A5019157015- Proteoglycans and glycosaminoglycans research
- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Immune Cell Function and Interaction
- Fibroblast Growth Factor Research
- T-cell and B-cell Immunology
- Diabetes and associated disorders
- CAR-T cell therapy research
- Phytoestrogen effects and research
- Hops Chemistry and Applications
- Hemostasis and retained surgical items
- Connective tissue disorders research
- Tryptophan and brain disorders
- Immunodeficiency and Autoimmune Disorders
- Protease and Inhibitor Mechanisms
- Adenosine and Purinergic Signaling
University of California, San Francisco
2024
Joslin Diabetes Center
2017-2020
Harvard University
2017-2020
Lund University
2012-2018
Boston University
2012
Matrix Research (United States)
2012
Radboud University Nijmegen
2012
Skåne University Hospital
2012
Extracellular matrix, either produced by cancer cells or cancer-associated fibroblasts, influences angiogenesis, invasion, and metastasis. Chondroitin/dermatan sulfate (CS/DS) proteoglycans, which occur both in the matrix at cell surface, play important roles these processes. The unique feature that distinguishes DS from CS is presence of iduronic acid (IdoA) DS. Here, we report CS/DS increased five-fold human biopsies esophagus squamous carcinoma (ESCC), an aggressive tumor with poor...
T cells express clonotypic cell receptors (TCRs) that recognize peptide antigens in the context of class I or II MHC molecules (pMHCI/II). These receptor modules associate with three signaling (CD3γε, δε, and ζζ) work concert a coreceptor module (either CD8 CD4) to drive activation response pMHCI/II. Here, we describe first-generation biomimetic five-module chimeric antigen (5MCAR). We show 1) built ectodomains pMHCII assemble CD3 into complexes redirect cytotoxic lymphocyte (CTL)...
Dermatan sulfate epimerase 2 (DS-epi2), together with its homolog DS-epi1, transform glucuronic acid into iduronic in DS polysaccharide chains. Iduronic gives increased chain flexibility and promotes protein binding. DS-epi2 is ubiquitously expressed the predominant brain. Here, we report generation initial characterization of null mice. DS-epi2-deficient mice showed no anatomical, histological or morphological abnormalities. The body weights lengths mutated wild-type littermates were...
Aortic smooth muscle cells produce chondroitin/dermatan sulfate (CS/DS) proteoglycans that regulate extracellular matrix organization and cell behavior in normal pathological conditions. A unique feature of CS/DS is the presence iduronic acid (IdoA), catalyzed by two DS epimerases. Functional ablation DS-epi1, main epimerase these cells, resulted a major reduction IdoA both on surface secreted proteoglycans. Downregulation led to delayed ability re-populate wounded areas due loss directional...
During the biosynthesis of chondroitin/dermatan sulfate (CS/DS), a variable fraction glucuronic acid is converted to iduronic through activities two epimerases, dermatan epimerases 1 (DS-epi1) and 2 (DS-epi2). Previous in vitro studies indicated that without association with other enzymes, DS-epi1 activity produces structures have only few adjacent units. In vivo, concomitant epimerization, 4-O-sulfotransferase (D4ST1) sulfates GalNAc acid. This sulfation facilitates enables formation long...
Dysfunctional T cells can mediate autoimmunity, but the inaccessibility of autoimmune tissues and rarity in blood hinder their study. We describe a method to enrich harvest vivo by using biomaterial scaffold loaded with protein antigens. In model antigen systems, we found that antigen-specific become enriched within scaffolds containing cognate When lysates from an insulin-producing β-cell line were implanted subcutaneously diabetes–prone NOD mice, β-cell–reactive homed these became...
Abstract Regulation of T cell signaling is paramount to mount an appropriate immune response and protect the host from pathophysiology. Here, we study impact on CD8+ cells in monogenic inborn error immunity patients exhibiting dysregulated signal 3 (cytokine signaling) pathways resulting STAT3 gain- or loss-of-function variants (STAT3 GOF LOF). Using high dimensional profiling, demonstrate increased expression ectoenzyme, CD39, which hydrolyzes extracellular ATP, patient cells. Moreover, two...
Signal transduction downstream of activating stimuli controls CD8+ T cell biology, however these external inputs can become uncoupled from transcriptional regulation in Primary Immune Regulatory Disorders (PIRDs). Gain-of-function (GOF) variants STAT3 amplify cytokine signaling and cause a severe PIRD characterized by early onset autoimmunity, lymphoproliferation, recurrent infections, immune dysregulation. In both primary human mouse models GOF, cells have been implicated as pathogenic...
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<p>PDF file - 246K</p>
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<div>Abstract<p>Extracellular matrix, either produced by cancer cells or cancer-associated fibroblasts, influences angiogenesis, invasion, and metastasis. Chondroitin/dermatan sulfate (CS/DS) proteoglycans, which occur both in the matrix at cell surface, play important roles these processes. The unique feature that distinguishes DS from CS is presence of iduronic acid (IdoA) DS. Here, we report CS/DS increased five-fold human biopsies esophagus squamous carcinoma (ESCC), an...
<div>Abstract<p>Extracellular matrix, either produced by cancer cells or cancer-associated fibroblasts, influences angiogenesis, invasion, and metastasis. Chondroitin/dermatan sulfate (CS/DS) proteoglycans, which occur both in the matrix at cell surface, play important roles these processes. The unique feature that distinguishes DS from CS is presence of iduronic acid (IdoA) DS. Here, we report CS/DS increased five-fold human biopsies esophagus squamous carcinoma (ESCC), an...
Abstract T cells express clonotypic cell receptors (TCRs) that recognize peptide antigens in the context of class I or II MHC molecules (pMHCI/II). These receptor modules associate with three signaling (CD3γε, δε, and ζζ), work concert a coreceptor module (either CD8 CD4), to drive activation response pMHCI/II. Here we describe first generation biomimetic 5-module chimeric antigen ( 5M CAR). We show that: (i) built ectodomains pMHCII assemble CD3 into complexes redirect cytotoxic lymphocyte...