A5082110090- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- HIV Research and Treatment
- Mosquito-borne diseases and control
- CAR-T cell therapy research
- SARS-CoV-2 and COVID-19 Research
- Cytokine Signaling Pathways and Interactions
- Immune responses and vaccinations
- Protein Kinase Regulation and GTPase Signaling
- Estrogen and related hormone effects
- COVID-19 Clinical Research Studies
- Diabetes and associated disorders
- Plant and Fungal Interactions Research
- Receptor Mechanisms and Signaling
- Musculoskeletal pain and rehabilitation
- Immune Response and Inflammation
- Probiotics and Fermented Foods
- Cytomegalovirus and herpesvirus research
- Infrared Thermography in Medicine
- Viral Infections and Outbreaks Research
- Urticaria and Related Conditions
- PI3K/AKT/mTOR signaling in cancer
- Glycosylation and Glycoproteins Research
University of Pennsylvania
2016-2024
Philadelphia VA Medical Center
2018-2024
California University of Pennsylvania
2020-2023
Stanford University
2013-2020
Howard Hughes Medical Institute
2013
Vanderbilt University
2013
Center for Rheumatology
2012
Stanford Medicine
2008
New York University
2001-2003
Massachusetts Institute of Technology
2003
Human leukocyte antigen (HLA) genes are the most polymorphic in human genome. They play a pivotal role immune response and have been implicated numerous pathologies, especially autoimmunity infectious diseases. Despite their importance, however, they rarely characterized comprehensively because of prohibitive cost standard technologies technical challenges accurately discriminating between these highly related many allelles. Here we demonstrate high-resolution, cost-effective methodology to...
T follicular helper (Tfh) CD4 cells are crucial providers of B cell help during adaptive immune responses. A circulating population cells, termed cTfh, have similarity to lymphoid Tfh, can provide help, and responded influenza vaccination. However, it is unclear whether human vaccination-induced cTfh respond in an antigen-specific manner they form long-lasting memory. Here, we identified a that expressed multiple activation markers could be readily by coexpression ICOS CD38. This subset more...
Current paradigms of CD8 + T cell–mediated protection in HIV infection center almost exclusively on studies peripheral blood, which is thought to provide a window into immune activity at the predominant sites viral replication lymphoid tissues (LTs). Through extensive comparison thoracic duct lymph (TDL), and LTs different species, we show that many LT memory cells bear phenotypic, transcriptional, epigenetic signatures resident (T RMs ). Unlike their circulating counterparts blood or TDL,...
Significance The recognition of foreign peptide-MHCs by T cells is a central event in adaptive immunity that triggers antigen-specific immune responses against infections and cancer. To study cells, we devised peptide-MHC dodecamer can sensitively detect specifically stain these especially low-affinity rare ones. This technology superior to most current multimers, compatible with existing reagents, inexpensive make, easy use. It has been successfully applied studies human murine αβ γδ flow...
The baseline composition of T cells directly affects later response to pathogens, but the complexity precursor states remains poorly defined. Here, we examined state severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific in unexposed individuals. SARS-CoV-2-specific CD4+ were identified prepandemic blood samples by major histocompatibility complex (MHC) class II tetramer staining and enrichment. Our data revealed a substantial number that expressed memory phenotype markers....
The estrogen receptor α (ER) is a ligand-dependent transcription factor that plays critical role in the development and progression of breast cancer, part, by regulating target genes involved cellular proliferation. To identify novel components affect ER transcriptional response, we performed genetic screen yeast identified RDI1, Rho guanine nucleotide dissociation inhibitor (Rho GDI), as positive regulator transactivation. Overexpression human homologue GDIα, increases ERα, ERβ, androgen...
The T-cell receptor (TCR) is required for maturation and function of regulatory T cells (Tregs), but the ligand specificities Tregs outside context transgenic TCRs are largely unknown. Using peptide-MHC tetramers, we isolated rare specific Foxp3+ directly ex vivo from adult peripheral blood defined their frequency phenotype. We find that a proportion circulating recognize foreign antigens these similar to self-reactive in absence cognate infection. In contrast, frequencies some common...
Follicular helper CD4+ T cells (TFH) play an integral role in promoting B cell differentiation and affinity maturation. Whereas TFH frequencies are increased lymph nodes (LNs) from individuals infected with HIV, humoral immunity remains impaired during chronic HIV infection. Whether inhibits responses LNs unclear. Advances this area have been limited by the difficulty of accessing human lymphoid tissues. Here, we combined high-dimensional mass cytometry receptor repertoire sequencing to...
CXCR5 is a key marker of follicular helper T (TFH) cells. Using primary lymph nodes (LNs) from HIV-infected patients, we identified population CXCR5− CD4+ cells with TFH-cell-like features. This subset becomes expanded in severe HIV infection and characterized by the upregulation activation markers high PD-1 ICOS surface expression. Integrated analyses on phenotypic heterogeneity, functional capacity, cell receptor (TCR) repertoire, transcriptional profile, epigenetic state CXCR5−PD-1+ICOS+...
p23 is an Hsp90-associated protein that regulates signal transduction by the estrogen receptor α (ER); however, mechanism through which governs ER function remains enigmatic. To obtain a collection of molecules with distinct effects on signaling, we screened in yeast series random mutations as well specific sequence alterations based crystal structure and further analyzed these for their effect p23-Hsp90 association <i>in vitro</i> vivo</i>. We found ability mutants to decrease or increase...
Estrogen receptor alpha (ER) coordinates gene expression with cellular physiology in part by controlling receptor- cofactor interactions response to extracellular signals. We have previously shown that the Rho signaling pathway modulates ER transcriptional activation. now demonstrate GDI-dependent increase transactivation is dependent on AF-2 coactivator binding site, prompting us examine regulation of coactivators GDI. Indeed, GDI cooperates GRIP1 ligand-independent and ligand-dependent...
Bacterial oligopeptide permeases are members of the large family ATP binding cassette transporters and typically import peptides 3 to 5 amino acids, apparently independently sequence. Oligopeptide needed for bacteria utilize as nutrient sources sometimes involved in signal transduction pathways. The Bacillus subtilis permease stimulates competence development initiation sporulation, at least part, by importing specific signaling peptides. We isolated rare, partly functional mutations B. opp....
Memory T cells are conventionally associated with durable recall responses. In our longitudinal analyses of CD4+ cell responses to the yellow fever virus (YFV) vaccine by peptide-MHC tetramers, we unexpectedly found CD45RO-CCR7+ virus-specific that expanded shortly after vaccination and persisted months years immunization. Further phenotypic revealed presence stem cell-like memory within this subset. addition, lacking known markers functionally resembling genuine naive were identified,...
Abstract The baseline composition of T cells directly impacts later response to a pathogen, but the complexity precursor states remains poorly defined. Here we examined state SARS-CoV-2 specific in unexposed individuals. CD4 + were identified pre-pandemic blood samples by class II peptide-MHC tetramer staining and enrichment. Our data revealed substantial number that expressed memory phenotype markers, including with gut homing receptors. cell clones generated from tetramer-labeled...
Abstract The antiviral response to influenza virus is complex and multifaceted, involving many immune cell subsets. There an urgent need understand the role of CD4+ T cells, which orchestrate effective response, improve vaccine design strategies. In this study, we analyzed PBMCs from human participants immunized with vaccine, using high-dimensional single-cell proteomic profiling by mass cytometry. Data were a novel clustering algorithm, denoised ragged pruning, define possible...
How baseline T cell characteristics impact human responses to novel pathogens remains unknown. Here, we address this question by studying the CD4+ response in unexposed individuals live attenuated yellow fever virus (YFV) vaccine. We quantified virus-specific population dynamics over time using class II peptide-MHC tetramers. Our data revealed that, even absence of known viral exposure, memory phenotype cells were found majority precursors healthy adults. Pre-existing can be divided into two...
Factors that contribute to durable immunological memory remain incompletely understood. In our longitudinal analyses of CD4
Abstract CD4 + T cell senescence has been linked to repeated antigen stimulation. However, how different types of chronic antigenic exposures impact differentiation and function remains incompletely understood. Using rheumatoid arthritis (RA) cytomegalovirus (CMV) as models for persistent stimulation in autoimmunity viral infection, we performed high-dimensional mass cytometry analyses examine their effects on differentiation. We found that CMV seropositive adults have a significant...
Follicular-helper T cells (T FH ) are an essential arm of the adaptive immune system. Although were first discovered through their ability to contribute antibody affinity maturation co-stimulatory interactions with B cells, new light has been shed on remain a complex and functionally plastic cell type. Due lack sample availability, however, many studies have limited characterizing in mice or non-canonical tissue types, such as peripheral blood. Such constraints resulted limited, sometimes...