A5070426940- Inflammatory Bowel Disease
- Advanced Biosensing Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Systemic Lupus Erythematosus Research
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Immune Cell Function and Interaction
- Immune Response and Inflammation
- Immunodeficiency and Autoimmune Disorders
- Immunotherapy and Immune Responses
- NF-κB Signaling Pathways
- Microscopic Colitis
- IL-33, ST2, and ILC Pathways
- Cytokine Signaling Pathways and Interactions
- Psoriasis: Treatment and Pathogenesis
- Pregnancy and Medication Impact
- Cell death mechanisms and regulation
- Gut microbiota and health
- Advanced biosensing and bioanalysis techniques
- Immune cells in cancer
- Esophageal Cancer Research and Treatment
- Inflammasome and immune disorders
- Autophagy in Disease and Therapy
- Reproductive System and Pregnancy
University of California, San Francisco
2015-2024
University of Southern California
2022
Kaiser Permanente
2018
Stanford University
2006-2010
Palo Alto University
2006-2008
Stanford Medicine
2006
Pediatrics and Genetics
2006
National Institutes of Health
2002-2004
Georgetown University
2004
Georgetown University Medical Center
2004
Ulcerative colitis (UC) is driven by immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) an anti-integrin antibody that effective for treating UC. VDZ known to inhibit lymphocyte trafficking the intestine, but its broader effects on other cell subsets are less defined. To identify inflammatory cells contribute affected VDZ, we perform single-cell transcriptomic proteomic analyses of peripheral blood colonic biopsies healthy controls patients with UC or therapies....
Abstract The IL-23/IL-17 pathway plays an important role in chronic inflammatory diseases, including bowel disease. In disease, intestinal epithelial cells are source of chemokines that recruit cells. We examined the effect IL-17 on chemokine expression HT-29 colonic strongly repressed TNF-α-stimulated CXCL10, CXCL11, and CCL5, but synergized with TNF-α for induction CXCL8, CXCL1, CCL20 mRNAs. For inhibited promoter activity had no mRNA stability. contrast, slightly decreased stabilized its...
In this paper, we report an experimental study of electrokinetic transport and separation double-stranded deoxyribonucleic acid (dsDNA) oligonucleotides in custom-fabricated fused-silica nanochannels filled with a gel-free sodium borate aqueous buffer. Mixtures fluorescently labeled dsDNA molecules the range 10−100 base pair (bp), fluorescein, fluorescein-12-UTP (UTP) were separated less than 120 s channels depth ranging from 40 to 1560 nm. We varied channel background buffer concentration...
A20 (TNFAIP3) and ABIN-1 (TNIP1) are candidate susceptibility genes for inflammatory bowel disease other autoimmune or diseases, but it is unclear how these proteins interact in vivo to prevent disease. Here we show that intestinal epithelial cell (IEC)-specific deletion of either alone leads negligible IEC loss, whereas simultaneous both rapid death mouse lethality. Deletion from enteroids causes spontaneous the absence microbes hematopoietic cells. Studies with reveal synergistically...
Anti-TNF antibodies are effective for treating patients with inflammatory bowel disease (IBD), but many fail to respond anti-TNF therapy, highlighting the importance of TNF-independent disease. We previously demonstrated that acute deletion 2 IBD susceptibility genes, A20 (Tnfaip3) and Abin-1 (Tnip1), in intestinal epithelial cells (IECs) sensitized mice both TNF-dependent death. Here we show IEC death after was rescued by germ-free derivation or MyD88, while Trif provided only partial...
Background Colitis caused by checkpoint inhibitors (CPI) is frequent and treated with empiric steroids, but CPI colitis mechanisms in steroid-experienced or refractory disease are unclear. Methods Using colon biopsies blood from predominantly patients, we performed multiplexed single-cell transcriptomics proteomics to nominate contributing populations. Results showed enrichment of CD4 + resident memory (RM) T cells addition CD8 RM cytotoxic cells. Matching cell receptor (TCR) clonotypes...
Inflammatory bowel disease (IBD) treatments and pregnancy can independently modulate immune responses, but the combined effects on SARS-CoV-2 vaccine-induced immunity are poorly understood. This study explores efficacy of vaccination placental antibody transfer among pregnant women with IBD biologic therapies. observational included without from PIANO PREVENT-COVID studies their neonates. We assessed anti-SARS-CoV-2 neutralizing titers (NT50) in maternal cord blood post-vaccination using a...
Abstract Objective Th17 cells (interleukin‐17 [IL‐17]–secreting T helper cells) have been implicated in the pathogenesis of rheumatoid arthritis and other autoimmune diseases, but soluble factors that influence human differentiation yet to be fully elucidated. This study was undertaken investigate hypothesis cytokines secreted by peripheral blood mononuclear (PBMCs) response a subset Toll‐like receptor (TLR) ligands would polarization. Methods Supernatants from PBMCs treated with panel TLR...
Resident microbes in skin and gut predominantly impact local immune cell function during homeostasis. However, colitis-associated neutrophilic disorders suggest possible breakdown of this compartmentalization with disease. Using a model wherein neonatal colonization by Staphylococcus epidermidis facilitates generation commensal-specific tolerance CD4+ regulatory T cells (Tregs), we ask whether response is perturbed inflammation. Chemically induced colitis accompanied intestinal expansion S....
In this study, we demonstrate that the E3 ubiquitin ligase gene related to anergy in lymphocytes (GRAIL) is expressed quiescent naive mouse and human CD4 T cells has a functional role inhibiting cell proliferation. Following TCR engagement, CD28 costimulation results expression of IL-2 whose signaling through its receptor activates Akt-mammalian target rapamycin (mTOR) pathway. Activation mTOR allows selective mRNA translation, including epistatic regulator GRAIL, Otubain-1 (Otub1),...
Antigen-specific CD4(+) T cells are implicated in the autoimmune disease systemic lupus erythematosus (SLE), but little is known about peptide antigens that they recognize and their precise function disease. We generated a series of MHC class II tetramers I-E(k)-containing peptides from spliceosomal protein U1-70 specifically stain distinct T-cell populations MRL/lpr mice. The an epitope differing only by presence or absence single phosphate residue at position serine(140). frequency...
Infants exposed to combination therapy with anti-tumor necrosis factor (anti-TNF) agents and thiopurines may exhibit increased infections at 1 year of age compared unexposed infants. We hypothesized that this risk infection is due abnormal development the newborn immune system.We immunophenotyped B-cell T-cell subsets using multiparameter flow cytometry in 1-year-old infants whose mothers were therapeutic for IBD. analyzed samples from infliximab (IFX) or adalimumab (ADA) monotherapy...
Screening for heavy-atom derivatives remains a time-consuming and cumbersome process that often results in non-isomorphous whose phases cannot be combined. Using lysozyme FcγRIII receptor crystals as test cases, an improved soaking method the generation of conventional has been developed. The is based on compounds very brief time at near-saturation concentrations. Compared with current method, which takes days to achieve derivatization, quick-soak completes derivatization within 10 min 2 h....
Abstract NKG2D recognizes multiple diverse ligands. Despite recent efforts in determining the crystal structures of NKG2D-ligand complexes, principle governing this receptor-ligand recognition and hence criteria for identifying unknown ligands remain central issues to be resolved. Here we compared molecular between three known ligands, UL16 binding protein (ULBP), MHC class I-like molecule, retinoic acid early inducible gene as observed ligand-complexed structures. The comparison shows that...
We have utilized a computational structure-based approach to identify nonpeptidic small organic compounds that bind human leukocyte antigen (HLA) DR1301 molecule (HLA-DR1301 or DR1301) and block the presentation of myelin basic protein peptide 152−165 (MBP 152−165) T cells. A three-dimensional (3D) structure was derived by homology modeling followed extensive molecular dynamics simulation for structural refinement. Computational database searching performed small-molecule candidates from...
Anti-α4β7 (Vedolizumab) treats inflammatory bowel disease (IBD) by blocking the interaction between integrin α4β7 on leukocytes and mucosal addressin cell-adhesion molecule-1 (MAdCAM-1) gut endothelium. Women with IBD often require continuing biologic therapy during pregnancy to avoid flare. To date, there have been no reports of an increase in adverse events Vedolizumab use pregnancy. Notably, integrins play a major role human placental development It is unknown whether disrupts cell...