Alexandra‐Chloé Villani
- Cancer Immunotherapy and Biomarkers
- Single-cell and spatial transcriptomics
- Immune Cell Function and Interaction
- Immune cells in cancer
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- COVID-19 Clinical Research Studies
- IL-33, ST2, and ILC Pathways
- Immunotherapy and Immune Responses
- SARS-CoV-2 and COVID-19 Research
- Inflammatory Bowel Disease
- Asthma and respiratory diseases
- Extracellular vesicles in disease
- Microscopic Colitis
- Cell Image Analysis Techniques
- interferon and immune responses
- Reproductive System and Pregnancy
- Diabetes and associated disorders
- Immune responses and vaccinations
- Viral Infections and Immunology Research
- vaccines and immunoinformatics approaches
- Gastrointestinal motility and disorders
- Cancer Genomics and Diagnostics
- Long-Term Effects of COVID-19
- COVID-19 Impact on Reproduction
Broad Institute
2016-2025
Massachusetts General Hospital
2016-2025
Harvard University
2014-2025
Center for Cancer Research
2017-2025
Massachusetts Institute of Technology
2014-2025
Boston University
2023
MGH Institute of Health Professions
2021-2022
Global Cancer Institute
2021
Harvard University Press
2020
Montreal General Hospital
2008-2010
To explore the distinct genotypic and phenotypic states of melanoma tumors, we applied single-cell RNA sequencing (RNA-seq) to 4645 single cells isolated from 19 patients, profiling malignant, immune, stromal, endothelial cells. Malignant within same tumor displayed transcriptional heterogeneity associated with cell cycle, spatial context, a drug-resistance program. In particular, all tumors harbored malignant two states, such that characterized by high levels MITF transcription factor also...
What's in a drop of blood? Blood contains many types cells, including immune system components. Immune cells used to be characterized by marker-based assays, but now classification relies on the genes that express. Villani et al. deep sequencing at single-cell level and unbiased clustering define six dendritic cell four monocyte populations. This refined analysis has identified, among others, previously unknown population potently activates T cells. Further culture revealed possible...
Abstract X chromosome inactivation (XCI) silences transcription from one of the two chromosomes in female mammalian cells to balance expression dosage between XX females and XY males. XCI is, however, incomplete humans: up one-third X-chromosomal genes are expressed both active inactive (Xa Xi, respectively) cells, with degree ‘escape’ varying individuals 1,2 . The extent which is shared tissues remains poorly characterized 3,4 , as does manifests detectable sex differences gene 5 phenotypic...
Understanding humoral responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical for improving diagnostics, therapeutics, and vaccines. Deep serological profiling of 232 disease 2019 (COVID-19) patients 190 pre–COVID-19 era controls using VirScan revealed more than 800 epitopes in the SARS-CoV-2 proteome, including 10 likely recognized by neutralizing antibodies. Preexisting antibodies ORF1, whereas only COVID-19 patient primarily spike protein nucleoprotein. A...
Immune Variation It is difficult to determine the mechanistic consequences of context-dependent genetic variants, some which may be related disease (see Perspective by Gregersen ). Two studies now report on effects stimulating immunological monocytes and dendritic cells with proteins that can elicit a response bacterial or viral infection assess functional links between variants profiles gene expression. M. N. Lee et al. ( 10.1126/science.1246980 ) analyzed expression more than 400 genes, in...
With a rapidly aging global human population, finding cure for late onset neurodegenerative diseases has become an urgent enterprise. However, these efforts are hindered by the lack of understanding what constitutes phenotype aged microglia-the cell type that been strongly implicated genetic studies in pathogenesis age-related disease. Here, we establish set genes is preferentially expressed microglia brain. This HuMi_Aged gene captures unique phenotype, which confirm at protein level....
The skin confers biophysical and immunological protection through a complex cellular network established early in embryonic development. We profiled the transcriptomes of more than 500,000 single cells from developing human fetal skin, healthy adult with atopic dermatitis psoriasis. leveraged these datasets to compare cell states across development, homeostasis, disease. Our analysis revealed an enrichment innate immune during first trimester clonal expansion disease-associated lymphocytes...
Background and objectives Immune checkpoint inhibitor use in oncology is increasing rapidly. We sought to determine the frequency, severity, cause, predictors of AKI a real-world population receiving inhibitors. Design, setting, participants, & measurements included all patients who received therapy from May 2011 December 2016 at Massachusetts General Hospital. Baseline serum creatinine, averaged 6 months before start date, was compared with subsequent creatinine values within 12...
Mechanisms underlying severe coronavirus disease 2019 (COVID-19) remain poorly understood. We analyze several thousand plasma proteins longitudinally in 306 COVID-19 patients and 78 symptomatic controls, uncovering immune non-immune linked to COVID-19. Deconvolution of our proteome data using published scRNA-seq datasets reveals contributions from circulating tissue cells. Sixteen percent display reduced inflammation yet comparably poor outcomes. Comparison who died severely ill survivors...
Increased IFN-α production contributes to the pathogenesis of infectious and autoimmune diseases. Plasmacytoid dendritic cells (pDCs) from females produce more upon TLR7 stimulation than pDCs males, yet mechanisms underlying this difference remain unclear. In article, we show that basal levels IFN regulatory factor (IRF) 5 in were significantly higher compared with males positively correlated percentage IFN-α-secreting pDCs. Delivery recombinant IRF5 protein into human primary increased...
BACKGROUND. SARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19 small-scale cohort studies. The mechanisms behind this association remain elusive.
Asthma is a chronic disease most commonly associated with allergy and type 2 inflammation. However, the mechanisms that link airway inflammation to structural changes define asthma are incompletely understood. Using human model of allergen-induced exacerbation, we compared lower mucosa in allergic asthmatics non-asthmatic controls using single-cell RNA sequencing. In response allergen, asthmatic epithelium was highly dynamic up-regulated genes involved matrix degradation, mucus metaplasia,...
The ability to generate large numbers of distinct types human dendritic cells (DCs) in vitro is critical for accelerating our understanding DC biology and harnessing them clinically. We developed a differentiation method from CD34+ precursors leading high yields plasmacytoid DCs (pDCs) both conventional (cDC1s cDC2s). identity the generated their strong homology blood counterparts were demonstrated by phenotypic, functional, single-cell RNA-sequencing analyses. This culture system revealed...