A5022283280- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Angiogenesis and VEGF in Cancer
- Single-cell and spatial transcriptomics
- Immunotherapy and Immune Responses
- Immune cells in cancer
- Immune Response and Inflammation
- Lymphatic System and Diseases
- Chemokine receptors and signaling
- Cell Adhesion Molecules Research
- Platelet Disorders and Treatments
- NF-κB Signaling Pathways
- Blood Coagulation and Thrombosis Mechanisms
- Cancer Cells and Metastasis
- Cancer Immunotherapy and Biomarkers
- RNA Research and Splicing
- Hemophilia Treatment and Research
- Zebrafish Biomedical Research Applications
- Protease and Inhibitor Mechanisms
- Congenital heart defects research
- Atherosclerosis and Cardiovascular Diseases
- Hematopoietic Stem Cell Transplantation
- Ubiquitin and proteasome pathways
- Sphingolipid Metabolism and Signaling
- Peptidase Inhibition and Analysis
Palo Alto Veterans Institute for Research
2014-2025
Stanford University
2008-2025
VA Palo Alto Health Care System
1999-2024
Palo Alto University
2019-2021
Soochow University
2016
Hoshi University
2015
Bayer (United States)
2007-2015
Palo Alto Institute
2014
Bayer (France)
2004
Virginia BioTechnology Research Park
2002-2003
The immune system has evolved specialized cellular and molecular mechanisms for targeting regulating responses at epithelial surfaces. Here we show that small intestinal intraepithelial lymphocytes lamina propria migrate to thymus-expressed chemokine (TECK). This attraction is mediated by CC receptor (CCR)9, a chemoattractant expressed high levels essentially all CD4+ CD8+ T in the intestine. Only subset of colon are CCR9+, from other tissues including tonsils, lung, inflamed liver, normal...
Mast cells contribute importantly to both protective and pathological IgE-dependent immune responses. We show that the mast cell–expressed orphan serpentine receptor mCCRL2 is not required for expression of IgE-mediated cell–dependent passive cutaneous anaphylaxis but can enhance tissue swelling leukocyte infiltrates associated with such reactions in mice. further identify chemerin as a natural nonsignaling protein ligand human mouse CCRL2. In contrast other “silent” or professional...
Abstract Mucosae-associated epithelial chemokine (MEC) is a novel whose mRNA most abundant in salivary gland, with strong expression other mucosal sites, including colon, trachea, and mammary gland. MEC constitutively expressed by cells; detected cultured bronchial gland cell lines epithelia isolated from colon using laser capture microdissection, but not the endothelial, hemolymphoid, or fibroblastic tested. Although poorly skin, its closest homologue keratinocyte-expressed cutaneous T...
We show that developmental transitions during thymocyte maturation are associated with dramatic changes in chemotactic responses to chemokines. Macrophage-derived chemokine, a chemokine expressed the thymic medulla, attracts thymocytes only brief window of development, between late cortical and early medullary stages. All phenotypes (CD4 or CD8 single positive) but not immature respond stroma-expressed (and secondary lymphoid tissue-associated) chemokines lymphoid-tissue macrophage...
During acute inflammation, P-selectin is transiently mobilized from Weibel-Palade bodies to the surface of histamine-activated endothelial cells, where it mediates rolling adhesion neutrophils under hydrodynamic flow. chronic or allergic sustained expression on cell has been observed. We found that cytokines interleukin 4 (IL-4) oncostatin M (OSM) induced a five- ninefold increase in messenger RNA (mRNA) human umbilical vein cells (HUVEC) persisted as long 72 h. IL-4 elevated mRNA by...
Immunoglobulin A (IgA) provides protection against pathogens at mucosal surfaces. Chemotactic responses have been hypothesized to target IgA plasma cells involved in immune responses. We show here that thymus-expressed chemokine (TECK, CCL25) is a potent and selective chemoattractant for antibody-secreting (ASC), efficiently recruiting IgA-producing from spleen, Peyer's patches, mesenteric lymph node. Cells secreting antibody response rotavirus, an intestinal pathogen, also respond well. In...
C-type natriuretic peptide (CNP) is a member of the family that involved in variety homeostatic processes. Here we characterize processing essential for conversion precursor, human pro-CNP, to biologically active hormone. In embryonic kidney 293 and chondrosarcoma SW 1353 cells, recombinant pro-CNP was converted into mature intracellularly as detected by Western analysis. Expression corin, proatrial convertase, did not enhance these cells. The inhibited presence an inhibitor endoprotease...
Single-cell transcriptomics promises to revolutionize our understanding of the vasculature. Emerging computational methods applied high dimensional single cell data allow integration results between samples and species, illuminate diversity underlying developmental architectural organization populations. Here, we illustrate these in analysis mouse lymph node (LN) lymphatic endothelial cells (LEC) at resolution. Clustering identifies five well-delineated subsets, including two medullary sinus...
Abstract Blood vascular endothelial cells (BECs) control the immune response by regulating blood flow and cell recruitment in lymphoid tissues. However, diversity of BEC their origins during angiogenesis remain unclear. Here we profile transcriptomes from peripheral lymph nodes map phenotypes to vasculature. We identify multiple subsets, including a medullary venous population whose gene signature predicts selective role myeloid (vs lymphocyte) medulla, confirmed videomicroscopy. define five...
Corin is a type II transmembrane serine protease abundantly expressed in the heart. In previous study using transfected 293 cells, we showed that corin converted pro-atrial natriuretic peptide (pro-ANP) to atrial (ANP), suggesting likely pro-ANP convertase. Because other proteases such as thrombin and kallikrein had previously also been shown cleave vitro, it remained demonstrate indeed endogenous convertase cardiomyocytes. this study, examined processing murine cardiac muscle cell line,...
Chemoattractants control lymphocyte recruitment from the blood, contributing to systemic organization of immune system. The G protein-linked receptor GPR15 mediates homing large intestines and skin. Here we show that 9 kDa CC-motif containing cationic polypeptide AP57/colon-derived SUSD2 binding factor (CSBF), encoded by C10orf99 in human 2610528A11Rik mouse, functions as a chemokine ligand for (GPR15L). GPR15L binds attracts GPR15-expressing T cells including lymphocytes colon draining...
P-selectin, an adhesion receptor for leukocytes, is constitutively expressed by megakaryocytes and endothelial cells. Synthesis of P-selectin also increased some inflammatory mediators. We characterized a previously identified κB site (-218GGGGGTGACCCC-207) in the promoter human gene. The was unique that it bound constitutive nuclear protein complexes containing p50 or p52, but not inducible p65. Furthermore, element recombinant p52 homodimers, p65 homodimers. Methylation interference...
P-selectin, an adhesion receptor for leukocytes, is constitutively expressed in megakaryocytes and endothelial cells. Tumor necrosis factor-α (TNF-α) or lipopolysaccharide (LPS) increases synthesis of P-selectin murine but not human To identify potential species-specific conserved mechanisms regulation expression we cloned the 5′-flanking region gene compared its features with those previously reported gene. The genes shared Stat-like, Hox, Ets, GATA, GT-IIC elements. In gene, a GATA element...
P-selectin, an adhesion receptor for leukocytes, is synthesized selectively by megakaryocytes and endothelial cells. We have cloned the 5'-flanking region of human P-selectin gene conducted a preliminary analysis its features. As determined primer extension, RNase protection, anchored polymerase chain reaction cloning, there were multiple transcriptional initiation sites from -95 to -25 nucleotides relative start protein-coding sequence. Transfection bovine aortic cells with serially...
Homing of murine dendritic epidermal T cells (DETCs) from the thymus to skin is regulated by specific trafficking receptors during late embryogenesis. Once in epidermis, Vγ3δ1 TCR DETCs are maintained through self-renewal and participate wound healing. GPR15 an orphan G protein-linked chemoattractant receptor involved recruitment regulatory colon. Here we show that highly expressed on fetal thymic DETC precursors recently recruited DETCs, mediates earliest seeding which occurs at time...
The hematopoietic niche is a supportive microenvironment composed of distinct cell types, including specialized vascular endothelial cells that directly interact with stem and progenitor (HSPCs). molecular factors specify orchestrate HSPC homeostasis remain largely unknown. Using multi-dimensional gene expression chromatin accessibility analyses in zebrafish, we define conserved signature cis-regulatory landscape are unique to sinusoidal the niche. enhancer mutagenesis transcription factor...