A5015508919- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- IL-33, ST2, and ILC Pathways
- CAR-T cell therapy research
- Single-cell and spatial transcriptomics
- Cell Adhesion Molecules Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Atherosclerosis and Cardiovascular Diseases
- Occupational and environmental lung diseases
- Influenza Virus Research Studies
- Bamboo properties and applications
- Reproductive System and Pregnancy
- Histone Deacetylase Inhibitors Research
- Advanced Fluorescence Microscopy Techniques
- Immune cells in cancer
- Multiple Myeloma Research and Treatments
- Noise Effects and Management
- Bioenergy crop production and management
- Adrenal Hormones and Disorders
- Whipple's Disease and Interleukins
- Macrophage Migration Inhibitory Factor
- Air Quality and Health Impacts
- Cellular Mechanics and Interactions
- Cytomegalovirus and herpesvirus research
Columbia University Irving Medical Center
2018-2025
Columbia University
2019-2021
Tribhuvan University
2018
Mayo Clinic
2010-2017
Mayo Clinic in Arizona
2013-2016
WinnMed
2010-2014
Human T cells coordinate adaptive immunity in diverse anatomic compartments through production of cytokines and effector molecules, but it is unclear how tissue site influences cell persistence function. Here, we use single RNA-sequencing (scRNA-seq) to define the heterogeneity human isolated from lungs, lymph nodes, bone marrow blood, their functional responses following stimulation. Through analysis >50,000 resting activated cells, reveal signatures mucosal lymphoid sites, lineage-specific...
Actin depolymerizing factor-homology (ADF-H) family proteins regulate actin filament dynamics at multiple cellular locations. Herein, we have investigated the function of ADF-H member coactosin-like 1 (COTL1) in regulation T cell immune synapse (IS). We initially identified COTL1 a genetic screen to identify novel regulators activation, and subsequently found that it associates with F-actin localizes IS response TCR+CD28 stimulation. Live microscopy showed depletion protein impaired...
Invariant natural killer T cells have a distinct developmental pathway from conventional αβ cells. Here we demonstrate that the transcriptional repressor NKAP is required for invariant cell but not development. In CD4-cre conditional knockout mice, development blocked at double-positive stage. This cell-intrinsic block due to decreased survival or failure rearrange Vα14-Jα18 receptor-α chain, rescued by overexpression of rec-Vα14-Jα18 transgene stage, thus defining role in selection into...
ABSTRACT The first years of life are essential for the development memory T cells, which rapidly populate body’s diverse tissue sites during infancy. However, degree to cell responses in early reflect those adulthood is unclear. Here, we use single RNA-sequencing resting and ex vivo activated cells from lymphoid mucosal tissues infant (aged 2-9 months) adult 40-65 years) human organ donors dissect transcriptional programming over age. Infant demonstrate a unique stem-like profile adaptation...
NKT cells are a distinct subset that have developmental requirements often differ from conventional T cells. Here, we show NKT-specific deletion of Hdac3 results in severe reduction the number iNKT cells, particularly NKT1 In addition, there is decreased cytokine production by Hdac3-deficient NKT2 and NKT17 increased cell death not rescued transgenic expression Bcl-2 or Bcl-xL. less Cyto-ID staining lower LC3A/B expression, indicative reduced autophagy. Interestingly, also nutrient receptors...
Abstract Invariant NKT (iNKT) cells are a unique lineage with characteristics of both adaptive and innate lymphocytes, they recognize glycolipids presented by an MHC class I–like CD1d molecule. During thymic development, iNKT also differentiate into NKT1, NKT2, NKT17 functional subsets that preferentially produce cytokines IFN-γ, IL-4, IL-17, respectively, upon activation. Newly selected undergo burst proliferation, which is defective in mice specific deletion NKAP the cell lineage, leading...
iNKT cells are a unique lineage of T that recognize glycolipid presented by CD1d. In the thymus, they differentiate into iNKT1, iNKT2 and iNKT17 effector subsets, characterized preferential expression Tbet, Gata3 ROR-γt production IFN-γ, IL-4 IL-17, respectively. We demonstrate transcriptional regulator Runx1 is essential for generation expressing cells. PLZF-cre cKO mice lack in spleen liver. Runx1-deficient have altered several genes important differentiation, including decreased IL-7Rα,...
B-cell-biased lymphoid progenitors (BLPs) and Pre-pro B cells lie at a critical juncture between cell specification commitment. However, both of these populations are heterogenous, which hampers investigation into the molecular changes that occur as commit to lineage. Here, we demonstrate there PDCA-1(+)Siglec H(+) plasmacytoid dendritic (pDCs) co-purify with BLPs cells, express little or no CD11c Ly6C. Removal PDCA-1(+) pDCs separates high levels Rag1-GFP reporter from Rag1-GFP(low/neg)...
Infants require coordinated immune responses to prevent succumbing multiple infectious challenges during early life, particularly in the respiratory tract. The mechanisms by which infant T cells are functionally adapted for these not well understood. Here, we demonstrated using an vivo mouse cotransfer model that generated greater numbers of lung-homing effector response influenza infection compared with adult same host, due augmented cell receptor (TCR)–mediated signaling. Mouse showed...
The concentration of carbon dioxide (CO2) has risen continuously in atmosphere due to human induced activities, and been considered the predominant cause global climate change. Paulowina tomentosa Steud. (P. tomentosa), a multipurpose tree is popular around market for its timber potential role CO2 sequestration. In this study, total biomass five years old newly planted P. estimated. results indicated that average plant was found be 4.52±0.53Kg C Year-1 per i.e. 9.04±1.06-ton ha-1 (assuming...
ABSTRACT Human T cells coordinate adaptive immunity by localization in diverse tissue sites, though blood are the most readily studied. Here, we used single-cell RNA-seq to define functional responses of isolated from human lungs, lymph nodes, bone marrow, and TCR-stimulation. We reveal how tissues relate those blood, activation states for CD4 + CD8 across all including an interferon-response state distinct effector cells. further show profiles individual tumor-associated can be projected...
NKAP and HDAC3 are critical for T cell maturation. physically associate, a point mutation in NKAP, NKAP(Y352A), abrogates this interaction. To evaluate the significance of association maturation, transgenic mice were engineered cre-mediated endogenous gene deletion coupled to induction NKAP(Y352A) or wild type (WT) control transgene, NKAP(WT), double positive thymocytes regulatory cells (Tregs). maturation was normal with NKAP(WT) induction. However, severe defects occurred Treg iNKT...
Abstract iNKT cells differentiate into functional subsets defined as NKT1, NKT2 and NKT17, characterized by their expression of transcription factors, T-bet, GATA3 ROR-γt production IFN-γ, IL-4 IL-17, respectively. In our earlier studies, we showed that the transcriptional repressor NKAP is required for positive selection DP thymocytes lineage, using CD4-cre conditional knockout (cKO) mice. To study role in subsequent stages cell development differentiation, generated PLZF-cre cKO these...
Abstract Invariant Natural Killer T (iNKT) cells are an innate lineage of lymphocytes that can produce copious amount cytokines within hours stimulation. In the thymus, positive selection into iNKT cell occurs at double (DP) stage, before maturation through various stages (stage 0-3) to complete development. NKAP, a transcriptional repressor, is required for conventional lymphocyte development and maturation. NKAP interacts with Hdac3 its repressor function. Previously, using CD4-cre cKO...
Abstract Invariant Natural Killer T cells (iNKT) are innate lineage of lymphocytes with distinct developmental pathway than conventional αβ cells. The transcriptional repressor NKAP is required for early cell development and maturation Using CD4-cre cKO mice, we show that positive selection thymocytes into the iNKT lineage. Deletion using leads to an block in at DP stage. This intrinsic defect was not due decreased thymocyte survival or inability deficient rearrange their Vα14-Jα18 TCR....
Abstract Natural killer (NK) cells are innate immune with the ability to kill tumor without prior exposure. NK express multiple activating and inhibitory receptors in addition low-affinity immunoglobulin G binding receptor CD16. Accumulating evidence implicates a role of not only direct killing cells, but also cancer immunosurveillance preventing metastasis tissues sites. However, at present distribution, diversity tissue driven differences cell function well characterized which may have an...
Abstract Natural killer (NK) cells are innate immune with the inherent ability to kill tumor and virus infected without any prior priming. Recent studies have demonstrated of NK develop adaptive memory tissue residence. However, our understanding human in tissues their site-specific properties is limited. Here we use unique resource established collaboration LiveOnNY elucidate diversity cell phenotypic subsets, functional profile transcriptional signatures non-mucosal mucosal sites. We...
Abstract Infants are highly susceptible to respiratory infections and frequently experience recurrent episodes. Our previous study demonstrated that tissue resident memory T cells (TRM), which critical in mediating long-term protection against pathogens, reduced infant mice compared adult after influenza infection. However, the underlying mechanisms for TRM generation infants is still unknown. preliminary data show have enhanced TCR sensitivity leading increased activation thus biased...