A5040945502- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- SARS-CoV-2 and COVID-19 Research
- Systemic Lupus Erythematosus Research
- Immune responses and vaccinations
- Atherosclerosis and Cardiovascular Diseases
- Lymphoma Diagnosis and Treatment
- Dermatology and Skin Diseases
- COVID-19 Clinical Research Studies
- Single-cell and spatial transcriptomics
- Long-Term Effects of COVID-19
- Advanced Biosensing Techniques and Applications
- Cutaneous lymphoproliferative disorders research
- Bacteriophages and microbial interactions
- Vaccine Coverage and Hesitancy
- Monoclonal and Polyclonal Antibodies Research
- CAR-T cell therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- HIV Research and Treatment
- Autoimmune Bullous Skin Diseases
- Systemic Sclerosis and Related Diseases
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- IL-33, ST2, and ILC Pathways
- Multiple Sclerosis Research Studies
Benaroya Research Institute
2018-2024
Virginia Mason Medical Center
2022-2023
National Institutes of Health
2014-2019
National Institute of Allergy and Infectious Diseases
2017-2019
Children's Hospital of Philadelphia
2012-2014
University of Pennsylvania
2012-2014
Human blood and lymph contain circulating CD4 + CD103 cutaneous resident memory T cells that can seed distant skin sites. See the related Focus by Carbone Gebhardt .
Integrating form and function for design Antibodies are broadly used in therapies as research tools because they can be generated against a wide range of targets. Efficacy often increased by clustering antibodies multivalent assemblies. Divine et al. designed antibody nanocages from two components: One is an antibody-binding homo-oligomic protein the other itself. Computationally proteins drive assembly architectures, allowing control symmetry valency. The display enhances antibody-dependent...
Foxp3 is a transcription factor required for the development of regulatory T cells (Treg). Mice and humans with loss function suffer from uncontrolled autoimmunity inflammatory disease. Expression necessary anti-inflammatory capacity Treg, but whether activity further subject to regulation by extracellular signals unclear. The primary structure contains four cyclin-dependent kinase (CDK) motifs (Ser/Thr-Pro) within N-terminal repressor domain, we show that CDK2 can partner cyclin E...
Summary The recently emerged SARS-CoV-2 virus is currently causing a global pandemic and cases continue to rise. majority of infected individuals experience mildly symptomatic coronavirus disease 2019 (COVID-19), but it unknown whether this can induce persistent immune memory that might contribute herd immunity. Thus, we performed longitudinal assessment recovered from COVID-19 determine if they develop sustain immunological against the virus. We found developed SARS-CoV-2-specific IgG...
Modern immunologic research increasingly requires high-dimensional analyses to understand the complex milieu of cell types that comprise tissue microenvironments disease. To achieve this, we developed Infinity Flow combining hundreds overlapping flow cytometry panels using machine learning enable simultaneous analysis coexpression patterns surface-expressed proteins across millions individual cells. In this study, demonstrate approach allows comprehensive cellular constituency steady-state...
Abstract The recently emerged SARS-CoV-2 virus is currently causing a global pandemic and cases continue to rise. majority of infected individuals experience mildly symptomatic coronavirus disease 2019 (COVID-19), but it unknown whether this can induce persistent immune memory that might contribute herd immunity. Thus, we performed longitudinal assessment recovered from COVID-19 determine if they develop sustain immunological against the virus. We found developed SARS-CoV-2-specific IgG...
Genome-wide association studies (GWAS) have identified hundreds of genetic signals associated with autoimmune disease. The majority these are located in non-coding regions and likely impact cis -regulatory elements (cRE). Because cRE function is dynamic across cell types states, profiling the epigenetic status physiological processes necessary to characterize molecular mechanisms by which variants contribute disease risk. We localized risk from 15 GWAS active during TCR-CD28 co-stimulation...
Abstract Severe lupus often includes psychiatric and neurological sequelae, although the cellular contributors to CNS disease remain poorly defined. Using intravascular staining discriminate tissue-localized from blood-borne cells, we find substantial accumulation of CD8 + T cells relative other lymphocytes in brain tissue, which correlates with limited neuropathology. This is contrast all affected organs, where infiltrating CD4 are predominant. Brain-infiltrating represent an activated...
Abstract Antibodies are widely used in biology and medicine, there has been considerable interest multivalent antibody formats to increase binding avidity enhance signaling pathway agonism. However, currently no general approaches for forming precisely oriented assemblies with controlled valency. We describe the computational design of two-component nanocages that overcome this limitation by uniting form function. One structural component is any or Fc fusion second a designed Fc-binding...
Multiple sclerosis (MS) is a demyelinating inflammatory disease of the CNS treated by diverse disease-modifying therapies that suppress immune system. Severe acute respiratory syndrome coronavirus 2 mRNA vaccines have been very effective in immunocompetent individuals, but whether MS patients with modifying are afforded same protection not known. This study determined dimethyl fumarate caused momentary reduction anti-Spike (S)-specific Abs and CD8 T cell response. B cell-depleting...
Abstract Chemically defined serum-free media are increasingly used as a tool to help standardize experiments by eliminating the potential variability contributed pooled serum. These formulated for culture and expansion of specific cell types, maintaining viability without need exogenous animal proteins. Formulated could thus improve reduce during sample preparation flow cytometry, yet thorough analysis how such impact fluorochrome–Ab conjugates has not been performed. In this study, we...
Summary Immune memory is tailored by cues that lymphocytes perceive during priming. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic created a situation in which nascent could be tracked through additional antigen exposures. Both SARS-CoV-2 infection and vaccination induce multifaceted, functional immune memory, but together they engender improved protection from disease, termed “hybrid immunity”. We therefore investigated how vaccine-induced shaped previous...
Abstract Tissue-resident memory T cells (T RM ) persist locally in non-lymphoid tissues where they provide front-line defense against recurring insults. at barrier surfaces express the markers CD103 and/or CD69 which function to retain them epithelial tissues. In humans, neither long-term migratory behavior of nor their ability re-enter circulation and potentially migrate distant tissue sites have been investigated. Using explant cultures, we found that CD4 + human skin can downregulate exit...
ABSTRACT Genome-wide association studies (GWAS) have identified hundreds of genetic signals associated with autoimmune disease. The majority these are located in non-coding regions and likely impact cis -regulatory elements (cRE). Because cRE function is dynamic across cell types states, profiling the epigenetic status physiological processes necessary to characterize molecular mechanisms by which variants contribute disease risk. We localized risk from 15 GWAS active during TCR-CD28...
Genome-wide association studies (GWAS) have identified hundreds of genetic signals associated with autoimmune disease. The majority these are located in non-coding regions and likely impact cis -regulatory elements (cRE). Because cRE function is dynamic across cell types states, profiling the epigenetic status physiological processes necessary to characterize molecular mechanisms by which variants contribute disease risk. We localized risk from 15 GWAS active during TCR-CD28 costimulation...
Abstract T cells and structural coordinate appropriate inflammatory responses restoration of barrier integrity following insult. Dysfunctional cell activity precipitates tissue pathology that occurs alongside disease-associated alterations subsets, but the mechanisms by which promote these changes remain unclear. We show subsets circulating skin-resident CD4 + distinct transcriptional outcomes in human keratinocytes dermal fibroblasts correspond with divergent cytokine production. Using...
Genome-wide association studies (GWAS) have identified hundreds of genetic signals associated with autoimmune disease. The majority these are located in non-coding regions and likely impact cis -regulatory elements (cRE). Because cRE function is dynamic across cell types states, profiling the epigenetic status physiological processes necessary to characterize molecular mechanisms by which variants contribute disease risk. We localized risk from 15 GWAS active during TCR-CD28 costimulation...