A5103027049- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Toxoplasma gondii Research Studies
- Cytomegalovirus and herpesvirus research
- CAR-T cell therapy research
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Immunodeficiency and Autoimmune Disorders
- Cytokine Signaling Pathways and Interactions
- interferon and immune responses
- Transgenic Plants and Applications
- Herpesvirus Infections and Treatments
- Cell Adhesion Molecules Research
- Toxin Mechanisms and Immunotoxins
- Microbial Metabolism and Applications
- Eosinophilic Disorders and Syndromes
- Viral Infectious Diseases and Gene Expression in Insects
- Inflammatory Myopathies and Dermatomyositis
- Adrenal Hormones and Disorders
- Ginseng Biological Effects and Applications
- Dermatology and Skin Diseases
- Fungal Biology and Applications
- Occupational exposure and asthma
- Pituitary Gland Disorders and Treatments
- Biosimilars and Bioanalytical Methods
National Institutes of Health Clinical Center
2019-2023
United States Food and Drug Administration
2022
Center for Biologics Evaluation and Research
2022
National Institutes of Health
2010-2019
National Cancer Institute
2017-2019
George Washington University
2015-2019
Center for Cancer Research
2017-2019
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2010-2012
Seoul National University Hospital
2007
Seoul National University
2005
Abstract Clinical challenges exist in reducing prostate cancer (PCa) disparities. The RNA splicing landscape of PCa across racial populations has not been fully explored as a potential molecular mechanism contributing to race-related tumour aggressiveness. Here, we identify novel genome-wide, race-specific events critical drivers aggressiveness and therapeutic resistance African American (AA) men. AA-enriched splice variants PIK3CD , FGFR3 TSC2 RASGRP2 contribute greater oncogenic compared...
CD8, but not CD4, T cells are considered critical for control of chronic toxoplasmosis. Although CD8 exhaustion has been previously reported in Toxoplasma encephalitis (TE)–susceptible model, our current work demonstrates that CD4 only become exhausted during toxoplasmosis this dysfunction is more pronounced than cells. Exhausted population expressed elevated levels multiple inhibitory receptors concomitant with the reduced functionality and up-regulation Blimp-1, a transcription factor. Our...
Negative selection and regulatory T (T reg) cell development are two thymus-dependent processes necessary for the enforcement of self-tolerance, both require high-affinity interactions between receptor (TCR) self-ligands. However, it remains unclear if they similarly impacted by alterations in TCR signaling potential. We generated a knock-in allele (6F) ζ chain gene encoding mutant protein lacking capability whose expression is controlled endogenous sequences. Although negative was defective...
CD8 T cells are important for maintaining the chronicity of Toxoplasma gondii infection. In a T. encephalitis susceptible model, we recently demonstrated that CD4 play an essential helper role in maintenance effector response and cell dysfunctionality was linked to exhaustion. However, constituted different subsets with various functions population(s) providing help has not yet been determined. present study, Tfh (T follicular helper), which known be B maturation one main sources IL-21, were...
Abstract We describe the first cases of germline biallelic null mutations in ARPC5, part Arp2/3 actin nucleator complex, two unrelated patients presenting with recurrent and severe infections, early-onset autoimmunity, inflammation, dysmorphisms. This defect compromises multiple cell lineages functions, when protein expression is reestablished in-vitro, complex conformation functions are rescued. As pathophysiological evaluation, we also show that interleukin (IL)−6 signaling distinctively...
The prosurvival factor Bcl-x L prevents excessive γc cytokine signaling in developing T cells.
T cell receptor (TCR) signaling plays a critical role in development, survival and differentiation. In the thymus, quantitative and/or qualitative differences TCR determine fate of developing thymocytes lead to positive negative selection. Recently, it has been suggested that self-reactive cells, escape from selection, should be suppressed periphery by regulatory cells (Tregs) expressing Foxp3 transcription factor. is master factor for not only development but also suppressive activity Treg....
Naïve and memory T cells co-exist in the peripheral cell pool, but cellular mechanisms that maintain balance homeostasis of these two populations remain mostly unclear. To address this question, here, we assessed homeostatic proliferation repopulation kinetics adoptively transferred naïve lymphopenic host mice. We identified distinct tissue-distribution between donor cells, which resulted occupancy pool by naïve-origin short term (4 weeks). explain finding, utilization cytokines IL-7 IL-15...
Unlike IL-7, which is known to be critical for T cell thymic development, the role of IL-21 in this process still controversial. has been shown accelerate recovery mice treated with glucocorticoids and revives peripheral pool aged animals. However, a defect signaling exhibit normal cellularity, challenging importance cytokine developmental process. Using mixed bone marrow chimeric mice, our studies describe multilayered thymopoiesis. In system, IL-21R-deficient cells are unable compete...
Abstract Role of CD8 T cells in immunoprotection against Toxoplasma gondii infection is well established. However, an encephalitis model, immunity functionally impaired (immune exhaustion), leading to reactivation latent infection. Studies from our laboratory have reported that functional defect during chronic primarily exhibited by memory subset cells. Thus restoration dysfunctional response may be critical for maintaining the chronicity and preventing As a first step we evaluated compared...
Abstract The prevailing view of thymocyte selection is that the fate developing cells dictated exclusively by affinity/avidity expressed TCR for self-MHC/self-ligand. We hypothesize there significant plasticity in signaling processes control T cell development and ability to ‘fine-tune’ response, through regulated expression molecules positively or negatively impact response operates maximize repertoire. One example a ‘fine-tuning’ molecule was previously characterized surface protein CD5....
Abstract Thymocyte selection is controlled by signaling motifs (ITAMs) contained within the invariant T cell receptor (TCR) subunits. The current model of thymocyte posits that differences in affinity TCR for self-peptides results response, with low interactions promoting positive and high triggering negative selection. We others previously demonstrated attenuation potential (by mutation zeta chain ITAMs) leads to generation cells express auto-reactive TCRs. However, these did not cause...
Abstract The prevailing view of thymocyte selection is that the fate developing cells dictated exclusively by affinity/avidity expressed TCR for self-MHC/self-ligand. We hypothesize there significant plasticity in signaling processes control T cell development and ability to ‘fine-tune’ response, through regulated expression molecules positively or negatively impact response operates maximize repertoire. One example a ‘fine-tuning’ molecule was previously characterized surface protein CD5....
Abstract Hypersensitivity pneumonitis (HP) is an interstitial lung disease that develops following repeated exposure to inhaled particulate antigens. HP characterized with lymphocytic alveolitis, granuloma formation and fibrosis, categorized as a Th1 disease. However, it remains unclear whether apoptosis in the contributes development of HP. To investigate functional role Fas-mediated HP, Fas(lpr) or FasL(gld)-deficient B6 mice were challenged Saccharopolyspora rectivirgula (SR)...
<h3>Background</h3> The recent advances in adoptive immunotherapy of cancer have led to the FDA approval chimeric antigen receptor modified T (CAR-T) cells targeting CD19 on advanced hematological malignancies, which has resulted dramatic responses large numbers patients. Because several challenges and complexities manufacturing for characterizing CAR-T cell products, it is important optimize their critical quality attributes (CQAs). Herein, we performed a comparative assessment...