A5102905062- HIV Research and Treatment
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- HIV/AIDS Research and Interventions
- HIV-related health complications and treatments
- Reproductive System and Pregnancy
- Cancer Genomics and Diagnostics
- Proteoglycans and glycosaminoglycans research
- Single-cell and spatial transcriptomics
- Plant Gene Expression Analysis
- Long-Term Effects of COVID-19
- Respiratory viral infections research
- HIV/AIDS drug development and treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- Gynecological conditions and treatments
- Immune Response and Inflammation
- Extracellular vesicles in disease
- Endometriosis Research and Treatment
- Glycosylation and Glycoproteins Research
- Tryptophan and brain disorders
- Plant Molecular Biology Research
Gladstone Institutes
2019-2024
University of California, San Francisco
2019-2024
Anhui Agricultural University
2024
Institute of Virology of the Slovak Academy of Sciences
2021
Convalescing coronavirus disease 2019 (COVID-19) patients mount robust T cell responses against SARS-CoV-2, suggesting an important role of cells in viral clearance. To date, the phenotypes SARS-CoV-2-specific remain poorly defined. Using 38-parameter CyTOF, we phenotyped longitudinal specimens CD4+ and CD8+ from nine individuals who recovered mild COVID-19. were exclusively Th1 predominantly Tcm with phenotypic features helper function. Temra a state less terminal differentiation than most...
While mRNA vaccines are proving highly efficacious against SARS-CoV-2, it is important to determine how booster doses and prior infection influence the immune defense they elicit, whether protect variants. Focusing on T cell response, we conducted a longitudinal study of infection-naïve COVID-19 convalescent donors before vaccination after their first second vaccine doses, using high-parameter CyTOF analysis phenotype SARS-CoV-2-specific cells. Vaccine-elicited spike-specific cells responded...
The latent reservoir is a major barrier to HIV cure. As latently infected cells cannot be phenotyped directly, the features of in vivo have remained elusive. Here, we describe method that leverages high-dimensional phenotyping using CyTOF trace reactivated ex their original pre-activation states. Our results suggest that, contrary common assumptions, not randomly distributed among cell subsets, and remarkably conserved between individuals. However, composition differs tissues blood, as do...
Abstract Despite the success of combination antiretroviral therapy (ART) for individuals living with HIV, mild forms HIV-associated neurocognitive disorder (HAND) continue to occur. Brain microglia form principal target HIV infection in brain. It remains unknown how these cells leads neuroinflammation, neuronal dysfunction, and/or death observed HAND. Utilizing two different inducible pluripotent stem cell-derived brain organoid models (cerebral and choroid plexus [ChP] organoids) containing...
The primary reservoir for HIV is within memory CD4+ T cells residing tissues, yet the features that make some of these more susceptible than others to infection by not well understood. Recent studies demonstrated CCR5-tropic HIV-1 efficiently enters tissue-derived expressing CD127, alpha chain IL7 receptor, but rarely completes replication cycle. We now demonstrate inability replicate in CD127-expressing due post-entry restriction SAMHD1. Rather, relative other cell subsets, are highly prone...
High-parameter single-cell phenotyping has enabled in-depth classification and interrogation of immune cells, but to date not allowed for glycan characterization. Here, we develop CyTOF-Lec as an approach simultaneously characterize many protein features human cells at the level. We implemented compare between different subsets from blood multiple tissue compartments, HIV-infected cell cultures. Using bioinformatics approaches distinguish preferential infection cellular viral-induced...
ABSTRACT Pre-existing anti-interferon alpha (anti-IFN-α) autoantibodies in blood are associated with susceptibility to life-threatening COVID-19. However, it is unclear whether anti-IFN-α the airways – initial site of infection can also determine disease outcomes. In this study, we developed a new multiparameter technology, flowBEAT, quantify and profile isotypes anti-SARS-CoV-2 antibodies longitudinal samples collected over 20 months from airway matching 129 donors mild, moderate, severe We...
Do seminal plasma (SP) and its constituents affect the decidualization capacity transcriptome of human primary endometrial stromal fibroblasts (eSFs)?SP promotes eSFs from women with without inflammatory disorders (polycystic ovary syndrome (PCOS), endometriosis) in a manner that is not mediated through semen amyloids associated potent transcriptional response, including induction interleukin (IL)-11, cytokine important for SP-induced decidualization.Clinical studies have suggested SP can...
Convalescing COVID-19 patients mount robust T cell responses against SARS-CoV-2, suggesting an important role for cells in viral clearance. To date, the phenotypes of SARS-CoV-2-specific remain poorly defined. Using 38-parameter CyTOF, we phenotyped longitudinal specimens CD4+ and CD8+ from nine individuals who recovered mild COVID-19. were exclusively Th1 cells, predominantly Tcm with phenotypic features helper function. Temra a state less terminal differentiation than most cells. Subsets...
Relatively little is known about features of T cells targeted by HIV in vivo. By applying bioinformatics analysis to mass cytometry (CyTOF)-phenotyped specimens from individuals with viremia and in-vitro-infected uninfected donors, we provide an atlas the phenotypes vivo vitro HIV-susceptible cells. helper 17 (Th17) α4β1+ are preferentially vivo, whereas effector memory (Tem), transitional (Ttm), Th1, Th1/Th17 subsets vitro. Multiple proteins—including chemokine cytokine receptors—are...
While mRNA vaccines are proving highly efficacious against SARS-CoV-2, it is important to determine how booster doses and prior infection influence the immune defense they elicit, whether protect variants. Focusing on T cell response, we conducted a longitudinal study of infection-naïve COVID-19 convalescent donors before vaccination after their first second vaccine doses, using high-parameter CyTOF analysis phenotype SARS-CoV-2-specific cells. Vaccine-elicited spike-specific cells responded...
Abstract Introduction Sex‐specific differences affect multiple aspects of HIV infection, yet few studies have quantified levels in tissues from women. Since an functional cure will likely require a major reduction infected cells most tissues, we measured total and intact DNA the transcription profile blood, gut, genital tract liver HIV‐positive antiretroviral therapy (ART) ‐treated Methods Peripheral blood mononuclear (PBMC) biopsies gastrointestinal (ileum, colon, rectosigmoid +/‐ liver)...
Abstract CD8+ T cells can potentiate long-lived immunity against COVID-19. We screened longitudinally-sampled convalescent human donors SARS-CoV-2 tetramers and identified a participant with an immunodominant response residues 322 to 311 of nucleocapsid (Nuc322–331), peptide conserved in all variants concern reported date. conducted 38-parameter cytometry by time flight on tetramer-identified Nuc322–331–specific CD4+ recognizing the entire spike proteins, took 32 serological measurements....
Abstract Background Single-cell RNA sequencing (scRNA-seq) provides high-dimensional measurements of transcript counts in individual cells. However, high assay costs and artifacts associated with analyzing samples across multiple runs limit the study large numbers samples. Sample multiplexing technologies such as MULTI-seq antibody hashing using single-cell kit (SCMK) reagents (BD Biosciences) use sample-specific sequence tags to enable be sequenced a pooled format, markedly lowering...
Abstract The biosynthesis and accumulation of secondary metabolites play a vital role in determining the quality medicinal plants, with carbohydrate metabolism often influencing metabolism. To understand potential regulatory mechanism, exogenous sugars (sucrose, glucose/fructose) were applied to leaves Cyclocarya paliurus , highly valued multiple function tree species. results showed that enhanced soluble sugar starch while increasing enzyme activity related In addition, plant height was...
Preexisting anti–interferon-α (anti–IFN-α) autoantibodies in blood are associated with susceptibility to life-threatening COVID-19. However, it is unclear whether anti–IFN-α the airways, initial site of infection, can also determine disease outcomes. In this study, we developed a multiparameter technology, FlowBEAT, quantify and profile isotypes anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies longitudinal samples collected over 20 months from airways 129 donors...
The majority of HIV infections are established through the genital or rectal mucosa. Fibroblasts abundant in these tissues, and although not susceptible to infection, can potently enhance infection CD4+ T cells. Hyaluronic acid (HA) is a major component extracellular matrix fibroblasts, its levels influenced by inflammatory state tissue. Since inflammation known facilitate sexual transmission, we investigated role HA mucosal fibroblast-mediated enhancement infection. Depletion CRISPR-Cas9...
Latent HIV infection is the main barrier to cure, and most HIV-infected cells reside in gut, where distinct but unknown mechanisms may promote viral latency. Transforming growth factor β (TGF-β), which induces expression of CD103 on tissue-resident memory T cells, has been implicated Using as a surrogate marker identify that have undergone TGF-β signaling, we compared RNA/DNA contents cellular transcriptomes
CD8+ T cells are important antiviral effectors that can potentiate long-lived immunity against COVID-19, but a detailed characterization of these has been hampered by technical challenges. We screened 21 well-characterized, longitudinally-sampled convalescent donors recovered from mild COVID-19 collection SARS-CoV-2 tetramers, and identified one participant with an immunodominant response Nuc322-331, peptide is conserved in all the variants-of-concern reported to date. conducted 38-parameter...
T cells residing in mucosal tissues play important roles homeostasis and defense against microbial pathogens. The gut female reproductive tract (FRT) are both tolerogenic environments, but they differ the kinds of foreign Ags need to tolerate. How these different environments influence properties their is poorly understood, for understanding women's health. We recruited antiretroviral therapy-suppressed women living with HIV who donated, within one visit, blood tissue samples from ileum,...