A5053493275- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Diabetes and associated disorders
- Advanced Proteomics Techniques and Applications
- Eosinophilic Esophagitis
- Mass Spectrometry Techniques and Applications
- IL-33, ST2, and ILC Pathways
- Metabolomics and Mass Spectrometry Studies
- Eosinophilic Disorders and Syndromes
- Genetics, Bioinformatics, and Biomedical Research
- Invertebrate Immune Response Mechanisms
- Immunotherapy and Immune Responses
- Cancer Genomics and Diagnostics
- Herpesvirus Infections and Treatments
- Food Allergy and Anaphylaxis Research
- Genomics and Phylogenetic Studies
- Pediatric Hepatobiliary Diseases and Treatments
- Gene expression and cancer classification
- Thermoregulation and physiological responses
- Machine Learning in Bioinformatics
- Advanced Biosensing Techniques and Applications
- Liver Disease Diagnosis and Treatment
- Celiac Disease Research and Management
- Viral-associated cancers and disorders
- Infrared Thermography in Medicine
Benaroya Research Institute
2021-2025
University of California, Riverside
2024
Virginia Mason Medical Center
2023-2024
Seattle University
2023
University of Washington
2014-2018
The ultimate aim of proteomics is to fully identify and quantify the entire complement proteins post-translational modifications in biological samples interest. For last 15 years, liquid chromatography-tandem mass spectrometry (LC-MS/MS) data-dependent acquisition (DDA) mode has been standard for when sampling breadth discovery were main objectives; multiple reaction monitoring (MRM) LC-MS/MS targeted precise quantification, reproducibility, validation objectives. Recently, improvements...
Cancers arise from successive rounds of mutation and selection, generating clonal populations that vary in size, mutational content drug responsiveness. Ascertaining the composition a tumor is therefore important both for prognosis therapy. Mutation counts frequencies resulting next-generation sequencing (NGS) potentially reflect tumor's composition; however, deconvolving NGS data to infer structure presents major challenge. We propose generative model derived multiple subsections single...
Permutational analysis of the immune system reveals advanced aging in individuals with Down syndrome and type 1 diabetes.
CD4 + CD25 hi CD127 lo/− FOXP3 regulatory T cells (T regs ) play a key role in preventing autoimmunity. In autoimmune type 1 diabetes (T1D), adoptive transfer of autologous polyclonal has been shown to be safe adults phase clinical trials. We explored factors contributing efficacy expanded (expT randomized 2 multi-center, double-blind, trial (Sanford/Lisata Therapeutics T-Rex trial, ClinicalTrials.gov NCT02691247). One hundred ten treated children and adolescents with new-onset T1D were...
Regulatory T cells (Tregs) suppress the activation and subsequent effector functions of CD4 (Teffs). However, molecular mechanisms that enforce Treg-mediated suppression in Teff are unclear. We found Tregs suppressed activation-induced global protein synthesis Teffs prior to cell division. analyzed genome-wide changes transcriptome translatome activated Teffs. show mRNAs encoding for machinery regulated at level translation by Tregs. specifically inhibiting mTORC1-mediated control through...
Kaposi's Sarcoma associated Herpesvirus (KSHV), an oncogenic, human gamma-herpesvirus, is the etiological agent of most common tumor AIDS patients world-wide. KSHV predominantly latent in main KS cell, spindle a cell endothelial origin. modulates numerous host cell-signaling pathways to activate cells including major metabolic involved lipid metabolism. To identify underlying cellular mechanisms alteration signaling and activation, we identified changes proteome, phosphoproteome...
Recruitment of regulatory T cells (T regs ) to tumors is a hallmark cancer progression. Tumor-derived factors, such as the cytokine thymic stromal lymphopoietin (TSLP), can influence reg function in tumors. In our study, we identified subset expressing receptor for TSLP (TSLPR + that were increased colorectal humans and mice largely absent adjacent normal colon. This was also found peripheral blood patients with colon but not healthy control subjects. Mechanistically, this coexpressed...
Vaccination leads to rapid expansion of antigen-specific T cells within in the first few days. However, understanding transcriptomic changes and fates upon vaccination remains limited. Here, we investigate fate memory CD4+ reactivation recombinant zoster vaccine for shingles at cellular transcriptional levels. We show that glycoprotein E-specific respond strongly, their frequencies remain high, they retain markers cell activation one year following vaccination. Memory with most dominant TCR...
Abstract Eosinophilic esophagitis (EoE) is an allergic inflammatory disease of the esophagus that occurs in both children and adults. Previous studies affected tissue from pediatric cohorts have identified prominent signatures eosinophilia type 2 inflammation. However, details immune response adults with EoE are still being elucidated. To determine whether shares profiles those observed children, we performed RNA sequencing paired human esophageal biopsies blood samples or gastroesophageal...
Human islet antigen reactive CD4+ memory T cells (IAR cells) play a key role in the pathogenesis of autoimmune type 1 diabetes (T1D). Using single-cell RNA sequencing (scRNA-Seq) to identify cell receptors (TCRs) IAR cells, we have identified class TCRs that share TCRα chains between individuals ("public" chains). We isolated from blood healthy, new-onset T1D and established donors using multiplexed CD154 enrichment paired TCRαβ sequences 2767 individual cells. More than quarter shared TCR...
Variation in the preservation of β cell function clinical trials type 1 diabetes (T1D) has emphasized need to define biomarkers predict treatment response. The T1DAL trial targeted T cells with alefacept (LFA-3-Ig) and demonstrated C-peptide approximately 30% new-onset T1D individuals. We analyzed islet antigen-reactive (IAR) CD4+ PBMC samples collected prior from alefacept- placebo-treated individuals using flow cytometry single-cell RNA sequencing. IAR at baseline had heterogeneous...
11077 Background: Cancers arise from successive rounds of mutation and selection, generating clonal populations that vary in size, mutational content drug responsiveness. Ascertaining the composition a tumor is therefore important both for prognosis therapy. Methods: Mutation counts frequencies resulting next-generation sequencing (NGS) potentially reflect tumor's composition; however, deconvolving NGS data to infer structure presents major challenge. We propose generative model derived...
Therapeutics that inhibit IL-6 at different points in its signaling pathway are clinical use, yet whether the immunological effects of these interventions differ based on their molecular target is unknown. We performed short-term individuals with type 1 diabetes using anti-IL-6 (siltuximab) or receptor (IL-6R; tocilizumab) therapies and investigated impact this vivo blockade T cell fate function. Immune outcomes were influenced by therapeutic intervention (IL-6 versus IL-6R) peak drug...
ABSTRACT Background Eosinophilic esophagitis (EoE) is a chronic, type 2 inflammatory disease that increasing in incidence and has substantial morbidity. Despite being clinically defined as food allergy, the molecular details of antigen presentation recognition by immune system are unknown. Objective The objective this study was to identify characterize basis milk T cell patient with EoE allergy. Methods Milk-expanded TCR clonotypes were identified using ex vivo stimulation followed single...
In data independent acquisition (DIA) mass spectrometry, precursor scans are interleaved with wide-window fragmentation scans, resulting in complex spectra containing multiple coeluting peptide species. this setting, detecting the isotope distribution profiles of intact peptides can be a critical initial step accurate detection and quantification. This peak is particularly challenging when peaks associated two different species overlap-or interfere-with one another. We propose regression...
Abstract The thymus is an important site for the establishment of appropriate immune response through positive and negative selection developing T cells. During selection, cells interact with cortical medullary thymic epithelial (TECs), termed cTECs mTECs, respectively. Using a Foxn1Cre+/-SKIfl/fl mouse model, we found that TEC-specific deletion SKI reduced mTEC compartment in tissue-restricted Ag expression mTECs was altered. This decrease area led to CD4 thymocyte cellularity; however,...
Temperature stress is one of the major limiting environmental factors that negatively impact global crop yields.
SUMMARY Increased protein synthesis is a hallmark of lymphocyte activation. Regulatory T cells (Tregs) suppress the activation and subsequent effector functions CD4 (Teffs). However, molecular mechanisms that enforce Treg-mediated suppression in Teff are not fully clear. Control by Tregs has largely been defined at transcriptional level, which does reflect changes post-transcriptional control. We found suppressed activation-induced global Teffs prior to cell division. analyzed genome-wide...
Abstract Cbl-b is a negative regulator of T cell activation, and in murine models, lack Cblb results resistance effector (Teff) cells to regulatory (Treg) cells, feature many autoimmune diseases. Here, we used trackable gene editing approaches knock out CBLB primary human CD4+ cells. We found that CBLB-knockout (CBLB-KO) were hyperproliferative produced excessive amounts IL-2. CBLB-KO resistant Treg suppression vitro, which was partially reversed by blockade RNA-sequencing puromycin...
Abstract Type 1 diabetes (T1D) is an autoimmune disease marked by immune destruction of insulin-producing β-cells the pancreas. In effort to halt progression, autologous polyclonal expanded regulatory T cells (expTregs) were adoptively transferred into adolescents with recent-onset T1D (Sanford/Lisata Therapeutics Trex Phase 2 clinical trial, NCT02691247). Overall, expTreg therapy (1–24×10 6cells/kg) did not preserve residual β-cell function, as measured change in insulin C-peptide AUC-mean...