A5014514500- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Cell Adhesion Molecules Research
- T-cell and B-cell Immunology
- Angiogenesis and VEGF in Cancer
- Cell Image Analysis Techniques
- Cancer Immunotherapy and Biomarkers
- Immune Cell Function and Interaction
- Single-cell and spatial transcriptomics
- Nanoplatforms for cancer theranostics
- Radiomics and Machine Learning in Medical Imaging
- Advanced Biosensing Techniques and Applications
- Cancer, Hypoxia, and Metabolism
- Monoclonal and Polyclonal Antibodies Research
- Industrial Vision Systems and Defect Detection
- 3D Printing in Biomedical Research
- Inflammatory mediators and NSAID effects
- CRISPR and Genetic Engineering
- Retinoids in leukemia and cellular processes
- Virus-based gene therapy research
- Renal and related cancers
- Advanced Fluorescence Microscopy Techniques
- Scheduling and Optimization Algorithms
- Gene expression and cancer classification
- Vagus Nerve Stimulation Research
National Institute of Allergy and Infectious Diseases
2021-2025
National Institutes of Health
2021-2025
Immune Regulation (United Kingdom)
2025
Kyoto University
2016-2023
Baruch S. Blumberg Institute
2016
Although adoptive transfer of cytotoxic T lymphocytes (CTL) offer a promising cancer therapeutic direction, the generation antigen-specific CTL from patients has faced difficulty in efficient expansion ex vivo culture. To resolve this issue, several groups have proposed that induced pluripotent stem cell technology be applied for CTL, which retain expression same T-cell receptor as original CTL. However, these previous studies, regenerated are mostly CD8αα+ innate type and less activity than...
Natural killer (NK) cells lyse invading tumor to limit metastatic growth in the lung, but how some cancers evade this host protective mechanism establish a growing lesion is unknown. Here, we have combined ultra-sensitive bioluminescence imaging with intravital two-photon microscopy involving genetically encoded biosensors examine question. NK eliminated disseminated from lung within 24 hr of arrival, not thereafter. Intravital dynamic revealed that 50% NK-tumor cell encounters lead death...
The iterative bleaching extends multiplexity (IBEX) Knowledge-Base is a central portal for researchers adopting IBEX and related 2D 3D immunofluorescence imaging methods. design of the modeled after efforts in open-source software community includes three facets: development platform (GitHub), static website, service data archiving. facilitates practice open science throughout research life cycle by providing validation recommended non-recommended reagents, e.g., primary secondary...
HLA haplotype-homozygous (HLA-homo) induced pluripotent stem cells (iPSCs) are being prepared to be used for allogeneic transplantation of regenerated tissue into recipients carrying an identical haplotype in one the alleles (HLA-hetero). However, it remains unaddressed whether natural killer (NK) respond these cells. HLA-C allotypes, known serve as major ligands inhibitory receptors NK cells, can classified group 1 (C1) and 2 (C2), based on their binding specificities. We found that T...
Spatial patterns of cells and other biological elements drive physiologic pathologic processes within tissues. While many imaging transcriptomic methods document tissue organization, discerning these is challenging, especially when they involve multiple in complex arrangements. To address this challenge, we present Patterning Analysis Cellular Ensembles (SPACE), an R package for analysis high-plex spatial data. SPACE compatible with any data collection modality that records values (i.e.,...
Multiplexed imaging is a powerful approach in spatial biology, although it complex, expensive and labor-intensive. Here, we present the IBEX Knowledge-Base, central resource for reagents, protocols more, to enhance knowledge sharing, optimization innovation of proteomics techniques.
The iterative bleaching extends multiplexity (IBEX) Knowledge-Base is a central portal for researchers adopting IBEX and related 2D 3D immunofluorescence imaging methods. design of the modeled after efforts in open-source software community includes three facets: development platform (GitHub), static website, service data archiving. facilitates practice open science throughout research life cycle by providing validation recommended non-recommended reagents, e.g., primary secondary...
Current adoptive T cell therapies conducted in an autologous setting are costly, time-consuming, and depend on the quality of patient's cells, thus it would be highly beneficial to develop allogeneic strategy. To this aim, we have developed a method by which cytotoxic lymphocytes (CTLs) regenerated from induced pluripotent stem cells that originally derived (T-iPSCs). In order assess feasibility strategy, investigated frequency usable T-iPSC clones terms their cell-generating capability...
Current adoptive T cell therapies conducted in an autologous setting are costly, time consuming, and depend on the quality of patient's cells. To address these issues, we developed a strategy which cytotoxic lymphocytes (CTLs) regenerated from iPSCs that were originally derived cells succeeded regenerating CTLs specific for WT1 antigen, exhibited therapeutic efficacy xenograft model leukemia. In this study, extended our to solid tumors. The WT1-specific had strong effect orthotopic using...
Prostaglandin E2 (PGE2) promotes tumor progression through evasion of antitumor immunity. In stark contrast to cyclooxygenase-dependent production PGE2, little is known whether PGE2 secretion regulated within tissues. Here, we show that VEGF-dependent release thromboxane A2 (TXA2) triggers Ca2+ transients in cells, culminating and subsequent immune the early stages tumorigenesis. caused cPLA2 activation triggered arachidonic acid cascade. were monitored as surrogate marker secretion....
Macrophages have the potential to undergo cellular transformation into epithelioid cells, and their concentric accumulation in tissues results development of granulomas. Although cells are an essential dominant component granulomas, other cell types also been detected, which may contribute establishment well-organized as observed human granulomatous diseases. We herein demonstrated that neutrophils mediate these functions. By taking advantage guinea pig pulmonary granuloma model, we obtained...
In the current adoptive T cell therapy, cells from a patient are given back to that after ex vivo activation, expansion, or genetic manipulation. However, such strategy depends on quality of patient's cells, sometimes leading treatment failure. It would therefore be ideal use allogeneic as "off-the-shelf" cells. To this aim, we have been developing where potent tumor-antigen-specific cytotoxic lymphocytes (CTLs) regenerated T-cell-derived induced pluripotent stem (T-iPSCs). certain issues...
Abstract Maintaining tissue function while eliminating infected cells is fundamental to host defense. Innate inflammatory damage contributes lethal influenza and COVID-19, yet other than steroids, immunomodulatory drugs have modest effects. Among more 50 regimes tested in mouse infection, only the previously reported early depletion of neutrophils showed efficacy, suggesting that passes an tipping point which limiting innate immune alone cannot rescue physiological function. To re-balance...
Abstract 2D multiplexed antibody-based imaging provides a framework to study cell-cell interactions in thin tissue sections but lacks the ability interrogate spatial relationships larger 3D micro-anatomical structures. Several methods for of optically cleared exist, current approaches do not provide deep phenotyping capability as afforded by high content imaging. Here,we developed method overcome this constraint combining fast hydrophilic clearing technique, clearing-enhanced (Ce3D), and...
Abstract The airway mucosa is a primary site of the immune response to inhaled antigens. However, how homeostasis maintained in this organ during continuous exposure airborne particles and microbial antigens not known. Previous studies have shown that spatial organization components relationship each other non-hematopoietic tissues critical their proper function. To interrogate such relationships lung, 3D information required. current methods for fluorescence imaging do provide marker depth...
Abstract Solid tumors are innervated by distinct branches of the peripheral nervous system, and increased tumor innervation has been associated with poor cancer outcomes. However, it remains unexplored whether different types nerves function together to sense respond a tumor, how neural networks shape immunity. As major interoceptive vagal large variety body signals critical for maintaining physiological homeostasis visceral organs including lung. While sensory neuron (VSN) subtypes have...
IFN-γ secreted from immune cells exerts pleiotropic effects on tumor cells, including induction of checkpoint and antigen presentation, growth inhibition, apoptosis induction. We combined a dual promoter system with an signaling responsive to generate reporter named the interferon sensing probe (ISP), which quantitates response by means fluorescence bioluminescence. The integration site effect transgene is compensated for PGK promoter-driven expression fluorescent protein. Among five...
Abstract 2D multiplexed antibody-based imaging provides a framework to study cell-cell interactions in thin tissue sections but lacks the ability interrogate spatial relationships larger 3D anatomical structures. Several methods for of optically cleared exist, current approaches do not provide marker depth afforded by high content imaging. To overcome this constraint, we combined fast hydrophilic clearing technique, clearing-enhanced (Ce3D), with recently developed Iterative Bleaching...
ABSTRACT Natural killer (NK) cells lyse invading tumor to limit metastatic growth in the lung, but how some cancers evade this host protective mechanism establish a growing lesion is not known. Here we have combined ultra-sensitive bioluminescence whole body imaging with intravital two-photon microscopy involving genetically-encoded biosensors examine question. NK eliminated disseminated from lung within 24 hrs of arrival, thereafter. Intravital dynamic revealed that cell pulmonary capillary...
Abstract Current cancer immunotherapies mainly aim to activate and expand tumor antigen specific cytotoxic T lymphocytes (CTLs) in vitro or vivo, but these methods are not so successuful because of the difficulty preparing sufficient number CTLs. We trying overcome this problem by utilizing induced pluripotent stem cell (iPSC) technology. Our strategy is based on concept that i) when iPSCs produced from cells, rearranged configurations receptor (TCR) genes inherited (which we call T-iPSCs),...