A5013397062- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- COVID-19 Clinical Research Studies
- Mycorrhizal Fungi and Plant Interactions
- Diabetes and associated disorders
- CAR-T cell therapy research
- Genomics and Phylogenetic Studies
- Organ Transplantation Techniques and Outcomes
- Respiratory Support and Mechanisms
- Microbial infections and disease research
- NF-κB Signaling Pathways
- Immunodeficiency and Autoimmune Disorders
- Blood Coagulation and Thrombosis Mechanisms
- Cytokine Signaling Pathways and Interactions
- Transplantation: Methods and Outcomes
- Protein Degradation and Inhibitors
- Adipokines, Inflammation, and Metabolic Diseases
- Multiple Myeloma Research and Treatments
- Neurobiology and Insect Physiology Research
- Antibiotics Pharmacokinetics and Efficacy
- Renal Transplantation Outcomes and Treatments
- Antibiotic Resistance in Bacteria
- Chronic Obstructive Pulmonary Disease (COPD) Research
Johns Hopkins Medicine
2021-2024
Johns Hopkins University
2021-2024
University of Miami
2014-2020
Cornell University
2012-2018
Plant (United States)
2015-2018
IL-2R signaling is essential for regulatory T cell (Treg) function. However, the precise contribution of IL-2 during Treg thymic development, peripheral homeostasis and lineage stability remains unclear. Here we show that required by Tregs at an early step expansion survival, a later functional maturation. Using inducible, conditional deletion CD25 in Tregs, also find indispensable homeostasis, whereas largely IL-2-independent. knockout have increased apoptosis, oxidative stress, signs...
SARS-CoV-2 infection is associated with thrombotic and microvascular complications. The cause of coagulopathy in the disease incompletely understood.A single-center cross-sectional study including 66 adult COVID-19 patients (40 moderate, 26 severe disease), 9 controls, performed between 04/2020 10/2020. Markers coagulation, endothelial cell function [angiopoietin-1,-2, P-selectin, von Willebrand Factor Antigen (WF:Ag), Ristocetin Cofactor, ADAMTS13, thrombomodulin, soluble Endothelial...
Many eukaryotes interact with heritable endobacteria to satisfy diverse metabolic needs. Some of these interactions are facultative symbioses, in which one partner is not essential the other. Facultative symbioses expected be transitional stages along an evolutionary trajectory toward obligate relationships. We tested this theory prediction Ca. Glomeribacter gigasporarum, nonessential endosymbionts arbuscular mycorrhizal fungi (Glomeromycota). found that mutualisms can both ancient and...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in coagulation activation although it is usually not associated with consumption coagulopathy. D-dimers are also commonly elevated despite systemic hypofibrinolysis. To understand these unusual features of disease 2019 (COVID-19) coagulopathy, 64 adult patients SARS-CoV-2 (36 moderate and 28 severe) 16 controls were studied. We evaluated the repertoire plasma protease inhibitors (Serpins, Kunitz, Kazal,...
The mycoplasma-related endobacteria (MRE), representing a recently discovered lineage of Mollicutes, are widely distributed across arbuscular mycorrhizal fungi (AMF, Glomeromycota). AMF colonize roots most terrestrial plants and improve plant mineral nutrient uptake in return for plant-assimilated carbon. role MRE the biology their fungal hosts is unknown. To start characterizing this association, we assessed partitioning genetic diversity within individuals phylogeographic range. We further...
Abstract Resting central Tregs (cTregs) and activated effector (eTregs) are required for self-tolerance, but the heterogeneity relationships within between phenotypically distinct subsets of cTregs eTregs poorly understood. By extensive immune profiling deep sequencing TCR-β V regions, two cTregs, based on expression Ly-6C, three eTregs, distinctive CD62L, CD69, CD103, were identified. Ly-6C+ exhibited lower basal activation, expressed average affinity TCRs, less efficiently developed into...
Genetically predisposed CTLA4 insufficiency in humans is associated with gastric cancer development, which paradoxical to the prototypical role of suppressing antitumor immunity. a critical immune checkpoint against autoimmune disorders. Autoimmunity has been implicated protumor or activities. Here, we show that initiates de novo tumorigenesis mouse stomach through inflammation triggered by host-intrinsic dysregulation rather than microbiota, age-associated progression malignancy accompanied...
The cytokine interleukin-2 (IL-2) is critical for the functions of regulatory T cells (Tregs). contribution polymorphisms in gene encoding IL-2 receptor α subunit (IL2RA), which are associated with type 1 diabetes, difficult to determine because autoimmunity depends on variations multiple genes, where any one product small. We investigated mechanisms whereby a modest reduction IL-2R signaling selectively lymphocytes influenced development diabetes NOD mouse model. sensitivity was reduced by...
With improvements in medical management and surgical technique the field of solid organ transplantation, many historically prominent causes liver allograft injury have been ameliorated or, case Hepatitis C virus, eliminated altogether. In this transformed clinical landscape, antibody-mediated rejection (AMR) has emerged as a defining barrier to maintenance long-term function. The liver's unique anatomy, high regenerative capacity, tolerogenic immunological environment tend mitigate severest...
The New Delhi metallo-β-lactamase (NDM) is a mediator of broad antimicrobial resistance among the Enterobacteriaceae and other gram-negative pathogens that cause opportunistic nosocomial infections. In decade since its discovery, NDM has spread worldwide represents an increasing threat to public health. capable hydrolyzing nearly all known β-lactam antibiotics, including carbapenems, due zinc ion-dependent catalytic mechanism unaffected by available β-lactamase inhibitors. We report case...
Abstract IL-2R signaling is essential for thymic development and homeostasis of CD4+Foxp3+ Tregs, which are required to maintain self-tolerance. Although deletion IL-2/IL-2R in mice leads lethal autoimmunity, disease delayed comparison lacking Foxp3. It unclear whether this delay due redundant Tregs by other γc cytokines, or loss IL-2 activation autoreactive T cells. To explore function we evaluated the consequence germline knockout (gKO) versus Treg-conditional (cKO) CD25. Both types KO...
Abstract Low frequency of tumor-specific T cells represents one major reason for failed immunotherapy. IL-2 can boost tumor-reactive but its benefit is limited due to toxicity and potential off-target effects. We developed a novel IL-2/CD25 fusion protein which exhibits more favorable pharmacology when compared IL-2. At low doses, targets the high affinity IL-2R selectively boosts Tregs. Here we show that single administration dose mouse in conjunction with cognate peptide LPS amplified...