A5015428250- T-cell and B-cell Immunology
- Ocular Diseases and Behçet’s Syndrome
- Systemic Lupus Erythematosus Research
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Single-cell and spatial transcriptomics
- Immune cells in cancer
- Extracellular vesicles in disease
- Monoclonal and Polyclonal Antibodies Research
- Sarcoidosis and Beryllium Toxicity Research
- Inflammasome and immune disorders
- IL-33, ST2, and ILC Pathways
- Proteoglycans and glycosaminoglycans research
- Phagocytosis and Immune Regulation
- Chronic Lymphocytic Leukemia Research
- interferon and immune responses
- Cancer Research and Treatments
- Glycosylation and Glycoproteins Research
- Immune Response and Inflammation
- Autoimmune and Inflammatory Disorders
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- CAR-T cell therapy research
- Reproductive System and Pregnancy
- Telomeres, Telomerase, and Senescence
Brigham and Women's Hospital
2017-2023
Harvard University
2017-2023
BioNTech (United States)
2021
Broad Institute
2018-2019
National Institutes of Health
2014-2016
National Eye Institute
2014-2016
Foundation for the National Institutes of Health
2015
Carnegie Mellon University
2013
Abstract How innate T cells (ITC), including invariant natural killer (iNKT) cells, mucosal-associated (MAIT) and γδ maintain a poised effector state has been unclear. Here we address this question using low-input single-cell RNA-seq of human lymphocyte populations. Unbiased transcriptomic analyses uncover continuous ‘innateness gradient’, with adaptive at one end, followed by MAIT, iNKT, the other end. Single-cell reveals four broad states innateness, heterogeneity within canonical...
High-dimensional single-cell analyses have improved the ability to resolve complex mixtures of cells from human disease samples; however, identifying disease-associated cell types or states in patient samples remains challenging because technical and interindividual variation. Here, we present mixed-effects modeling associations single (MASC), a reverse association strategy for testing whether case-control status influences membership any multiple cellular subsets while accounting...
Purpose: Extracellular vesicles (EV), such as exosomes, are important mediators of intercellular communication and have been implicated in modulation the immune system. We investigated if EV released from retinal pigment epithelium (RPE) modulate responses vitro. Methods: were isolated ARPE-19 cultures stimulated or not with inflammatory cytokines IL-1β, IFN-γ, TNF-α. Isolated characterized by nanoparticle flow Western blot analyses. Retinal epithelium–derived cultured human peripheral blood...
Human peripheral monocytes have been categorized into three subsets based on differential expression levels of CD14 and CD16. However, the factors that influence distribution monocyte roles each subset plays in autoimmunity are not well studied. In this study, we show circulating from patients with autoimmune uveitis exhibit a skewed phenotype toward intermediate CD14(++)CD16(+) cells, is associated glucocorticoid therapy. We further demonstrate healthy control donors share similar...
Despite the report of an imbalance between CD4+ T helper (Th) cell subsets in rheumatoid arthritis (RA), patient stratification for precision medicine has been hindered by discovery ever more Th subsets, as well contradictory association results.To capture previously reported RA with deep immunophenotyping techniques; to compare hypothesis-free unsupervised automated clustering hypothesis-driven conventional biaxial gating and explore if heterogeneity accounts conflicting...
Sarcoidosis is a chronic inflammatory disease with systemic granulomatous disorder affecting multiple organs including the eye. Both CD4+ T cell and macrophage have been linked to pathogenesis of disease. The expression IL-17RC was measured using FACS,immunohistochemistry real-time PCR. Serum level IL-17 detected ELISA. An elevated on CD8+ cells in peripheral blood found patients ocular sarcoidosis as compared healthy controls. Interestingly, we significant increase serum controls, which may...
Purpose.: Myeloid dendritic cells (mDCs) play an important role in autoimmune diseases. However, the of blood CD1c+ myeloid 1 (mDC1s), subset human mDCs, is not well understood noninfectious uveitis. Methods.: Fresh peripheral samples from uveitis patients (n = 32) and healthy controls (HCs) 64) were stained with FITC-Lineage (Lin1), PERCP-HLADR, PE-CD1c antibodies. The levels mDC1 quantified by using flow cytometric analysis. Longitudinal data 16) analyzed to correlate disease activity....
Purpose: To test the association between elevated proportions of CD1c+ myeloid dendritic cells (mDCs) and disease activation/reactivation in noninfectious uveitis. Methods: Noninfectious uveitis patients (n = 89) healthy controls 111) were recruited. The proportion mDCs total cell (DC) population peripheral blood was measured by flow cytometry (CD1c+ gated on Lineage 1+HLADR+ DCs). Disease activity assessed per Standardization Uveitis Nomenclature criteria. reactivation ascribed to...
Abstract Understanding how genetic regulatory variation affects gene expression in different T cell states is essential to deciphering autoimmunity. We conducted a high-resolution RNA-seq time course analysis of stimulated memory CD4 + cells from 24 healthy individuals. identified 186 genes with dynamic allele-specific expression, where the balance alleles changes over time. These were four fold enriched autoimmune loci. found pervasive effects within six HLA genes, particularly for major...
A bstract High dimensional single-cell analyses have dramatically improved the ability to resolve complex mixtures of cells from human disease samples; however, identifying disease-associated cell types or states in patient samples remains challenging due technical and inter-individual variation. Here we present Mixed effects modeling Associations Single Cells (MASC), a novel reverse single association strategy for testing whether case-control status influences membership any multiple...
Abstract Innate T cells (ITCs), including invariant natural killer (iNKT) cells, mucosal-associated (MAIT) and γδ cell populations, use conserved antigen receptors generated by somatic recombination to respond non-peptide antigens in an innate-like manner. Understanding where these fit the scheme of immunity has been a puzzle since their discovery. Here, immunophenotyping 101 individuals revealed that populations account for as much 25% peripheral human cells. To better understand we...
Abstract Our longitudinal data has shown that the level of CD1c+ myeloid dendritic cells 1 (mDC1) from peripheral blood reflects disease activity in autoimmune non-infectious uveitis patients. However, role mDC1 is not clear Here, we demonstrate patients with (n=74) was increased compared to age and gender-matched healthy controls (n=96). The exhibited high HLADR expression less antigen uptake. were further divided into two subpopulations based on CD1c expression. CD1chi subpopulation showed...
<h3>Background</h3> Neoantigens are tumor-specific antigens that important in the anti-tumor immune response. These not subject to central tolerance and therefore potentially more immunogenic than tumor-associated antigens. Here, we present results of a proof-of-concept, pre-clinical study with multiple successful patient material runs generating neoantigen-specific T-cell product (BNT221/NEO-PTC-01) using leukaphereses from patients ovarian cancer. products contain specific responses...