A5084275731- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Viral-associated cancers and disorders
- Monoclonal and Polyclonal Antibodies Research
- Glycosylation and Glycoproteins Research
- CAR-T cell therapy research
- Cytomegalovirus and herpesvirus research
- Lymphoma Diagnosis and Treatment
- Herpesvirus Infections and Treatments
- Aquatic Ecosystems and Phytoplankton Dynamics
- Cell Adhesion Molecules Research
- T-cell and Retrovirus Studies
- Cancer Immunotherapy and Biomarkers
- Psoriasis: Treatment and Pathogenesis
- interferon and immune responses
- Immune Response and Inflammation
- Diabetes and associated disorders
- Autoimmune Bullous Skin Diseases
- Soil and Water Nutrient Dynamics
- HIV Research and Treatment
- Ecology and Vegetation Dynamics Studies
- Allergic Rhinitis and Sensitization
- Stress Responses and Cortisol
- Peptidase Inhibition and Analysis
University of California, San Francisco
2024-2025
University of California, Davis
2015-2024
UC Davis Comprehensive Cancer Center
2021-2024
OASIS Clinic
2022
Augusta University
2006-2018
Tokoha Gakuen University
2018
Fuji Tokoha University
2009-2018
Chiba University
2011-2016
Georgia Regents Medical Center
2013-2015
Augusta University Health
2012-2013
Reexpression of the V(D)J recombinase-activating genes RAG1 and RAG2 in germinal center B cells creates potential for immunoglobulin gene rearrangement generation new antigen receptor specificities. Intermediate products recombination are abundant a subset cells, demonstrating that κ light-chain locus becomes substrate renewed recombinase activity. This recombinationally active cell compartment contains many heavy-chain VDJ rearrangements encode low-affinity or nonfunctional antibody. In...
Membrane-bound oligosaccharides form the interfacial boundary between cell and its environment, mediating processes such as adhesion signaling. These structures can undergo dynamic changes in composition expression based on type, external stimuli, genetic factors. Glycosylation, therefore, is a promising target of therapeutic interventions for presently incurable forms advanced cancer. Here, we show that cholangiocarcinoma metastasis characterized by down-regulation Golgi α-mannosidase I...
B cells are increasingly regarded as integral to the pathogenesis of multiple sclerosis, in part a result success cell-depletion therapy. Multiple cell-dependent mechanisms contributing inflammatory demyelination CNS have been explored using experimental autoimmune encephalomyelitis (EAE), CD4 T animal model for sclerosis. Although cell Ag presentation was suggested regulate inflammation during EAE, direct evidence that can independently support Ag-specific responses by EAE is lacking. Using...
Pyoderma gangrenosum (PG) is a debilitating ulcerative skin disease that one of the most common associated diseases seen in patients with inflammatory bowel and rheumatoid arthritis. Although PG classified as neutrophilic dermatosis, its pathophysiology poorly understood.Use data obtained from patient-reported histories, immunohistochemistry, gene expression analysis to formulate hypothesis on pathophysiology.Ten participated answered questions about new ulcer formation. Skin biopsies healed...
Kaposi sarcoma-associated herpesvirus (KSHV) establishes a latent infection in the cell nucleus, but where KSHV episomal genomes are tethered and mechanisms underlying lytic reactivation unclear. Here, we study nuclear microenvironment of episomes show that latency-lytic replication switch is regulated via viral long non-coding (lnc)RNA-CHD4 (chromodomain helicase DNA binding protein 4) interaction. localize with CHD4 ADNP proteins, components cellular ChAHP complex. The proteins occupy...
The role of apoptosis in affinity maturation was investigated by determining the (4-hydroxy-3-nitrophenyl)acetyl (NP)-specific antibody-forming cells (AFCs) and serum antibody transgenic mice that overexpress a suppressor apoptosis, Bcl-xL, B cell compartment. Although animals briefly expressed higher numbers splenic AFCs after immunization, bcl-xL transgene did not increase number or size germinal centers (GCs), alter levels antibody, change frequency NP-specific, long-lived AFCs....
CD40L plays a major role in immune response and is therapeutic target for inflammation. Integrin α5β1 CD40 simultaneously bind to CD40L. It unclear if work together CD40/CD40L signaling or how binds In this article, we describe that the integrin-binding site of human predicted be located trimeric interface by docking simulation. Mutations markedly reduced binding Several mutants defective integrin were NF-κB activation B cell suppressed induced wild-type CD40L; however, they still bound...
The identification of therapeutic strategies to induce sustained antiretroviral therapy (ART)-free control HIV infection is a major priority. Combination immunotherapy including vaccination, immune stimulation/latency reversal, and passive transfer broadly neutralizing antibodies (bNAbs) has shown promise in non-human primate models, but few studies have translated such approaches into people. Here, we performed single-arm, proof-of-concept combination study these three ten people with on...
Mucosal immunoglobulin (Ig)A dominance has been proposed to be associated with preferential class switch recombination (CSR) the IgA heavy chain constant region, Cα. Here, we report that B cell activation in nasal-associated lymphoid tissue (NALT) upon stimulation hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) coupled chicken γ globulin caused an anti-NP memory response dominated by high affinity antibodies. In response, however, NP-specific IgG+ cells expanded and sustained their number as a...
A discrete population of splenocytes with attributes dendritic cells (DCs) and coexpressing the B-cell marker CD19 is uniquely competent to express T-cell regulatory enzyme indoleamine 2,3-dioxygenase (IDO) in mice treated TLR9 ligands (CpGs). Here we show that IDO-competent B-lineage commitment factor Pax5 surface immunoglobulins. ablation abrogated IDO-dependent suppression by DCs, even though phenotypic matching developed normally expressed IDO response interferon γ. Consequently, DCs T...
Humoral responses to nonproteinaceous Ags (i.e., T cell independent [TI]) are a key component of the early response bacterial and viral infection critical driver systemic autoimmunity. However, mechanisms that regulate TI humoral immunity poorly defined. In this study, we report B cell-intrinsic induction tryptophan-catabolizing enzyme IDO1 is mechanism limiting Ab responses. When Ido1(-/-) mice were immunized with Ags, there was significant increase in titers formation extrafollicular...
Primary effusion lymphoma (PEL) is an aggressive subtype of non-Hodgkin caused by Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Currently, treatment options for patients with PEL are limited. Oncolytic viruses have been engineered as anticancer agents and recently shown increased therapeutic promise. Similarly, lytic activation endogenous from latently infected tumor cells can also be applied a cancer therapy. In theory, such strategy would induce oncolysis viral replication,...
It is widely accepted that central and effector memory CD4+ T cells originate from naïve after they have encountered their cognate antigen in the setting of appropriate co-stimulation. However, if this were true diversity cell receptor (TCR) sequences within compartment should be far greater than compartment, which not supported by TCR sequencing data. Here we demonstrate aged mice with fewer cells, respond to model antigen, hen eggwhite lysozyme (HEL), utilizing same sequence as younger...
Abstract The goal of this pilot study was to determine whether HDL glycoprotein composition affects HDL’s immunomodulatory function. were purified from healthy controls (n = 13), subjects with metabolic syndrome (MetS) and diabetic hemodialysis (HD) patients 24). Concentrations HDL-bound serum amyloid A (SAA), lipopolysaccharide binding protein (LBP), apolipoprotein A-I (ApoA-I), C-III (ApoC-III), α-1-antitrypsin (A1AT), α-2-HS-glycoprotein (A2HSG); the site-specific glycovariations...
Abstract CD40/CD40L engagement is essential to T cell-dependent B cell proliferation and differentiation. However, the precise role of CD40 signaling through cognate T–B interaction in generation germinal center memory cells still incompletely understood. To address this issue, a cell-specific CD40L transgene (CD40LBTg) was introduced into mice with cell-restricted MHC class II deficiency. Using mouse model, we show that constitutive expression on alone could not induce differentiation...
Kaposi’s sarcoma-associated herpesvirus (KSHV) is an oncogenic double-stranded DNA virus and the etiologic agent of sarcoma hyperinflammatory lymphoproliferative disorders. Understanding mechanism by which KSHV increases infected cell population crucial for curing KSHV-associated diseases. Using scRNA-seq, we demonstrate that preferentially infects CD14 + monocytes, sustains viral lytic replication through interleukin-6 (vIL-6), activates STAT1 3, induces inflammatory gene expression...
Immunobullous diseases mediated by IgA are often difficult to manage, but date no mechanism has been proposed. Rituximab is an anti-CD20 monoclonal antibody that demonstrated good efficacy in the treatment of refractory mucous membrane pemphigoid. However, not all cases pemphigoid respond rituximab. Herein we present a case treatment-refractory and propose explain lack response therapy.Before treatment, direct immunofluorescent examination biopsy sample from patient's perilesional skin...
Therapeutic applications for mesenchymal stem/stromal cells (MSCs) are growing; however, the successful implementation of these therapies requires development appropriate MSC delivery systems. Hydrogels ideally suited to cultivate MSCs but tuning hydrogel properties match their specific in vivo remains a challenge. Thus, further characterization how hydrogel-based vehicles broadly influence function and fate will help lead next generation more intelligently designed vehicles. To date, few...
CD40L is a member of the TNF superfamily that participates in immune cell activation. It binds to and signals through several integrins, including αvβ3 α5β1, which bind trimeric interface CD40L. We previously showed integrin ligands can allosteric site (site 2), distinct from classical ligand-binding 1), raising question if activates integrins. In our explorations this question, we determined α4β1, prevalently expressed on same CD4+ T cells as CD40L, another receptor for Soluble (s)CD40L...
Abstract We investigated the role of B cell Ag presentation in homeostasis memory compartment a mouse model where conditional allele for β-chain MHC class II (MHC-II) is deleted vast majority all cells by cd19 promoter-mediated expression Cre recombinase (IA-B mice). Upon T cell-dependent immunization, small number MHC-II+ IA-B mice dramatically expanded and restored normal albeit delayed levels germinal center (GC) with an affinity-enhancing somatic mutation to Ag. also established cells,...
Abstract Although the importance of MHC class II (MHC-II) in acute homeostatic proliferation regulatory T (Treg) cells has been established, we considered here maintenance and state Treg mice that are almost completely devoid MHC-II their periphery but still make own CD4 cells. The latter was accomplished by conditional deletion a loxP-flanked β-chain allele using TIE2Cre transgene, which causes very high degree hemopoietic/endothelial progenitor without among thymic epithelial Such...