A5002370058- Ion Channels and Receptors
- Signaling Pathways in Disease
- Ion channel regulation and function
- Neurobiology and Insect Physiology Research
- Immune Cell Function and Interaction
- RNA Interference and Gene Delivery
- Peptidase Inhibition and Analysis
- CAR-T cell therapy research
- Plant Stress Responses and Tolerance
- Cancer-related gene regulation
- Toxin Mechanisms and Immunotoxins
- Calpain Protease Function and Regulation
- Epigenetics and DNA Methylation
- Biochemical and Molecular Research
- CRISPR and Genetic Engineering
- Phytochemicals and Antioxidant Activities
- Immunotherapy and Immune Responses
- RNA modifications and cancer
- T-cell and B-cell Immunology
- Respiratory and Cough-Related Research
- Neuropeptides and Animal Physiology
- Pain Mechanisms and Treatments
- Molecular Communication and Nanonetworks
- RNA Research and Splicing
- Biochemical and Structural Characterization
La Jolla Institute for Immunology
2014-2024
University of California, San Diego
2018-2024
Moores Cancer Center
2019-2024
Biologie du Fruit et Pathologie
2024
Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
2024
UC San Diego Health System
2024
Harvard University
2003-2018
University of Colorado Denver
2018
Harvard University Press
2010-2013
Boston Children's Hospital
2009-2012
T cells expressing chimeric antigen receptors (CAR cells) have shown impressive therapeutic efficacy against leukemias and lymphomas. However, they not been as effective solid tumors because become hyporesponsive ("exhausted" or "dysfunctional") within the tumor microenvironment, with decreased cytokine production increased expression of several inhibitory surface receptors. Here we define a transcriptional network that mediates CD8+ cell exhaustion. We show high-mobility group (HMG)-box...
Nuclear factor of activated T cells (NFAT) is a transcription that regulates expression the cytokine interleukin-2 (IL-2) in cells. The DNA-binding specificity NFAT conferred by NFATp, phosphoprotein target for immunosuppressive compounds cyclosporin A and FK506. Here, purification NFATp from murine isolation complementary DNA clone encoding are reported. truncated form expressed as recombinant protein bacteria, binds specifically to site IL-2 promoter forms transcriptionally active complex...
Stimulation of immune cells triggers Ca2+ entry through store-operated release-activated channels, promoting nuclear translocation the transcription factor NFAT. Through genome-wide RNA interference screens in Drosophila, we and others identified olf186-F (Drosophila Orai, dOrai) dStim as critical components showed that dOrai its human homologue Orai1 are pore subunits channel. Here report is predominantly responsible for influx embryonic kidney 293 T fibroblasts, although paralogue Orai3...
ORAI1 is a pore subunit of the store-operated Ca(2+) release-activated (CRAC) channel. To examine physiological consequences deficiency, we generated mice with targeted disruption Orai1 gene. The results immunohistochemical analysis showed that expressed in lymphocytes, skin, and muscle wild-type not Orai1(-/-) mice. inbred C57BL/6 background perinatal lethality, which was overcome by crossing them to outbred ICR were small size, eyelid irritation sporadic hair loss resembling cyclical...
Significance Cancer cells can be recognized and attacked by CD8 + cytolytic T cells, but tumor-infiltrating often become functionally incompetent (“exhausted”) fail to destroy tumor cells. We show that T-cell exhaustion requires antigen recognition By examining the transcriptional chromatin accessibility profiles of antigen-reactive -unreactive we confirm our previous conclusion transcription factor NFAT promotes identify Nr4a factors as new targets for future investigation. anti–PD-L1...
Nuclear factor of activated T cells (NFAT) proteins are Ca 2+ -regulated transcription factors that control gene expression in many cell types. NFAT heavily phosphorylated and reside the cytoplasm resting cells; when stimulated by a rise intracellular , dephosphorylated / calmodulin -dependent phosphatase calcineurin translocate to nucleus activate target expression. Here we show NFAT1 is present large cytoplasmic RNA-protein scaffold complex contains long intergenic noncoding RNA (lincRNA),...
The application of current channelrhodopsin-based optogenetic tools is limited by the lack strict ion selectivity and inability to extend spectra sensitivity into near-infrared (NIR) tissue transmissible range. Here we present an NIR-stimulable platform (termed 'Opto-CRAC') that selectively remotely controls Ca2+ oscillations Ca2+-responsive gene expression regulate function non-excitable cells, including T lymphocytes, macrophages dendritic cells. When coupled upconversion nanoparticles,...