A5062640985- Gut microbiota and health
- Clostridium difficile and Clostridium perfringens research
- Monoclonal and Polyclonal Antibodies Research
- Reproductive System and Pregnancy
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- Infant Nutrition and Health
- Glycosylation and Glycoproteins Research
- Viral Infections and Outbreaks Research
- Cytokine Signaling Pathways and Interactions
- Macrophage Migration Inhibitory Factor
- Nuclear Receptors and Signaling
- COVID-19 Clinical Research Studies
- Kawasaki Disease and Coronary Complications
- Asthma and respiratory diseases
- Immune cells in cancer
- Bacteriophages and microbial interactions
- Respiratory viral infections research
- HIV/AIDS oral health manifestations
- Reproductive tract infections research
- Epigenetics and DNA Methylation
- COVID-19 Impact on Reproduction
- Pregnancy and Medication Impact
- Parvovirus B19 Infection Studies
University of California, San Francisco
2016-2025
Institut Pasteur
2017
Wellesley College
2013
Louis Stokes Cleveland VA Medical Center
2013
Patients with autoimmune polyendocrinopathy syndrome type 1 (APS-1) caused by autosomal recessive AIRE deficiency produce autoantibodies that neutralize I interferons (IFNs)1,2, conferring a predisposition to life-threatening COVID-19 pneumonia3. Here we report patients NIK or RELB deficiency, specific of autosomal-dominant NF-κB2 also have neutralizing against IFNs and are at higher risk getting pneumonia. In these found only in individuals who heterozygous for variants associated both...
Given the global surge in autoimmune diseases, it is critical to evaluate emerging therapeutic interventions. Despite numerous new targeted immunomodulatory therapies, comprehensive approaches apply and effects of these treatments longitudinally are lacking. Here, we leveraged advances programmable-phage immunoprecipitation methodology explore modulation, or lack thereof, autoantibody profiles, proteome-wide, both health disease. Using a custom set over 730,000 human-derived peptides,...
The human body supports a thriving diversity of microbes which comprise dynamic, ancillary, functional system that synergistically develops in lock-step with physiological development its host. microbiome field has transitioned from cataloging this rich to dissecting molecular mechanisms by microbiomes influence health. Early life trains immune function. Thus, vertically, horizontally, and environmentally acquired their metabolites have the potential shape developmental trajectories...
Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection
While the human fetal immune system defaults to a program of tolerance, there is concurrent need for protective immunity meet antigenic challenges encountered after birth. Activation T cells in utero associated with inflammatory response broad implications health fetus and pregnancy. However, characteristics effector that contribute this process are largely unknown.We analyzed primary lymphoid mucosal tissues performed phenotypic, functional, transcriptional analysis identify...
Maternal asthma status, prenatal exposures, and infant gut microbiota perturbation are associated with heightened risk of atopy in childhood, observations hypothetically linked by intergenerational microbial transmission. Using maternal vaginal (n = 184) paired stool 172) samples, we identify four compositionally functionally distinct Lactobacillus-dominated clusters (VCs) that relate to health exposures serum immunoglobulin E (IgE) status at 1 year. Variance bacteria shared between mother...
The primary goal of the human microbiome initiative has been to increase our understanding structure and function indigenous microbiota their effects on health predisposition disease. Because its clinical importance accessibility for in vivo study, oral biofilm is one best-understood microbial communities associated with body. Studies have shown that there a succession select interactions directs maturation defined community structure, generating formation dental plaque. Although initiating...
Elevated infant fecal concentrations of the bacterial‐derived lipid 12,13‐dihydroxy‐9Z‐octadecenoic acid (12,13‐diHOME) increase risk for childhood atopy and asthma. However, mechanisms by which this contributes to disease development are largely unknown. We hypothesized that macrophages, key both antimicrobial antigen responses, functionally epigenetically modified 12,13‐diHOME leading short‐ long‐term dysfunction with consequences antigenic responses. Macrophages exposed skewed toward...
The Nr4a nuclear hormone receptors are transcriptionally upregulated in response to antigen recognition by the T cell receptor (TCR) thymus and implicated clonal deletion, but mechanisms which they operate not clear. Moreover, their role central tolerance is obscured redundancy among family members reported functions Treg generation maintenance. Here we take advantage of competitive bone marrow chimeras OT-II/RIPmOVA model show that Nr4a1 Nr4a3 essential for upregulation Bcl2l11/BIM thymic...
BackgroundRemoving spores of Clostridium difficile and Bacillus anthracis from skin is challenging because they are resistant to commonly used antimicrobials soap water washing provides only modest efficacy. We hypothesized that hygiene interventions incorporating a sporicidal electrochemically generated hypochlorous acid solution (Vashe®) would reduce the burden on skin. MethodsHands volunteers were inoculated with non-toxigenic C. or B. spore surrogates assess effectiveness Vashe for...
Abstract Escherichia coli is a commensal or pathogenic bacterium that can survive in diverse environments. Adhesion to surfaces essential for E. colonization, and thus it important understand the molecular mechanisms promote this process different niches. Autotransporter proteins are class of cell-surface factor used by adherence. Here we characterized regulation function YeeJ, poorly studied but widespread representative from an emerging autotransporter proteins, inverse autotransporters...
Lymphocytic choriomeningitis virus (LCMV) is a well-studied mammarenavirus that can be fatal in congenital infections. However, our understanding of LCMV and its interactions with human host factors remains incomplete. Here, determinants affecting infection were investigated through genome-wide CRISPR knockout screen A549 cells, lung adenocarcinoma line. We identified validated variety novel play functional role infection. Among these, the sialomucin CD164, heavily glycosylated transmembrane...
Secondary bacterial infections, including ventilator-associated pneumonia (VAP), lead to worse clinical outcomes and increased mortality following viral respiratory infections in patients with coronavirus disease 2019 (COVID-19). Using a combination of tracheal aspirate bulk single-cell RNA sequencing we assessed lower tract immune responses microbiome dynamics 23 COVID-19 patients, 10 whom developed VAP, eight critically ill uninfected controls. At median three days (range: 2-4 days) before...
The prevalence and burden of autoimmune autoantibody mediated disease is increasing worldwide, yet most etiologies remain unclear. Despite numerous new targeted immunomodulatory therapies, comprehensive approaches to apply evaluate the effects these treatments longitudinally are lacking. Here, we leverage advances in programmable-phage immunoprecipitation (PhIP-Seq) methodology explore modulation, or lack thereof, proteome-wide profiles both health disease. We demonstrate that each...
Abstract Secondary bacterial infections, including ventilator-associated pneumonia (VAP), lead to worse clinical outcomes and increased mortality following viral respiratory infections in patients with coronavirus disease 2019 (COVID-19). Using a combination of tracheal aspirate bulk single-cell RNA sequencing (scRNA-seq) we assessed lower tract immune responses microbiome dynamics 28 COVID-19 patients, 15 whom developed VAP, eight critically ill uninfected controls. Two days before VAP...
Abstract Multisystem inflammatory syndrome in children (MIS-C) is a severe, post-infectious sequela of SARS-CoV-2 infection, yet the pathophysiological mechanism connecting infection to broad remains unknown. Here we leveraged large set MIS-C patient samples (n=199) identify distinct host proteins that are differentially targeted by autoantibodies relative matched controls. We identified an autoreactive epitope within SNX8, protein expressed primarily immune cells which regulates antiviral...
Autoimmunity is characterized by loss of tolerance to tissue-specific as well systemic antigens, resulting in complex autoantibody landscapes. Here, we introduce and extensively validate the performance characteristics a murine proteome-wide library for phage display immunoprecipitation sequencing (PhIP-seq) profiling mouse autoantibodies. This was validated using 7 genetically distinct lines across spectrum autoreactivity. Mice deficient antibody production (Rag2-/- μMT) were used model...
Autoimmunity is characterized by loss of tolerance to tissue-specific as well systemic antigens, resulting in complex autoantibody landscapes. Here, we introduce and extensively validate the performance characteristics a murine proteome-wide library for phage display immunoprecipitation sequencing (PhIP-seq), profile mouse autoantibodies. This system were validated using seven genetic models across spectrum autoreactivity. Mice deficient antibody production (
Abstract Although deletion of self-reactive thymocytes and their diversion into regulatory T cell (Treg) lineage are critical for immune tolerance homeostasis, the molecular pathways that link antigen recognition to these fates incompletely understood. The Nr4a nuclear hormone receptors transcriptionally upregulated in response TCR signaling thymus implicated both diversion, but mechanisms by which they operate not clear. Redundancy among family members requirement Treg generation...
SUMMARY Complications from preterm birth are the leading cause of global mortality in children under age five 1,2 . Spontaneous labor is most common delivery and associated with a breakdown maternal-fetal tolerance 3–5 However, current understanding role autoantibodies this process has been limited to handful examples pathogenic antibodies that occur pregnancy complications 6–14 Here, we employ proteome-wide autoantibody profiling via phage display immunoprecipitation sequencing (PhIP-seq)...