A5060950716- Tuberculosis Research and Epidemiology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- T-cell and B-cell Immunology
- Mycobacterium research and diagnosis
- RNA Interference and Gene Delivery
- vaccines and immunoinformatics approaches
- Sepsis Diagnosis and Treatment
- Immunodeficiency and Autoimmune Disorders
- Immune Response and Inflammation
- Infectious Diseases and Tuberculosis
- Monoclonal and Polyclonal Antibodies Research
- Cytomegalovirus and herpesvirus research
- CAR-T cell therapy research
- Tryptophan and brain disorders
- Neutropenia and Cancer Infections
- Health Sciences Research and Education
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Antibiotic Resistance in Bacteria
- Viral gastroenteritis research and epidemiology
- Climate Change and Health Impacts
- Simulation-Based Education in Healthcare
- Thermal Regulation in Medicine
- Respiratory viral infections research
- Pneumocystis jirovecii pneumonia detection and treatment
Oregon Health & Science University
2012-2025
University of Virginia
2022-2025
Boise State University
2025
Viti (United States)
2018
Portland VA Medical Center
2007
Control of infection with Mycobacterium tuberculosis (Mtb) requires Th1-type immunity, which CD8+ T cells play a unique role. High frequency Mtb-reactive are present in both Mtb-infected and uninfected humans. We show by limiting dilution analysis that nonclassically restricted universally present, but predominate Mtb-uninfected individuals. Interestingly, these expressed the Vα7.2 T-cell receptor (TCR), were nonclassical MHC (HLA-Ib) molecule MR1, activated transporter associated antigen...
A diverse array of microbial metabolites binds to MR1 and selectively activates MR1-restricted T cells.
CD8(+) T cells are essential for host defense to intracellular bacterial pathogens such as Mycobacterium tuberculosis (Mtb), Salmonella species, and Listeria monocytogenes, yet the repertoire dominance pattern of human CD8 antigens these remains poorly characterized. Tuberculosis (TB), disease caused by Mtb infection, one leading causes infectious morbidity mortality worldwide is most frequent opportunistic infection in individuals with HIV/AIDS. Therefore, we undertook this study define...
The immunologic events surrounding primary Mycobacterium tuberculosis infection and development of remain controversial. Young children who develop do so quickly after first exposure, thus permitting study immune response to disease. We hypothesized that M. tuberculosis-specific CD8(+) T cells are generated in high bacillary loads occurring during tuberculosis.To determine if among healthy exposed with tuberculosis.Enzyme-linked immunosorbent spot assays were used measure IFN-γ production...
Despite widespread use of the Bacillus Calmette-Guerin vaccine, tuberculosis, caused by infection with Mycobacterium remains a leading cause morbidity and mortality worldwide. As CD8+ T cells are critical to tuberculosis host defense phase 2b vaccine trial modified vaccinia Ankara expressing Ag85a that failed demonstrate efficacy, also induce cell response, an effective may need cells. However, little is known about CD8, as compared CD4, antigens in tuberculosis. Herein, we report results...
Identification of CD8+ T cell antigens/epitopes expressed by human pathogens with large genomes is especially challenging, yet necessary for vaccine development. Immunity to tuberculosis, a leading cause mortality worldwide, requires immunity, the repertoire CD8 remains undefined. We used integrated computational and proteomic approaches screen 10% Mycobacterium tuberculosis (Mtb) proteome Mtb antigens. designed weighting schema based upon Multiple Attribute Decision Making:framework select...
HLA-E is a non-conventional MHC Class I molecule that has been recently demonstrated to present pathogen-derived ligands, resulting in the TCR-dependent activation of αβ CD8+ T cells. The goal this study was characterize ligandome displayed by following infection with Mycobacterium tuberculosis (Mtb) using an in-depth mass spectrometry approach. Here we identified 28 Mtb ligands derived from 13 different source proteins, including Esx family proteins. When tested for activity cells isolated...
Rationale Biomarkers associated with response to therapy in tuberculosis could have broad clinical utility. We postulated that the frequency of Mycobacterium (Mtb) specific CD8+ T cells, by virtue detecting intracellular infection, be a surrogate marker and would decrease during effective antituberculosis treatment. Objectives: sought determine relationship Mtb CD4+ cells duration Materials Methods performed prospective cohort study, enrolling between June 2008 August 2010, HIV-uninfected...
Infection with Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis, remains a global health concern. Both classically and non-classically restricted cytotoxic CD8+ T cells are important to control of Mtb infection. We others have demonstrated non-classical MHC I molecule HLA-E can present pathogen-derived peptides cells. In this manuscript, we identified antigen recognized by an HLA-E-restricted cell clone isolated from latently infected individual as peptide protein,...
Abstract MR1-restricted T cells have been implicated in microbial infections, sterile inflammation, wound healing and cancer. Similar to other antigen presentation molecules, evidence supports multiple, complementary MR1 pathways. To investigate ligand exchange pathways for MR1, we used monomers tetramers loaded with 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU) deliver the antigen. Using MR1-deficient reconstituted wild-type or molecules that cannot bind 5-OP-RU, show of...
Neonatal sepsis is a leading cause of childhood mortality. Understanding immune cell development can inform strategies to combat this. MR1-restricted T (MR1T) cells be defined by their recognition small molecules derived from microbes, self, and drug drug-like molecules, presented the MHC class 1-related molecule (MR1). In healthy adults, majority MR1T express an invariant α-chain; TRAV1-2/TRAJ33/12/20 are referred as mucosal-associated (MAIT) cells. isolated cord blood (CB) demonstrate more...
Neonatal sepsis is a leading cause of childhood mortality. Understanding immune cell development can inform strategies to combat this. MR1-restricted T (MR1T) cells be defined by their recognition small molecules derived from microbes, self, and drug drug-like molecules, presented the MHC class 1-related molecule (MR1). In healthy adults, majority MR1T express an invariant α-chain; TRAV1-2/TRAJ33/12/20 are referred as mucosal-associated (MAIT) cells. isolated cord blood (CB) demonstrate more...
Background: There has been a push toward degree advancement throughout respiratory care (RC), with many academic institutions creating graduate-level programs. However, practitioners are apprehensive about advancing their degrees past the entry-into-practice level. Little research exists regarding benefits of in RC. Methods: A web-based survey was developed to identify perceived completing master's science RC (MSRC) program. Graduates from 7 MSRC programs were asked how efficacious program...
MR1-restricted T (MR1T) cells are defined by their recognition of metabolite antigens presented the monomorphic MHC class 1-related molecule, MR1, most highly conserved I related molecule in mammalian species. Mucosal-associated invariant (MAIT) predominant subset MR1T expressing an TCR -chain, TRAV1-2. These comprise a cell that recognizes and mediates host immune responses to broad array microbial pathogens, including Mycobacterium tuberculosis. Here, we sought characterize development...
MR1 presents vitamin B-related metabolites to mucosal associated invariant T (MAIT) cells, which are characterized, in part, by the TRAV1-2
Sepsis is the leading cause of global death with highest burden found in sub-Saharan Africa (sSA). The Universal Vital Assessment (UVA) score a validated resource-appropriate clinical tool to identify hospitalized patients sSA who are at risk in-hospital mortality. Whether decrease UVA over 6 hours resuscitation from sepsis associated improved outcomes unknown. We aimed determine (1) association between 6-hour and mortality, (2) if admission was analyzed data participants severe aged ≥14...
MR1-restricted T (MR1T) cells recognize microbial small molecule metabolites presented on the MHC Class I-like MR1 and have been implicated in early effector responses to infection. As a result, there is considerable interest identifying chemical properties of metabolite ligands that permit recognition by MR1T cells, for consideration therapeutic or vaccine applications. Here, we made modifications known evaluate effect cell activation. Specifically, modified 6,7-dimethyl-8-D-ribityllumazine...
Abstract MR1-restricted T (MR1T) cells are defined by their recognition of metabolite antigens presented the monomorphic MHC class 1-related molecule, MR1, most highly conserved I related molecule in mammalian species. Mucosal-associated invariant (MAIT) predominant subset MR1T expressing an TCR α-chain, TRAV1-2. These comprise a cell that recognizes and mediates host immune responses to broad array microbial pathogens, including Mycobacterium tuberculosis . Here, we sought characterize...
Introduction Sub-Saharan Africa shoulders the highest burden of global sepsis and associated mortality. In high HIV tuberculosis (TB) prevalent settings such as sub-Saharan Africa, TB is leading cause sepsis. However, anti-TB therapy often delayed may not achieve adequate blood concentrations in patients with Accordingly, this multisite randomised clinical trial aims to determine whether immediate and/or increased dose improves 28-day mortality for participants Tanzania or Uganda. Methods...