- Allergy and Immunology
Clinical Assistant Professor, Pediatrics - Allergy and Clinical Immunology
Residency:Univ of California San FranciscoCA
Internship:Univ of California San FranciscoCA
Fellowship:Stanford University - Allergy and ImmunologyCA
Board Certification: Allergy and Immunology, American Board of Allergy and Immunology (2013)
Board Certification: Pediatrics, American Board of Pediatrics (2010)
Medical Education:UCLA (2007) CA
Molecular and cellular mechanisms of food allergy and food tolerance.
journal of allergy and clinical immunology
2016; 137 (4): 984-997
Ingestion of innocuous antigens, including food proteins, normally results in local and systemic immune nonresponsiveness in a process termed oral tolerance. Oral tolerance to food proteins is likely to be intimately linked to mechanisms that are responsible for gastrointestinal tolerance to large numbers of commensal microbes. Here we review our current understanding of the immune mechanisms responsible for oral tolerance and how perturbations in these mechanisms might promote the loss of oral tolerance and development of food allergies. Roles for the commensal microbiome in promoting oral tolerance and the association of intestinal dysbiosis with food allergy are discussed. Growing evidence supports cutaneous sensitization to food antigens as one possible mechanism leading to the failure to develop or loss of oral tolerance. A goal of immunotherapy for food allergies is to induce sustained desensitization or even true long-term oral tolerance to food allergens through mechanisms that might in part overlap with those associated with the development of natural oral tolerance.
View details for DOI 10.1016/j.jaci.2016.02.004
View details for PubMedID 27059726
Single-cell systems-level analysis of human Toll-like receptor activation defines a chemokine signature in patients with systemic lupus erythematosus
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
2015; 136 (5): 1326-1336
Activation of Toll-like receptors (TLRs) induces inflammatory responses involved in immunity to pathogens and autoimmune pathogenesis, such as in patients with systemic lupus erythematosus (SLE). Although TLRs are differentially expressed across the immune system, a comprehensive analysis of how multiple immune cell subsets respond in a system-wide manner has not been described.We sought to characterize TLR activation across multiple immune cell subsets and subjects, with the goal of establishing a reference framework against which to compare pathologic processes.Peripheral whole-blood samples were stimulated with TLR ligands and analyzed by means of mass cytometry simultaneously for surface marker expression, activation states of intracellular signaling proteins, and cytokine production. We developed a novel data visualization tool to provide an integrated view of TLR signaling networks with single-cell resolution. We studied 17 healthy volunteer donors and 8 patients with newly diagnosed and untreated SLE.Our data revealed the diversity of TLR-induced responses within cell types, with TLR ligand specificity. Subsets of natural killer cells and T cells selectively induced nuclear factor κ light chain enhancer of activated B cells in response to TLR2 ligands. CD14(hi) monocytes exhibited the most polyfunctional cytokine expression patterns, with more than 80 distinct cytokine combinations. Monocytic TLR-induced cytokine patterns were shared among a group of healthy donors, with minimal intraindividual and interindividual variability. Furthermore, autoimmune disease altered baseline cytokine production; newly diagnosed untreated SLE patients shared a distinct monocytic chemokine signature, despite clinical heterogeneity.Mass cytometry defined a systems-level reference framework for human TLR activation, which can be applied to study perturbations in patients with inflammatory diseases, such as SLE.
View details for DOI 10.1016/j.jaci.2015.04.008
View details for Web of Science ID 000364787200023