A5085071179- Immune Cell Function and Interaction
- Cancer Cells and Metastasis
- Single-cell and spatial transcriptomics
- Cancer-related molecular mechanisms research
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Respiratory Support and Mechanisms
- T-cell and B-cell Immunology
- Neonatal Respiratory Health Research
- interferon and immune responses
- RNA Research and Splicing
- Infant Nutrition and Health
- Genetic Syndromes and Imprinting
- Cancer Immunotherapy and Biomarkers
Harvard University
2023-2025
Boston Children's Hospital
2023-2025
Harvard University Press
2024
University of California, Berkeley
2020-2022
Abstract Cancers display cellular, genetic and epigenetic heterogeneity, complicating disease modeling. Multiple cell states defined by gene expression have been described in lung adenocarcinoma (LUAD). However, the functional contributions of state regulatory programs that control chromatin early stages tumor initiation are not well understood. Using single-cell RNA ATAC sequencing Kras/p53-driven organoids, we identified two major cellular states: one more closely resembling alveolar type...
Mitotically stable random monoallelic gene expression (RME) is documented for a small percentage of autosomal genes. We developed an in vivo genetic model to study the role enhancers RME using high-resolution single-cell analysis natural killer (NK) cell receptor and enhancer deletions mouse germline. Enhancers NK genes were accessible enriched H3K27ac on silent active alleles alike cells sorted according allelic status, suggesting activation status can be decoupled. In with multiple...
Alveolar type 2 (AT2) cells, the epithelial progenitor cells of distal lung, are known to be prominent cell origin for lung adenocarcinoma. The regulatory programs that control chromatin and gene expression in AT2 during early stages tumor initiation not well understood. Here, we dissected response Kras activation p53 loss (KP) using combined single RNA ATAC sequencing an established organoid system. Multi-omic analysis showed KP exhibit two major cellular states: one more closely resembling...
Summary Acute injury in the airways or lung activates local progenitors and stimulates changes cell-cell interactions to restore homeostasis, but it is not appreciated how more distant niches are impacted. We utilized mouse models of airway-specific epithelial examine secondary tissue-wide alveolar, immune, mesenchymal responses. Single-cell transcriptomics vivo validation revealed transient, proliferation alveolar type 2 (AT2) progenitor cells after club cell-specific ablation. The AT2 cell...
Abstract Current cancer immunotherapies are targeted at mobilizing CD8 T cells, although numerous tumors have few or no antigens for lost MHC I, thereby evading cells. There is therefore a need improved therapies that mobilize other immune such as NK to the tumor microenvironment. A recent therapy candidate, cyclic dinucleotide (CDN), activates cGAS-STING pathway of innate system. Intratumoral CDN injections induce type I IFNs and mediators amplify cell response regressions primary tumors....
Abstract Mitotically stable random monoallelic gene expression (RME) is documented for a small percentage of autosomal genes. Here we investigated the role enhancers in RME natural killer (NK) cell receptor Enhancers were accessible and enriched H3K27ac on silent active alleles alike, decoupling enhancer activation expression. controlled frequency, as predicted by binary model action, deletion converted broadly expressed Nkg2d into an gene, recapitulating variegation. The results suggested...