A5020536875- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- HIV Research and Treatment
- HIV/AIDS Research and Interventions
- Immune responses and vaccinations
- COVID-19 epidemiological studies
- vaccines and immunoinformatics approaches
- Single-cell and spatial transcriptomics
- Mathematical and Theoretical Epidemiology and Ecology Models
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune Response and Inflammation
- HIV/AIDS drug development and treatment
- Energy, Environment, and Transportation Policies
- HIV-related health complications and treatments
- Monoclonal and Polyclonal Antibodies Research
- Lymphoma Diagnosis and Treatment
- Electric Vehicles and Infrastructure
- Statistical Methods and Bayesian Inference
- Air Quality and Health Impacts
- COVID-19 impact on air quality
- Energy and Environment Impacts
- Evolution and Genetic Dynamics
- CAR-T cell therapy research
- Hematopoietic Stem Cell Transplantation
Columbia University Irving Medical Center
2017-2025
University of Amsterdam
2024
University of North Carolina at Chapel Hill
2020-2024
Columbia University
2018-2021
University of North Carolina at Greensboro
2020
National Bureau of Economic Research
2020
University of Chicago
2020
Carnegie Mellon University
2020
Dartmouth College
2020
Royal North Shore Hospital
2020
Why do parasites harm their hosts? Conventional wisdom holds that because depend on hosts for survival and transmission, they should evolve to become benign, yet many cause harm. Theory predicts could virulence (i.e., parasite-induced reductions in host fitness) by balancing the transmission benefits of parasite replication with costs death. This idea has led researchers predict how human interventions-such as vaccines-may alter evolution, empirical support is critically lacking. We studied...
Naïve T cells continually recirculate between blood and secondary lymphoid organs, scanning dendritic (DC) for foreign antigen. Despite its importance understanding how adaptive immune responses are efficiently initiated from rare precursors, a detailed quantitative analysis of this fundamental process has not been reported. Here we measure lymph node (LN) entry, transit, exit rates naïve CD4 + CD8 cells, then use intravital imaging mathematical modeling to relate cell–cell interaction...
Abstract Background The first step in invasive disease caused by the normally commensal bacteria Streptococcus pneumoniae , Staphylococcus aureus and Haemophilus influenzae is their colonization of nasal passages. For any population to colonize a new habitat it necessary for be able compete with existing organisms evade predation. In case these species competition between strains same different predation mediated host's immune response. Here, we use neonatal rat model explore elements...
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...
Abstract Understanding T cell homeostasis requires knowledge of the export rate new cells from thymus, a that has been surprisingly difficult to estimate. TCR excision circle (TREC) content used as proxy for thymic export, but this quantity is influenced by division and loss naive not direct measure export. We present in study method quantifying humans combining two simple mathematical models. One uses Ki67 data calculate peripheral production, whereas other tracks dynamics TRECs. Combining...
It has long been recognized that the T-cell compartment more CD4 helper than CD8 cytotoxic T cells, and this is most evident looking at development in thymus. However, it remains unknown how thymocyte so favors lineage development. To identify basis of asymmetry, we analyzed synchronized cohorts thymocytes vivo estimated rates death differentiation throughout development, inferring lineage-specific efficiencies selection. Our analysis suggested roughly equal numbers cells each enter...
A diverse array of T cells is required for defense against pathogens. The naive CD4 T-cell repertoire reaches its peak diversity by early human adulthood and maintained until older age. Surprisingly, around age 70, this appears to plummet abruptly. similar qualitative pattern holds the memory-cell population. We used mathematical models explore different hypotheses how such a loss might occur. prevailing suggest that due decline in emigration from thymus or contraction total number cells....
Characterising the longevity of immunological memory requires establishing rules underlying renewal and death peripheral T cells. However, we lack knowledge population structure how self-renewal de novo influx contribute to maintenance compartments. Here, characterise kinetics murine CD4 cell subsets by measuring rates new cells using detailed timecourses DNA labelling that also distinguish behaviour recently divided quiescent We find both effector central comprise subpopulations with highly...
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...
In two studies, we examined people's level of risk taking when making monetary decisions for other people rather than themselves. Experiment 1 the role regret in these situations; results show that concerns led to increased avoidance both participants made as well 2 tested whether skill tasks would lead greater decision was another person versus oneself. This hypothesis not supported, although men were more seeking women situations. Taken together, studies suggest many findings from research...
Heterogeneity in the parameters governing spread of infectious diseases is a common feature real-world epidemics. It has been suggested that for pathogens with basic reproductive number R 0 >1, increasing heterogeneity makes extinction disease more likely during early rounds transmission. The introduced pathogen may, however, be less than 1 after introduction, and evolutionary changes are then required to increase above emerge. In this paper, we consider how host influences emergence both...
Significance T cells are essential components of vertebrate immune systems, but the mechanisms by which they maintained still poorly defined. Existing methods infer cell lifetimes and division rates using DNA labeling dividing cells, do not resolve heterogeneity in population dynamics well. We present a novel experimental system that, when combined with mathematical models, yields kinetic parameters allows us to measure effect cell’s age on its ability survive divide. Our approach quantifies...
A dense population of embryo-derived Langerhans cells (eLCs) is maintained within the sealed epidermis without contribution from circulating cells. When this network perturbed by transient exposure to ultraviolet light, short-term LCs are temporarily reconstituted an initial wave monocytes but thought be superseded more permanent repopulation with undefined LC precursors. However, extent which process relevant immunopathological processes that damage integrity not known. Using a model...
What determines the dynamics of parasite and anaemia during acute primary malaria infections? Why do some strains reach higher densities cause greater than others? The conventional view is that fastest replicating parasites highest greatest loss red blood cells (RBCs). Other current hypotheses suggest maximum density achieved by either elicit weakest immune responses or infect youngest RBCs (reticulocytes). Yet another hypothesis a simple resource limitation model where peak (percentage...
Background The asymptomatic phase of HIV infection is characterised by a slow decline peripheral blood CD4+ T cells. Why this not understood. One potential explanation that the low average rate homeostatic proliferation or immune activation dictates pace “runaway” memory cells, in which drives infection, higher viral loads, more recruitment cells into an activated state, and further events. We explore hypothesis using mathematical models. Methods Findings Using simple models dynamics cell...
Poor immunological responders (PIR) are HIV-infected patients with virologic suppression upon antiretroviral therapy (ART) but persistently low CD4+ T cell counts. Early identification of PIR is important given their higher morbimortality compared to adequate immune (AIR). In this study, 33 severely lymphopenic at ART onset, were followed for least 36 months, and classified as or AIR using cluster analysis grounded on count trajectories. Based a variety parameters, we built predictive models...