show that intestinal helminth infection, caused by parasitic worms, protects IBD-susceptible mice from the disease. The infection increases specific protective species and limits members microbiota. People helminth-endemic regions harbored a microbiota, their deworming led to increase...
Abstract Neutrophils are implicated in multiple homeostatic and pathological processes, but whether functional diversity requires discrete neutrophil subsets is not known. Here, we apply single-cell RNA sequencing to neutrophils from normal inflamed mouse tissues. Whereas conventional clustering yields alternative organizational structures, diffusion mapping plus velocity discloses a single developmental spectrum, ordered chronologically. Termed here neutrotime, this spectrum extends...
Different tissue microenvironments differentially refine T reg cell transcriptional regulatory modules already primed in lymphoid organs.
Polymorphisms in the essential autophagy gene Atg16L1 have been linked with susceptibility to Crohn's disease, a major type of inflammatory bowel disease (IBD). Although inability control intestinal bacteria is thought underlie IBD, role during extracellular bacterial infections has not sufficiently examined and compared function other IBD genes, such as Nod2, which encodes cytosolic sensor. We find that mutant mice are resistant induced by model pathogen Citrobacter rodentium. An deficiency...
Many cells release multiple substances in different proportions according to the specific character of a stimulus. PC12 cells, model neuroendocrine cell line, express isoforms exocytotic Ca(2+) sensor synaptotagmin. We show that these sort populations dense-core vesicles differ size. These synaptotagmins their sensitivities, preference for full fusion or kiss-and-run, and sensitivity inhibition by synaptotagmin IV. In harbor can be preferentially triggered fuse forms stimulation. The mode is...
ABSTRACT FoxP3+CD4+ regulatory T cells (Tregs), essential for immunologic and organismal homeostasis, have diverse functions corresponding gene expression programs. How the many controlling transcription factors (TFs) organize to determine Treg identity diversity remains unclear. We combined single-cell chromatin accessibility profiling, machine learning, high-density natural genetic variation, validated with TF knockout, CRISPR-editing, binding data, define network. Distal enhancers proved...
Foxp3 + regulatory T cells (Tregs) in the colon are key to promoting peaceful coexistence with symbiotic microbes. Differentiated either thymic or peripheral locations, and modulated by microbes other cellular influencers, colonic Treg subsets have been identified through transcription factors (TFs; Helios, Rorγ, Gata3, cMaf), but their interrelationships unclear. Applying a multimodal array of immunologic, genomic, microbiological assays, we find more overlap than expected between...
T cells that express the transcription factor RORγ, regulatory (Treg), or conventional (Th17) are strongly influenced by intestinal symbionts. In a genetic approach to identify mechanisms underlying this influence, we performed screen for microbial genes implicated, in germfree mice monocolonized with Escherichia coli Nissle. The loss of capsule-synthesis impaired clonal expansion and differentiation RORγ + cells. Mechanistic exploration revealed capsule-less mutants remained able induce...
Phenotypic differences among substrains of laboratory mice due to spontaneous mutations or pre-existing genetic variation confound the interpretation targeted mutagenesis experiments and contribute challenges with reproducibility across institutions. Notably, C57BL/6 Hsd gene-targeted that have been backcrossed this substrain reported harbor a duplication in exons 28 29
Foxp3 + regulatory T cells (Tregs) in the colon are key to promoting peaceful co-existence with symbiotic microbes. Differentiated either thymic or peripheral locations, and modulated by microbes other cellular influencers, colonic Treg subsets have been identified through transcription factors (TF; Helios, Rorg, Gata3, cMaf), but their inter-relationships unclear. Applying a multimodal array of immunologic, genomic, microbiological assays, we find more overlap than expected between...
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...
Abstract Canonically, complement is a serum-based host defense system that protects against systemic microbial invasion. Little known about the production and function of components on mucosal surfaces. Here we show gut component 3 (C3), central to function, regulated by composition microbiota in healthy humans mice, leading host-specific C3 levels. Stromal cells intestinal lymphoid follicles (LFs) are predominant source C3. During enteric infection with Citrobacter rodentium or...
ABSTRACT Phenotypic differences among substrains of laboratory mice due to spontaneous mutations or pre-existing genetic variation confound the interpretation targeted mutagenesis experiments, and contribute challenges with reproducibility across institutions. Notably, C57BL/6NHsd gene-targeted that have been backcrossed this substrain reported harbor a duplication in exons 28 29 Dock2 . Here, we demonstrate presence variant widely used Nod2 −/− mice. NOD2 is cytosolic innate immune receptor...