A5056041031- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- T-cell and B-cell Immunology
- Cancer Cells and Metastasis
- Immune Cell Function and Interaction
- Cancer Immunotherapy and Biomarkers
- Pancreatic and Hepatic Oncology Research
- Natural Language Processing Techniques
- Music and Audio Processing
- Pluripotent Stem Cells Research
- Gene Regulatory Network Analysis
- Speech Recognition and Synthesis
- Cancer Research and Treatments
- Epigenetics and DNA Methylation
- CAR-T cell therapy research
- Circadian rhythm and melatonin
- Immune cells in cancer
- Cancer, Stress, Anesthesia, and Immune Response
- RNA modifications and cancer
- Cell Image Analysis Techniques
- RNA and protein synthesis mechanisms
- Gene expression and cancer classification
- Mitochondrial Function and Pathology
- CRISPR and Genetic Engineering
- Developmental Biology and Gene Regulation
New York Genome Center
2020-2025
Memorial Sloan Kettering Cancer Center
2017-2025
Kettering University
2018-2025
Howard Hughes Medical Institute
2025
Carnegie Mellon University
2022-2023
Varian Medical Systems (United States)
2020
Columbia University
2014-2019
Yale Cancer Center
2019
Yale University
2017-2019
Williams College
2016
Immune checkpoint blockade therapy targets T cell-negative costimulatory molecules such as cytotoxic lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1). Combination anti–CTLA-4 anti–PD-1 has enhanced efficacy, but it remains unclear through what mechanisms effects are mediated. A critical question is whether combination modulates the same populations monotherapies. Using a mass cytometry-based systems approach, we comprehensively profiled response of to monotherapy plus in...
Abstract Metacells are cell groupings derived from single-cell sequencing data that represent highly granular, distinct states. Here we present aggregation of states (SEACells), an algorithm for identifying metacells overcome the sparsity while retaining heterogeneity obscured by traditional clustering. SEACells outperforms existing algorithms in comprehensive, compact and well-separated both RNA assay transposase-accessible chromatin (ATAC) modalities across datasets with discrete types...
Abstract The most prominent homozygous deletions in cancer affect chromosome 9p21.3 and eliminate CDKN2A/B tumor suppressors, disabling a cell-intrinsic barrier to tumorigenesis. Half of deletions, however, also encompass type I interferon (IFN) gene cluster; the consequences this co-deletion remain unexplored. To functionally dissect other large genomic we developed flexible deletion engineering strategy, MACHETE (molecular alteration chromosomes with engineered tandem elements). Applying...
As cancers progress, they become increasingly aggressive—metastatic tumours are less responsive to first-line therapies than primary tumours, acquire resistance successive and eventually cause death1,2. Mutations largely conserved between metastatic from the same patients, suggesting that non-genetic phenotypic plasticity has a major role in cancer progression therapy resistance3–5. However, we lack an understanding of cell states mechanisms by which transition. Here, cohort biospecimen...
Abstract The thymus is essential for establishing adaptive immunity yet undergoes age-related involution that leads to compromised immune responsiveness. also extremely sensitive acute insult and although capable of regeneration, this capacity declines with age unknown reasons. We applied single-cell spatial transcriptomics, lineage-tracing advanced imaging define changes in nonhematopoietic stromal cells discovered the emergence two atypical thymic epithelial cell (TEC) states. These...
ABSTRACT Single-cell RNA-sequencing is fast becoming a major technology that revolutionizing biological discovery in fields such as development, immunology and cancer. The ability to simultaneously measure thousands of genes at single cell resolution allows, among other prospects, for the possibility learning gene regulatory networks large scales. However, scRNA-seq technologies suffer from many sources significant technical noise, most prominent which ‘dropout’ due inefficient mRNA capture....
Abstract While regulatory T (T reg ) cells are traditionally viewed as professional suppressors of antigen presenting and effector in both autoimmunity cancer, recent findings distinct cell functions tissue maintenance suggest that their purview extends to a wider range is broader than previously assumed. To elucidate tumoral ‘connectivity’ diverse tumor-supporting accessory types, we explored immediate early changes single-cell transcriptomes upon punctual depletion experimental lung cancer...
Thymic injury associated with disease or cancer treatment reduces T cell production and makes patients more vulnerable to infections cancers. Here, we examined the role of regulatory (Treg) cells on thymic regeneration. Treg frequencies increased in thymus various acute models. Depletion impaired regeneration, impacting both thymocyte compartment stromal compartment; adoptive transfer enhanced Expansion circulating cells, as opposed that tissue resident recent emigrants, explained this...
The female mosquito's remarkable ability to hunt humans and transmit pathogens relies on her unique biology. Here, we present the Mosquito Cell Atlas (MCA), a comprehensive single-nucleus RNA sequencing dataset of more than 367,000 nuclei from 19 dissected tissues adult male Aedes aegypti , providing cellular-level resolution mosquito We identify novel cell types expand our understanding sensory neuron organization chemoreceptors all tissues. Our analysis uncovers male-specific cells...
IntroductionThis study aimed to characterize the tumor-infiltrating immune cells population in Kras/tumor protein 53 (Trp53)-driven lung tumors and evaluate combinatorial antitumor effect with MEK inhibitor (MEKi), trametinib, immunomodulatory monoclonal antibodies (mAbs) targeting either programmed death -1 (PD-1) or cell ligand 1 (PD-L1) vivo.MethodsTrp53FloxFlox;KrasG12D/+;Rosa26LSL-Luciferase/LSL-Luciferase (PKL) genetically engineered mice were used develop autochthonous intratracheal...
Human papillomavirus (HPV)-negative head and neck squamous cell carcinomas (HNSCC) commonly bear disruptive mutations in TP53, resulting treatment resistance. In these patients, direct targeting of p53 has not been successful, but synthetic lethal approaches have promise. Although Aurora A kinase (AURKA) is overexpressed an oncogenic driver, its inhibition only modest clinical effects HPV-negative HNSCC. We explored a novel combination AURKA WEE1 to overcome intrinsic resistance...
Radial glia (RG) cells are the first neural stem to appear during embryonic development. Adult human glioblastomas harbor a subpopulation of RG-like with typical RG morphology and markers. The exhibit classic unique mitotic behavior normal in cell-autonomous manner. Single-cell RNA sequencing analyses glioblastoma reveal transcriptionally dynamic clusters that share profiles fetal radial reside quiescent cycling states. Functional assays show role for interleukin triggering exit from...
Metastasis is the principal cause of cancer death, yet we lack an understanding metastatic cell states, their relationship to primary tumor and mechanisms by which they transition. In a cohort biospecimen trios from same-patient normal colon, colorectal cancer, show that while tumors largely adopt LGR5 + intestinal stem-like metastases display progressive plasticity. Loss states accompanied reprogramming into highly conserved fetal progenitor state, followed non-canonical differentiation...
Single-cell RNA-sequencing is revolutionizing biological discovery. However, scRNA-seq technologies suffer from many sources of significant technical noise, the most prominent being undersampling mRNA molecules, often termed 'dropout'. Dropout can severely obscure important gene-gene relationships and impedes possibility learning gene regulatory networks at single cell resolution. To address this, we developed MAGIC (Markov Affinity-based Graph Imputation Cells), a computational approach...
Regulatory T (Treg) cells prevent autoimmunity by limiting immune responses and inflammation in the secondary lymphoid organs nonlymphoid tissues. While unique subsets of Treg have been described some tissues, their relationship to circulation remains unclear. Furthermore, it is possible that from similar tissue types share largely properties. We identified a short-lived effector cell subset expresses α2 integrin, CD49b, exhibits distribution, being abundant peripheral blood, vasculature,...
Despite the benefits of chimeric antigen receptor (CAR)-T cell therapies against lymphoid malignancies, responses in solid tumors have been more limited and off-target toxicities marked. Among possible design limitations CAR-T cells for cancer are unwanted tonic (antigen-independent) signaling activation. Efforts to overcome these hurdles blunted by a lack mechanistic understanding. Here, we showed that single-cell analysis with time course mass cytometry provided rapid means assessing We...
Heterogeneity is a hallmark of cancer. The advent single-cell technologies has helped uncover heterogeneity in high-throughput manner different cancers across varied contexts. Here we apply sequencing to reveal inherent assumptively monoclonal pancreatic cancer (PDAC) cell lines and patient-derived organoids (PDOs). Our findings high degree both genomic transcriptomic polyclonality monolayer PDAC lines, custodial variation induced by growing apparently identical laboratories, shifts...
Speech summarization is typically performed by using a cascade of speech recognition and text models. End-to-end modeling models challenging due to memory compute constraints arising from long input audio sequences. Recent work in document has inspired methods reduce the complexity self-attentions, which enables transformer handle In this work, we introduce single model optimized end-to-end for summarization. We apply restricted self-attention technique text-based address constraints....