A5077937026- Single-cell and spatial transcriptomics
- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Cancer Genomics and Diagnostics
- Immunotherapy and Immune Responses
- Mosquito-borne diseases and control
- Lymphoma Diagnosis and Treatment
- Cell Image Analysis Techniques
- Immune cells in cancer
- Cutaneous lymphoproliferative disorders research
- Viral Infections and Vectors
- Allergic Rhinitis and Sensitization
- Asthma and respiratory diseases
- Acute Myeloid Leukemia Research
- HIV Research and Treatment
- Cancer Cells and Metastasis
- Fungal Infections and Studies
- Breast Cancer Treatment Studies
- Gene expression and cancer classification
- Chemokine receptors and signaling
- Advanced Fluorescence Microscopy Techniques
- Hematopoietic Stem Cell Transplantation
- Artificial Immune Systems Applications
- Advanced Biosensing Techniques and Applications
- CAR-T cell therapy research
Fred Hutch Cancer Center
2022-2025
Stanford University
2019-2024
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa
2023-2024
Seattle University
2023
Murdoch Children's Research Institute
2019
Ductal carcinoma in situ (DCIS) is a pre-invasive lesion that thought to be precursor invasive breast cancer (IBC). To understand the changes tumor microenvironment (TME) accompanying transition IBC, we used multiplexed ion beam imaging by time of flight (MIBI-TOF) and 37-plex antibody staining panel interrogate 79 clinically annotated surgical resections using machine learning tools for cell segmentation, pixel-based clustering, object morphometrics. Comparison normal with patient-matched...
B cells are capable of a wide range effector functions including antibody secretion, antigen presentation, cytokine production, and generation immunological memory. A consistent strategy for classifying human by using surface molecules is essential to harness this functional diversity clinical translation. We developed highly multiplexed screen quantify the co-expression 351 on millions cells. identified differentially expressed aligned their variance with isotype usage, VDJ sequence,...
Allergen-specific immunoglobulin E (IgE) antibodies mediate pathology in diseases such as allergic rhinitis and food allergy. Memory B cells (MBCs) contribute to circulating IgE by regenerating IgE-producing plasma upon allergen encounter. Here, we report a population of type 2–polarized MBCs defined CD23 hi , IL-4Rα CD32 low at both the transcriptional surface protein levels. These MBC2s are enriched IgG1- IgG4-expressing while constitutively expressing germline transcripts for IgE. from...
Regulatory B cells (Bregs) suppress immune responses through the secretion of interleukin-10 (IL-10). This immunomodulatory capacity holds therapeutic potential, yet a definitional immunophenotype for enumeration and prospective isolation capable IL-10 production remains elusive. Here, we simultaneously quantify cytokine in human peripheral across range stimulatory conditions time points using mass cytometry. Our analysis shows that multiple functional cell subsets produce no phenotype...
Single-cell spatial transcriptomics promises a highly detailed view of cell's transcriptional state and microenvironment, yet inaccurate cell segmentation can render this data murky by misattributing large numbers transcripts to nearby cells or conjuring nonexistent cells. We adopt methods from ab initio simulation rapidly infer morphologically plausible boundaries that preserve type heterogeneity. Benchmarking applied datasets generated three commercial platforms show superior performance...
Abstract Allergen-specific IgE antibodies mediate allergic pathology in diseases such as rhinitis and food allergy. Memory B cells (MBCs) contribute to circulating by regenerating IgE-producing plasma upon allergen encounter. We report a population of type 2 polarized MBCs defined CD23 hi , IL-4Rα CD32 low at the transcriptional surface protein levels. These “MBC2s” are enriched IgG1 IgG4-expressing cells, while constitutively expressing germline transcripts for IgE. from patients with...
Single-cell technologies generate large, high-dimensional datasets encompassing a diversity of omics. Dimensionality reduction captures the structure and heterogeneity original dataset, creating low-dimensional visualizations that contribute to human understanding data. Existing algorithms are typically unsupervised, using measured features manifolds, disregarding known biological labels such as cell type or experimental time point. We repurpose classification algorithm, linear discriminant...
Approximately 5 million dengue virus-infected patients progress to a potentially life-threatening severe (SD) infection annually. To identify the immune features and temporal dynamics underlying SD progression, we performed deep profiling by mass cytometry of PBMCs collected longitudinally from progressors (SDp) uncomplicated (D) patients. While D is characterized early activation innate responses, in SDp there rapid expansion IgG-secreting plasma cells memory regulatory T cells....
Persons with HIV (PWH) on long-term antiretroviral therapy (ART) have a higher incidence and prevalence of cardiometabolic diseases attributed, in part, to persistent inflammation despite viral suppression. In addition traditional risk factors, immune responses co-infections such as cytomegalovirus (CMV) may play an unappreciated role comorbidities offer new potential therapeutic targets subgroup individuals. We assessed the relationship CX3CR1 + , GPR56 CD57 +/- T cells (termed CGC )...
Cutaneous T cell lymphomas (CTCLs) are skin cancers with poor survival rates and limited treatments. While immunotherapies have shown some efficacy, the immunological consequences of administering immune-activating agents to CTCL patients not been systematically characterized. We apply a suite high-dimensional technologies investigate local, cellular, systemic responses in receiving either mono- or combination anti-PD-1 plus interferon-gamma (IFN-γ) therapy. Neoplastic cells display no...
Abstract Ductal carcinoma in situ (DCIS) is a pre-invasive lesion that thought to be precursor invasive breast cancer (IBC). To understand how the tumor microenvironment (TME) changes with transition IBC, we used Multiplexed Ion Beam Imaging by time of flight (MIBI-TOF) and 37-plex antibody staining panel analyze 140 clinically annotated surgical resections covering full spectrum progression. We compared normal, DCIS, IBC tissues using machine learning tools for multiplexed cell...
Abstract Lymphoid specification in human hematopoietic progenitors is not fully understood. To better associate lymphoid identity with protein-level cell features, we conduct a highly multiplexed single-cell proteomic screen on bone marrow progenitors. This identifies terminal deoxynucleotidyl transferase (TdT), specialized DNA polymerase intrinsic to VDJ recombination, broadly expressed within CD34 + prior B/T emergence. While these TdT cells coincide granulocyte-monocyte progenitor (GMP)...
Summary Cellular metabolism regulates immune cell activation, differentiation and effector functions to the extent that its perturbation can augment responses. However, analytical technologies available study cellular lack single-cell resolution, obscuring metabolic heterogeneity connection phenotype function. To end, we utilized high-dimensional, antibody-based simultaneously quantify regulome in combination with phenotypic identity. Mass cytometry (CyTOF)-based application of this approach...
Hematopoietic stem and progenitor cell (HSPC) transplantation is an essential therapy for hematological conditions, but finer definitions of human HSPC subsets with associated function could enable better tuning grafts more routine, lower-risk application. To deeply phenotype HSPCs, following a screen 328 antigens, we quantified 41 surface proteins functional regulators on millions CD34+ CD34- cells, spanning four primary hematopoietic tissues: bone marrow, mobilized peripheral blood, cord...
Dysregulation of the bone marrow (BM) niche in multiple myeloma (MM) alters composition and state resident immune cells, potentially impeding anti-tumor immunity. One common mechanism inhibition solid tumors is induction exhaustion tumor-specific T cells. However, extent cell tumor recognition not well-characterized MM. As specific mechanisms evasion are critical for devising effective therapeutic strategies, we deeply profiled CD8
Abstract To evaluate the impact of heterogeneous B cells in health and disease, comprehensive profiling is needed at a single cell resolution. We developed highly-multiplexed screen to quantify co-expression 351 surface molecules on low numbers primary cells. identified dozens differentially expressed aligned their variance with isotype usage, metabolism, biosynthesis activity, signaling response. Here, we propose new classification scheme segregate peripheral blood into ten unique subsets,...
Summary Approximately five million dengue virus-infected patients, particularly children, progress to a potentially life-threatening severe (SD) infection annually. To identify the immune features and temporal dynamics underlying SD progression, we performed deep profiling by mass cytometry of PBMCs collected longitudinally from progressors (SDp) uncomplicated (D) patients. While D is characterized early activation innate responses, in SDp there rapid expansion IgG-secreting plasma cells...
Abstract Single-cell technologies generate large, high-dimensional datasets encompassing a diversity of omics. Dimensionality reduction enables visualization data by representing cells in two-dimensional plots that capture the structure and heterogeneity original dataset. Visualizations contribute to human understanding are useful for guiding both quantitative qualitative analysis cellular relationships. Existing algorithms typically unsupervised, utilizing only measured features manifolds,...
Abstract Lymphoid specification in human hematopoietic progenitors is not fully understood. To better associate lymphoid identity with protein-level cell features, we conducted a highly multiplexed single-cell proteomic screen on bone marrow progenitors. This identified terminal deoxynucleotidyl transferase (TdT), specialized DNA polymerase intrinsic to VDJ recombination, broadly expressed within CD34+ prior B/T emergence. While these TdT+ cells coincided granulocyte-monocyte progenitor...
Abstract Regulatory B cells (Bregs) can suppress immune responses through the secretion of IL-10 and other anti-inflammatory cytokines. This immunomodulatory capacity holds therapeutic potential, yet a definitional immunophenotype for enumeration prospective isolation capable production remains elusive. We therefore applied mass cytometry to simultaneously quantify cytokine in human peripheral across range stimulatory conditions timepoints. While multiple cell subsets produced IL-10, no...