A5031000571- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- Developmental Biology and Gene Regulation
- Tuberculosis Research and Epidemiology
- Immunodeficiency and Autoimmune Disorders
- Mycobacterium research and diagnosis
- Single-cell and spatial transcriptomics
- CAR-T cell therapy research
- Epigenetics and DNA Methylation
- Diabetes and associated disorders
- Immune Response and Inflammation
Columbia University
2021-2024
Columbia University Irving Medical Center
2018-2022
University of Glasgow
2018-2019
University of Oxford
2019
National Institute of Immunology
2014-2018
Stanford University
1999
Bacille Calmette-Guérin (BCG) vaccines are live attenuated strains of Mycobacterium bovis administered to prevent tuberculosis. To better understand the differences between M. tuberculosis , and various BCG daughter strains, their genomic compositions were studied by performing comparative hybridization experiments on a DNA microarray. Regions deleted from relative virulent H37Rv reference strain confirmed sequencing across missing segment genome. Eleven regions (encompassing 91 open...
Abstract Sustained Notch2 signals induce trans-differentiation of Follicular B (FoB) cells into Marginal Zone (MZB) in mice, but the physiology underlying this differentiation pathway is still elusive. Here, we demonstrate that most receive a basal Notch signal, which intensified pre-MZB and MZB cells. Ablation or constitutive activation upon T-cell-dependent immunization reveals an interplay between antigen-induced signaling, FoB turn off signaling enter germinal centers (GC), while high...
Thymic involution and proliferation of naive T cells both contribute to shaping the T-cell repertoire as humans age, but a clear understanding roles each throughout human life span has been difficult determine. By measuring nuclear bomb test-derived 14C in genomic DNA, we determined turnover rates CD4+ CD8+ populations defined their dynamics healthy individuals ranging from 20 65 years age. We demonstrate that generation decreases with age because combination declining peripheral division...
The processes regulating peripheral naive T-cell numbers and clonal diversity remain poorly understood. Conceptually, homeostatic mechanisms must fall into the broad categories of neutral (simple random birth–death models), competition (regulation cell through quorum-sensing, perhaps via limiting shared resources), adaptation (involving cell-intrinsic changes in fitness, defined as net growth rate over time), or selection loss outgrowth populations deriving from intercellular variation...
Naive CD4 and CD8 T cells are cornerstones of adaptive immunity, but the dynamics their establishment early in life how kinetics change as they mature following release from thymus poorly understood. Further, due to diverse signals implicated naive cell survival, it has been a long-held conceptually attractive view that sustained by active homeostatic control thymic activity wanes. Here we use multiple modelling experimental approaches identify unified model population mice, across lifespan....
Follicular mature (FM) and germinal center (GC) B cells underpin humoral immunity, but the dynamics of their generation maintenance are not clearly defined. Here, we exploited a fate-mapping system in mice that tracks as they develop into peripheral subsets, together with cell division fate reporter mouse mathematical models. We find FM kinetically homogeneous, recirculate freely, continually replenished from transitional populations, self-renew rarely. In contrast, GC lineages persist for...
Initiation of adaptive immunity involves distinct migratory cell populations coming together in a highly dynamic and spatially organised process. However, we lack detailed spatiotemporal map these events due to our inability track the fate cells between anatomically locations or functionally identify as migratory. We used photo-convertible transgenic mice (Kaede) spatiotemporally composition that leave site priming enter draining lymph node initiate immunity. show following skin priming,...
ABSTRACT Thymic involution and proliferation of naive T cells both contribute to shaping the cell repertoire as humans age, but a clear understanding roles each throughout human lifespan has been difficult determine. By measuring nuclear bomb test-derived 14 C in genomic DNA we determined turnover rates CD4 + CD8 naïve populations defined their dynamics healthy individuals ranging from 20-65 years age. We demonstrate that generation decreases with this could be explained by combination...
As individual naïve CD4 T lymphocytes circulate in the body after emerging from thymus, they are likely to have individually varying microenvironmental interactions even absence of stimulation via specific target recognition. It is not clear if these result alterations their activation, survival and effector programming. Naïve cells show unimodal distribution for many phenotypic properties, suggesting that variation caused by intrinsic stochasticity, although underlying due subsets created...
Abstract We have previously demonstrated co‐receptor level‐associated functional heterogeneity in apparently homogeneous naive peripheral CD 4 T cells, dependent on MHC ‐mediated tonic signals. Maturation pathways can differ between and 8 so we tested whether the latter showed similar heterogeneity. report that, when either polyclonal T‐cell receptor ( TCR )‐transgenic monoclonal cells from young mice were separated into hi lo subsets, responded poorly, but subsets of single‐positive SP )...
Abstract Foxp3 + Regulatory T cells (Treg) are a subset of CD4 that play critical functions in maintaining tolerance to self antigens and suppressing autoimmunity, regulating immune responses pathogens have role the pathophysiology anti-tumoural immunity. Treg ontogeny is complex since they generated following recognition thymus during normal cell development (thymic Treg), but also induced from mature conventional when activated by foreign antigen with appropriate additional cues (inducible...
Abstract Variability in cellular activation the immune system can have diverse consequences, resulting heterogeneity effector programming and function as well cell survival. While examining relationships between lymphocyte functionality, we find that apparently unimodally distributed coreceptor among naive T cells, simplistically expected to be due intrinsic noise, is not only correlated with major functional variation but modulated by extrinsic microenvironmental cues vivo. Thus, when cells...
Summary Follicular mature (FM) and germinal centre (GC) B cells underpin humoral immunity but the dynamics of their generation maintenance are not clearly defined. Here we exploited a fate-mapping system in mice that tracks as they develop into peripheral subsets, together with cell division fate reporter mouse mathematical models. We find FM kinetically homogeneous, recirculate freely, continually replenished from transitional populations, self-renew rarely. In contrast, GC lineages persist...
Abstract Naive CD4 and CD8 T cells are cornerstones of adaptive immunity, but the dynamics their establishment early in life how kinetics change as they mature following release from thymus poorly understood. Further, due to diverse signals implicated naive cell survival, it has been a long-held conceptually attractive view that sustained by active homeostatic control thymic activity wanes. Here we employ multiple experimental systems identify unified model population across mouse lifespan....
Abstract Notch2 signaling has a profound role in driving the development of Marginal Zone B (MZB) cells. We recently demonstrated that Follicular (FoB) cells act as precursors for MZB mice, but mechanistic aspects this differentiation pathway are still elusive. By studying Notch CBF:H2B-Venus Notch-reporter we show most receive signal, which is highest However, surprisingly, around one-third seem to lose their signal with time. Conditional deletion or constitutive activation mice upon...