- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Protein Tyrosine Phosphatases
- Adrenal Hormones and Disorders
- Appendicitis Diagnosis and Management
- Antifungal resistance and susceptibility
- Indoor Air Quality and Microbial Exposure
- Gallbladder and Bile Duct Disorders
- Complement system in diseases
- Potassium and Related Disorders
- SARS-CoV-2 detection and testing
- Systemic Lupus Erythematosus Research
- Intraperitoneal and Appendiceal Malignancies
- Acute Myeloid Leukemia Research
- Asian Studies and History
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Acute Lymphoblastic Leukemia research
- PI3K/AKT/mTOR signaling in cancer
- Chronic Myeloid Leukemia Treatments
- Ocular Infections and Treatments
- Philippine History and Culture
- Gastroesophageal reflux and treatments
University of Minnesota
2012-2024
University of Minnesota Medical Center
2011-2024
University of the Philippines Diliman
2023
Harvey Mudd College
2022
Swedish Medical Center
2018-2020
Emory University
2013-2019
Swedish Family Medicine Residency - Cherry Hill
2016
In response to infection, naïve CD4+ T cells differentiate into two subpopulations: follicular helper (TFH) cells, which support B cell antibody production, and non-TFH enhance innate immune functions. Interleukin-2 (IL-2), the major cytokine produced by plays an important role in developmental divergence of these populations. However, relationship between IL-2 production fate determination remains unclear. Using reporter mice, we found that differential defined precursors fated for...
B cell tolerance to self-antigen is critical preventing antibody-mediated autoimmunity. Previous work using antigen receptor transgenic animals suggested that self-antigen-specific cells are either deleted from the repertoire, enter a state of diminished function termed anergy, or ignorant presence self-antigen. These mechanisms have not been assessed in normal polyclonal repertoire because an inability detect rare antigen-specific cells. Using novel detection and enrichment strategy assess...
Abstract B cells provide humoral immunity by differentiating into antibody-secreting plasma cells, a process that requires cellular division and is linked to DNA hypomethylation. Conversely, little known about how de novo deposition of methylation affects cell fate function. Here we show genetic deletion the methyltransferases Dnmt3a Dnmt3b (Dnmt3-deficient) in mouse results normal development maturation, but increased activation expansion germinal center populations upon immunization. Gene...
The activation of thymic B cells is critical for their licensing as antigen presenting and resulting ability to mediate T cell central tolerance. processes leading are still not fully understood. By comparing activated Peyer's patch at steady state, we found that starts during the neonatal period characterized by TCR/CD40-dependent activation, followed immunoglobulin class switch recombination (CSR) without forming germinal centers. Transcriptional analysis also demonstrated a strong...
Rheumatoid arthritis develops in association with a defect peripheral CD4(+) T cell homeostasis. lymphopenia has also been shown to be barrier clonal anergy induction. We therefore explored the relationship between induction and avoidance of autoimmune by tracking fate glucose-6-phosphate isomerase (GPI)-reactive cells setting selective lymphopenia. recognition self-GPI peptide/MHC class II complexes normal murine hosts did not lead instead caused those develop Folate receptor 4(hi)CD73(hi)...
Abstract A robust primary immune response has been correlated with the precursor number of antigen-specific T cells, as identified using peptide MHCII tetramers. However, these tetramers identify only highest-affinity cells. Here we show entire CD4+ T-cell repertoire, inclusive low-affinity cells missed by tetramers, a receptor (TCR) signalling reporter and micropipette assay to quantify naive precursors expanded populations. In vivo limiting dilution assays reveal hundreds more than...
Type I and III interferons (IFNs) are robustly induced during infections protect cells against viral infection. Both type IFNs also produced at low levels in the thymus steady state; however, their role T cell development immune tolerance is unclear. Here, we found that both were constitutively by a very small number of AIRE + murine thymic epithelial cells, independent microbial stimulation. Antigen-presenting highly responsive to IFNs, required for activation maturation 1 conventional...
Abstract T-cell central tolerance is controlled by thymocyte TCR recognition of self-peptides presented thymic APCs. While epithelial cells are essential for tolerance, a variety other traditional APCs also play critical roles in selection. Similar to how peripheral require activation become effective, tolerogenic. Recent studies have identified IFNs as an factor the and generation optimally tolerogenic environment. In this review, we focus on interferon (IFN) production within thymus its...
Heterologous immunity is recognized as a significant barrier to transplant tolerance. Whereas it has been established that pathogen-elicited memory T cells can have high or low affinity for cross-reactive allogeneic peptide-MHC, the role of TCR during heterologous not explored. We model with which investigate impact TCR-priming on cell populations following graft rechallenge. In contrast high-affinity priming, low-affinity priming elicited fully differentiated CD45RB(hi) status. High CD45RB...
SHP1 is a tyrosine phosphatase critical to proximal regulation of TCR signaling. Here, analysis CD4-Cre SHP1(fl/fl) conditional knockout thymocytes using CD53, TCRβ, CD69, CD4, and CD8α expression demonstrates the importance in survival post selection (CD53(+) ), single-positive thymocytes. Using Ca(2+) flux assess intensity signaling demonstrated that dampens signal strength these same mature, postselection Consistent with its dampening effect, was also probed functionally peptides can...
Interleukin-15 (IL-15) is often considered a central regulator of memory CD8+ T cells, based primarily on studies recirculating subsets. However, recent work identified IL-15-independent cell populations, including tissue-resident cells (TRM) in some nonlymphoid tissues (NLTs). Whether this reflects the existence IL-15-insensitive unclear. We report that IL-15 complexes (IL-15c) stimulate rapid proliferation and expansion both circulating subsets across lymphoid with varying magnitude by...
Abstract Expression of programmed death 1 (PD-1) on CD8 T cells promotes cell exhaustion during chronic Ag exposure. During acute infections, PD-1 is transiently expressed and has the potential to modulate memory formation. Conserved region C (CR-C), a promoter proximal cis-regulatory element that critical expression in vitro, responds NFATc1, FoxO1, and/or NF-κB signaling pathways. Here, CR-C knockout mouse was established determine its role corresponding effects function vivo. Deletion...
Abstract TCR affinity for peptide MHC dictates the functional efficiency of T cells and their propensity to differentiate into effectors form memory. However, in context chronic infections, it is unclear what overall profile Ag if differs from acute infections. Using comprehensive analysis provided by two-dimensional micropipette adhesion frequency assay common indirect evaluation methods class II tetramer avidity, we tracked IAb GP61–80–specific mouse model (Armstrong) (clone 13)...
Quantification and detection of the t(9;22) (BCR-ABL1) translocation in chronic myelogenous leukemia B-lymphoblastic are important for directing treatment protocols monitoring disease relapse. However, quantification using traditional reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) is dependent on a calibration curve prone to laboratory-to-laboratory variation. Droplet digital (ddPCR) novel method that allows highly sensitive absolute transcript copy number. As such,...
Indications for apheresis procedures are expanding; however, the evidence many is low quality. A better understanding of patterns in United States needed to plan prospective research studies.