A5021071795- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Hepatitis C virus research
- CAR-T cell therapy research
- Hepatitis B Virus Studies
- Caveolin-1 and cellular processes
- Liver Disease Diagnosis and Treatment
- Cancer Mechanisms and Therapy
- Mechanisms of cancer metastasis
- Cancer Immunotherapy and Biomarkers
- Cell Adhesion Molecules Research
- Glycosylation and Glycoproteins Research
- Reproductive System and Pregnancy
- NF-κB Signaling Pathways
- Peptidase Inhibition and Analysis
- Lymphoma Diagnosis and Treatment
- Protein Tyrosine Phosphatases
- Histone Deacetylase Inhibitors Research
- Hepatitis Viruses Studies and Epidemiology
- Veterinary Oncology Research
- Sphingolipid Metabolism and Signaling
- Complement system in diseases
- Immune Response and Inflammation
- Cancer Cells and Metastasis
Hepatitis B Foundation
2023
Research Network (United States)
2023
University of Pennsylvania
2014-2019
Philadelphia VA Medical Center
2015-2019
Philadelphia University
2014
Henry Ford Health System
2011-2013
University of Maryland, Baltimore
2010-2013
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center
2010-2011
Sidney Kimmel Comprehensive Cancer Center
2009
Vanderbilt University
2003-2004
Abstract Programmed death-ligand 1 is a glycoprotein expressed on antigen presenting cells, hepatocytes, and tumors which upon interaction with programmed death-1, results in inhibition of antigen-specific T cell responses. Here, we report mechanism inhibiting through small molecule-induced dimerization internalization. This represents checkpoint inhibition, differentiates from anti-programmed antibodies function molecular disruption the death interaction. Testing ligand molecule humanized...
Va14Ja18 natural T (NKT) cells play an immunoregulatory role, which is controlled by a self glycolipid(s) presented CD1d. Although the synthetic antigen α-D-galactosylceramide (α-D-GalCer) stimulates all NKT cells, α-anomeric D-glycosylceramides are currently unknown in mammals. We have used β-D-GalCer-deficient mice and β-D-glucosylceramide (β-D-GlcCer)-deficient to define chemical nature of cell antigen. exhibit normal development function, from these animals potently stimulate hybridomas....
Abstract Chronic hepatitis B (CHB) infection functional cure is defined as sustained loss of HBsAg and several therapeutic strategies are in clinical development designed to pharmacologically reduce serum HBsAg, break immune tolerance, increase rates. However, little known about pre-treatment levels an indicator HBV potential. Here, we compared the phenotypes HBV-specific response lymphocytes CHB patients stratified by <500 (HBs lo ) or >50,000 IU/ml hi using immunological assays (flow...
Abstract Ontogenetic, homeostatic, and functional deficiencies within immunoregulatory natural T (iNKT) lymphocytes underlie various inflammatory immune disorders including autoimmunity. Signaling events that control cell fate specification molecular differentiation of iNKT cells are only partly understood. Here we demonstrate these processes require classical NF-κB signaling. Inhibition signaling blocks ontogeny at an immature stage reveals apparent, novel precursor in which negative...
Abstract Cancers display distinct patterns of organ-specific metastasis. Comparative analysis a broad array cell membrane molecules on liver-metastasizing subline B16 melanoma versus the parental B16-F0 revealed unique up-regulation integrin α2. The direct role α2 in hepatic metastasis was shown by comparison high low-expressing populations, antibody blockade, and ectopic expression. Integrin α2–mediated binding to collagen type IV (highly exposed liver sinusoids) IV–dependent activation...
ErbB3 is markedly overexpressed in breast cancer cells and associated with resistance metastasis. Additionally, expression levels are positively correlated low densities of tumor-infiltrating lymphocytes, a marker poor prognosis. Consequently, promising therapeutic target for immunotherapy. Here, we report the generation ErbB3-targeted chimeric antigen receptor (CAR)-modified natural killer (NK) by transducing cord blood-derived primary NK using vsv-g envelope-pseudotyped lentiviral vectors....
Abstract Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that accompanied by the emergence of autoreactive T cells and reduction in regulatory cells. Humans mice with SLE have reduced numbers CD1d-restricted NK cells, suggesting role for these regulation SLE. In this study, we show CD1d deficiency exacerbates nephritis induced hydrocarbon oil pristane. This exacerbation associated with: 1) TNF-α IL-4 production especially during induction phase; 2) expansion marginal zone...
Abstract The rapid and robust immunoregulatory cytokine response of Va14Ja18 natural T (iNKT) cells to glycolipid Ags determines their diverse functions. Unlike conventional cells, iNKT lymphocyte ontogeny absolutely requires NF-κB signaling. However, the precise role in cell function identity upstream signals that activate this subset remain unknown. Using mice which has been rescued despite inhibition signaling, we demonstrate a lymphocyte-intrinsic manner. Furthermore, functional...
The CD1 family consists of lipid antigen-presenting molecules, which include group I CD1a, CD1b, and CD1c II CD1d proteins. Topologically, they resemble the classical peptide MHC molecules except that large, exclusively nonpolar hydrophobic, antigen-binding groove has evolved to present cellular pathogen-derived antigens specific T lymphocytes. As an approach understanding biochemical basis antigen presentation by we have characterized natural ligands associated with mouse CD1d1 as well...
Disparities in treatment initiation may affect outcomes, but data on racially diverse populations with chronic hepatitis B virus (HBV) infection are limited.To examine whether HBV and outcomes differ among racial groups.From January 14, 2011, to 28, 2018, surface antigen-positive adults (age ≥18 years) not receiving anti-HBV therapy were enrolled followed up at weeks 12, 24, every 24 thereafter a multicenter longitudinal cohort study (Hepatitis Research Network [HBRN] adult study) conducted...
Hepatitis B virus (HBV) persists with global and virus-specific T-cell dysfunction, without based correlates of outcomes. To determine if γδT-cells are altered in HBV infection relative to clinical status, we examined the frequency, phenotype function peripheral blood Vδ1+ Vδ2+γδT-cells by multi-parameter cytometry a clinically diverse North American cohort chronic hepatitis (CHB), acute (AHB) uninfected control subjects. We show that circulating were comprised predominantly CD3hiCD4-...
Programmed death ligand-1 (PD-L1) is an important negative regulator of T cell immune responses via interactions with PD-1 and CD80. However, PD-L1 can also act as a positive costimulator, but the relevant counterreceptor not known. We analyzed role in CD8-T to infection Listeria monocytogenes (LM) or vesicular stomatitis virus (VSV). blockade impaired antigen-specific CD8 effector expansion response LM, VSV infection, particularly limiting short-lived differentiation. Simultaneous CD4-T...
Abstract IFN-producing killer dendritic cells (IKDC) represent a recently discovered cell type in the immune system that possesses number of functions contributing to innate and adaptive immunity, including production 1 2 IFNs, interleukin (IL)-12, natural killing, ultimately antigen presentation naïve T cells. Here, we compared vitro vivo responses mouse IKDC, conventional (DC), (NK) murine cytomegalovirus infection found distinct among these subsets. Upon recognition infected fibroblasts,...
Allosteric inhibitors of mitogen-activated protein kinase 1 (MEK1) reveal distinct interactions with MEK1 activation loop residues. The structural analyses will determine whether, and how, suppress the phosphorylation may guide future therapeutic development. In this study, we explored suppression mechanism process in presence MEK allosteric inhibitors, such as selumetinib, trametinib, cobimetinib, CH5126766, by employing molecular dynamics simulations accompanied principal component...
An amendment to this paper has been published and can be accessed via a link at the top of paper.
The antiviral effects of hepatitis C virus (HCV)-specific CD8 T cells have been shown in an HCV replicon system but not authentic infectious cell culture (HCVcc) system. Here, we developed tools to examine the antigenicity HCV-infected HLA-A2-positive Huh7.5 hepatoma (Huh7.5A2 cells) activating HCV-specific and downstream effects. Infectious epitope mutants encoding well-defined genotype 1a-derived HLA-A2-restricted NS3-1073 or NS5-2594 were generated from a 2a-derived clone (Jc1Gluc2A) by...
Symptoms of chronic hepatitis B (CHB) are not well characterized.To evaluate CHB symptoms and associations with disease activity clinical outcomes.Longitudinal data from 1,576 participants in the Hepatitis Research Network Cohort Study who completed symptom assessments were analyzed. A composite score was calculated using a Symptom Checklist (0=none to 40=extreme). Multivariable mixed models assessed variables associated change over time. Latent class trajectories evaluated. The cumulative...