A5041542519- Influenza Virus Research Studies
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Respiratory viral infections research
- Diabetes and associated disorders
- Herpesvirus Infections and Treatments
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Protein purification and stability
- Cytomegalovirus and herpesvirus research
- Glycosylation and Glycoproteins Research
- Viral-associated cancers and disorders
- Liver Disease Diagnosis and Treatment
- CAR-T cell therapy research
- Systemic Lupus Erythematosus Research
- Cannabis and Cannabinoid Research
- Diet, Metabolism, and Disease
- Pancreatic and Hepatic Oncology Research
- Cancer-related gene regulation
- Virology and Viral Diseases
- Pharmacy and Medical Practices
- Hemophilia Treatment and Research
- Peripheral Neuropathies and Disorders
Duke University
2014-2023
Nagoya University
2020-2021
Gifu University
2016
Duke Medical Center
2008-2015
Duke University Hospital
2008-2015
Niigata University
2006
Niigata University Medical and Dental Hospital
2004
Medical University of South Carolina
1976
Toranomon Hospital
1974
Kyoto College of Economics
1972
The extracellular domain of the (pro)renin receptor [(P)RR] is cleaved to generate soluble form (P)RR [s(P)RR]. Multiple clinical studies have revealed association between serum/plasma s(P)RR levels and certain diseases, thereby suggesting a potential role for as disease biomarker. Here, we investigated whether site-1 protease (S1P) responsible cleaving s(P)RR. Reduction endogenous S1P with siRNA attenuated generation in Chinese hamster ovary (CHO) cells exogenously expressing human...
Nonalcoholic steatohepatitis (NASH) is a hepatic phenotype of the metabolic syndrome, and increases risk cirrhosis hepatocellular carcinoma (HCC). Although increasing evidence points to therapeutic implications certain types anti-diabetic agents in NASH, it remains be elucidated whether their effects on NASH are independent diabetes. Genetically obese melanocortin 4 receptor-deficient (MC4R-KO) mice fed Western diet murine model that sequentially develops steatosis, HCC presence obesity...
Abstract IL-7 plays a critical role in B cell fate decision by regulating early factor (EBF) expression. However, it was not clear when stimulation is necessary hemato-/lymphopoiesis adult mice. Here we show that pre-proB cells derived from IL-7−/− mice have lost potential, despite up-regulation of EBF expression following stimulation. Pre-proB wild-type can give rise to proB the absence IL-7. In this case, during transition stages occurs normally. contrast, after ∼20 times lower than cells....
Abstract Special AT-rich sequence binding protein 1 (SATB1) is a genome organizer that expressed by T cells. cell development severely impaired in SATB1 null mice; however, because mice die 3 wk of age, the roles have not been well clarified. In this study, we generated and analyzed conditional knockout (cKO) mice, which gene was deleted from all hematopoietic numbers were reduced these mainly deficiency positive selection at CD4+CD8+ double-positive stage during thymus. We also found cKO...
Rag1 and Rag2 gene expression in CD4+CD8+ double-positive (DP) thymocytes depends on the activity of a distant anti-silencer element (ASE) that counteracts an intergenic silencer. However, mechanistic basis for ASE is unknown. Here, we show physically interacts with promoters DP thymocytes, bringing two together to form active chromatin hub. Moreover, functions as classical enhancer can potently activate these absence silencer or other locus elements. In lacking organizer SATB1, identified...
Abstract The ability to culture and expand B cells in vitro has become a useful tool for studying human immunity. A limitation of current methods cell is the capacity support mature proliferation. We developed method efficient activation proliferation naive memory cells. This supports extensive proliferation, with ∼103-fold increases following 8 d 106-fold when cultures are split cultured more days. In culture, significant fraction undergo isotype switching differentiate into plasmacytes....
Immunological tolerance removes or inactivates self-reactive B cells, including those that also recognize cross-reactive foreign antigens. Whereas a few microbial pathogens exploit these "holes" in the cell repertoire by mimicking host antigens to evade immune surveillance, extent which reduces is unknown. Here, we use single-cell cultures determine repertoires of human antigen receptors (BCRs) before (transitional cells) and after (mature second checkpoint both healthy donors patients with...
The rapid appearance of mutations in circulating human influenza viruses and selection for escape from herd immunity require prediction likely variants an annual updating vaccines. identification antibodies that recognize conserved surfaces on the virus hemagglutinin (HA) has prompted efforts to design immunogens might selectively elicit such antibodies.
Abstract Germinal center (GC) B cells at viral replication sites acquire specificity to poorly immunogenic but conserved influenza hemagglutinin (HA) epitopes. Here, high-throughput epitope mapping of local GC is used identify HA selecting cross-reactive antibodies that mediate heterosubtypic protection. A distinct feature this an occlusion in the naive trimeric structure exposed post-fusion occur under low pH conditions during replication. Importantly, systemic immunization by antigen...
Diabetes and obesity contribute to the pathogenesis of nonalcoholic steatohepatitis (NASH) hepatocellular carcinoma (HCC). However, how diabetes accelerate liver tumorigenesis remains be fully understood. Moreover, verify therapeutic potential anti-diabetic drugs, there exists a strong need for appropriate animal models that recapitulate human pathophysiology NASH HCC. We established novel murine model NASH-associated tumors using genetically obese melanocortin 4 receptor-deficient mice fed...
In CD4(-)CD8(-) double-negative thymocytes, the murine Tcrb locus is composed of alternating blocks active and inactive chromatin containing gene segments trypsinogen genes, respectively. Although structure appreciated to be critical for regulated recombination expression segments, molecular mechanisms that maintain integrity these differentially domains are not understood. We localized a boundary between by mapping modifications across interval extending from Prss2 (the most 3' gene) D(β)1....
Accumulating evidence demonstrates that not only sustained elevation of blood glucose levels but also the fluctuation represents key determinants for diabetic complications and mortality. Current closed-loop insulin therapy option is limited to use electronics-based systems, although it poses some technical issues with high cost. Here we demonstrate an electronics-free, synthetic boronate gel-based insulin-diffusion-control device technology can cope fluctuations potentially address...
Phylogenetically and antigenically distinct influenza A B viruses (IAV IBV) circulate in human populations, causing widespread morbidity. Antibodies (Abs) that bind epitopes conserved both IAV IBV hemagglutinins (HAs) could protect against disease by diverse virus subtypes. Only one reported HA Ab, isolated from a combinatorial display library, protects IBV. Thus, there has been so far no information on the likelihood of finding naturally occurring Abs HAs subtypes lineages. We have now...
Antibody titers that inhibit the influenza virus hemagglutinin (HA) from engaging its receptor are accepted correlate of protection infection. Many potent antibodies with broad, intra-subtype specificity bind HA at binding site (RBS). One barrier to broad H1-H3 cross-subtype neutralization is an insertion (133a) between positions 133 and 134 on rim H1 RBS. We describe here a class overcomes this barrier. These genetically unrestricted abundant in human B cell memory compartment. Analysis...
Studies of a monoclonal IgA(λ) protein with both cryo‐ and pyro‐precipitability show that it belongs to the IgA2 subclass is positive for A 2 m(2) allotypic marker. Like other cryoglobulins, this also has an unblocked light chain, its heavy chain V H I subgroup. The first 22 N‐terminal amino acids λ showed less than 65% homology those human chains but 86% identity amyloid fibril reported by others. α appears have more glutamic acid or glutamine, both, isoleucine residues chains.
The first encounter with influenza virus biases later immune responses. This "immune imprinting," formerly from infection within a few years of birth, is in the United States now largely immunization quadrivalent, split vaccine (IIV4 [quadrivalent inactivated vaccine]). In pilot study IIV4 imprinting, we used single-cell cultures, next-generation sequencing, and plasma antibody proteomics to characterize primary responses two infants during their 2 seasonal vaccination. One infant, who...