A5082209156- Nitrogen and Sulfur Effects on Brassica
- Asthma and respiratory diseases
- Dermatology and Skin Diseases
- Allergic Rhinitis and Sensitization
- Immune cells in cancer
- Immune Cell Function and Interaction
- Cancer, Hypoxia, and Metabolism
- Epigenetics and DNA Methylation
- Cancer Research and Treatments
- IL-33, ST2, and ILC Pathways
- Mast cells and histamine
- Folate and B Vitamins Research
- RNA modifications and cancer
- T-cell and B-cell Immunology
- PI3K/AKT/mTOR signaling in cancer
- Food Allergy and Anaphylaxis Research
- Cancer Immunotherapy and Biomarkers
- Protein Tyrosine Phosphatases
- Ferroptosis and cancer prognosis
- Melanoma and MAPK Pathways
- Lung Cancer Treatments and Mutations
- Garlic and Onion Studies
- Liver physiology and pathology
- Adenosine and Purinergic Signaling
- Glutathione Transferases and Polymorphisms
Dankook University
2024
Johns Hopkins University
2012-2023
Sidney Kimmel Comprehensive Cancer Center
2016-2023
Bloomberg (United States)
2017-2023
Cancer Research Center
2016-2023
Yale University
2017-2023
Korea National University of Transportation
2023
University of British Columbia
2017-2021
Johns Hopkins Medicine
2008-2020
University of Baltimore
2020
The metabolic characteristics of tumors present considerable hurdles to immune cell function and cancer immunotherapy. Using a glutamine antagonist, we metabolically dismantled the immunosuppressive microenvironment tumors. We demonstrate that blockade in tumor-bearing mice suppresses oxidative glycolytic metabolism cells, leading decreased hypoxia, acidosis, nutrient depletion. By contrast, effector T cells responded antagonism by markedly up-regulating adopting long-lived, highly activated...
Atopic dermatitis (AD) is an inflammatory disease characterized by pruritic skin lesions. The pathogenesis of AD may include disrupted epidermal barrier function, immunodysregulation, and IgE-mediated sensitization to food environmental allergens. also part a process called the atopic march, progression from allergic rhinitis asthma. This has been supported multiple cross-sectional longitudinal studies experimental data. Research on mechanisms centered adaptive immune system with emphasis...
Activation of mTOR-dependent pathways regulates the specification and differentiation CD4+ T effector cell subsets. Herein, we show that mTOR complex 1 (mTORC1) mTORC2 have distinct roles in generation CD8+ memory populations. Evaluation mice with a cell-specific deletion gene encoding negative regulator mTORC1, tuberous sclerosis 2 (TSC2), resulted highly glycolytic potent cells; however, due to constitutive mTORC1 activation, these cells retained terminally differentiated phenotype were...
Myeloid cells comprise a major component of the tumor microenvironment (TME) that promotes growth and immune evasion. By employing small-molecule inhibitor glutamine metabolism, not only were we able to inhibit growth, but markedly inhibited generation recruitment myeloid-derived suppressor (MDSCs). Targeting metabolism led decrease in CSF3 hence MDSCs as well immunogenic cell death, leading an increase inflammatory tumor-associated macrophages (TAMs). Alternatively, inhibiting themselves...
Abstract Allergic asthma is characterized by airway inflammation initiated adaptive immune responses to aeroallergens. Recent data suggest that severe may be a different form of rather than an increase in symptoms and innate LPS can modulate allergens. In this study, we evaluated the hypothesis exposure doses induces asthma. Our study showed neutrophilic IFN-γ expression were higher induced sputum from patients mild moderate asthmatics. Animal experiments indicated allergen sensitization...
Abstract Chronic debilitating pruritus is a cardinal feature of atopic dermatitis (AD). Little known about the underlying mechanisms. Antihistamines lack efficacy in treating itch AD, suggesting existence histamine-independent pathways AD. Transient receptor potential ankyrin 1 (TRPA1) essential signaling that promote itch. In this study, we tested hypothesis TRPA1-dependent neural play key role chronic AD using an IL-13–transgenic mouse model these mice, IL-13 causes characterized by...
Skin fibrotic remodeling is a major feature in human atopic dermatitis (AD). Inflammation and tissue fibrosis are common consequences of Th2 responses. Elevated IL-13 thymic stromal lymphopoietin (TSLP) have been found the AD skin lesions. Fibrocytes can be recruited to inflamed tissues promote wound healing fibrosis. Dermal transgenic expression causes an AD-like phenotype with increased TSLP. However, role TSLP unknown. In this study, we investigated fibrocytes generation IL-13-induced...
Abstract The mechanistic/mammalian target of rapamycin (mTOR) has emerged as a critical integrator signals from the immune microenvironment capable regulating T cell activation, differentiation, and function. precise role mTOR in control regulatory (Treg) differentiation function is complex. Pharmacologic inhibition genetic deletion promotes generation Tregs even under conditions that would normally promote effector cells. Alternatively, activity been observed to be increased Tregs, complex...
Abstract Increased expression of Th22 cytokine IL-22 is a characteristic finding in atopic dermatitis (AD). However, the specific role pathogenesis AD vivo has yet to be elucidated. Consistent with observations human AD, was significantly increased skin mice after epicutaneous sensitization house dust mite allergen. Utilizing skin-specific inducible transgenic system, we show present study that caused an AD-like phenotype characterized by chronic pruritic associated Th2-biased local and...
Abstract Alternatively activated macrophages (M2) have an important function in innate immune responses to parasitic helminths, and emerging evidence also indicates these cells are regulators of systemic metabolism. Here we show a critical role for mTORC2 signalling the generation M2 macrophages. Abrogation by selective conditional deletion adaptor molecule Rictor inhibits while leaving classically (M1) intact. Selective prevents differentiation clearance helminth infection mice, abrogates...
Synthetic lethality results when mutant KRAS and EGFR proteins are co-expressed in human lung adenocarcinoma (LUAD) cells, revealing the biological basis for mutual exclusivity of mutations. We have now defined biochemical events responsible toxic effects by combining pharmacological genetic approaches to show that signaling through extracellular signal-regulated kinases (ERK1/2) mediates toxicity. These findings imply tumors with oncogenes RAS pathway must restrain activity ERK1/2 avoid...
Metabolic programming is integrally linked to immune cell function. Nowhere this clearer than in the differentiation of macrophages. Proinflammatory M1 macrophages primarily use glycolysis as a rapid energy source but also generate antimicrobial compounds, whereas alternatively activated M2 rely on oxidative phosphorylation for longevity required proper wound healing. mTOR signaling has been demonstrated be key regulator metabolism and mTORC2 generation macrophages, role mTORC1 signaling,...
T cell activation, proliferation, function, and differentiation are tightly linked to proper metabolic reprogramming regulation. By using [U-13C]glucose tracing, we reveal a critical role for GOT1 in promoting CD8+ effector function. Mechanistically, enhances proliferation by maintaining intracellular redox balance serine-mediated purine nucleotide biosynthesis. Further, promotes the glycolytic programming cytotoxic function of lymphocytes via posttranslational regulation HIF protein,...
Tissue-resident macrophages play critical roles in sentinel and homeostatic functions as well promoting inflammation immunity. It has become clear that the generation of these cells is highly dependent upon tissue-specific cues derived from microenvironment that, turn, regulate unique differentiation programs. Recently, a role for GATA6 emerged programming resident peritoneal macrophages. We identify mTOR integrating tissue regulating metabolic reprogramming. Specifically, inhibition mTORC2...
Current immunotherapies for lung cancer are only effective in a subset of patients. Identifying tumor-derived factors that facilitate immunosuppression offers the opportunity to develop novel strategies supplement and improve current therapeutics. We sought determine whether expression driver oncogenes cells affects cytokine secretion, alters local immune environment, influences tumor progression. demonstrate oncogenic EGFR KRAS mutations, which early events tumourigenesis, can drive...
Although atopic dermatitis (AD) is the initial step of "atopic march", a progression from AD to asthma, underlying mechanism remains unknown. Selective expression IL-13 in skin mice caused an phenotype resembling human AD, and disorder was associated with enhanced production thymic stromal lymphopoietin (TSLP) systemic Th2 immunity. Here we show that transgenic had significantly lung inflammation, mucus hypersecretion, airway hyperresponsiveness (AHR) when sensitized challenged by allergen....
Idiopathic pulmonary fibrosis (IPF) is a fatal disease without any cure. Both human and animal models demonstrate dysregulated wound healing unregulated fibrogenesis in background of low-grade chronic T lymphocyte infiltration. Tissue-resident memory cells (Trm) are emerging as important regulators the immune microenvironment response to pathogens, we hypothesized that they might play role regulating unremitting inflammation promotes lung fibrosis. Herein, lung-directed immunotherapy, form...