A5059716829- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Single-cell and spatial transcriptomics
- Immune cells in cancer
- Atherosclerosis and Cardiovascular Diseases
- Bioactive Compounds and Antitumor Agents
- Systemic Lupus Erythematosus Research
- T-cell and B-cell Immunology
- Aquaculture disease management and microbiota
- Marine Sponges and Natural Products
- Colorectal Cancer Treatments and Studies
- Diabetes and associated disorders
- Cancer Genomics and Diagnostics
- Chemokine receptors and signaling
- Photochromic and Fluorescence Chemistry
- Echinoderm biology and ecology
- Cytokine Signaling Pathways and Interactions
- Immune Cell Function and Interaction
- bioluminescence and chemiluminescence research
- Gene expression and cancer classification
- Adipokines, Inflammation, and Metabolic Diseases
- Invertebrate Immune Response Mechanisms
- Cell Adhesion Molecules Research
- RNA Research and Splicing
- melanin and skin pigmentation
Broad Institute
2023-2025
MGH Institute of Health Professions
2023-2025
Harvard University
2023-2024
Massachusetts General Hospital
2022-2024
Center for Cancer Research
2024
University of New Haven
2024
Yale University
2024
Massachusetts Institute of Technology
2023
Brown University
2020-2022
Abstract While BRAF inhibitor combinations with EGFR and/or MEK inhibitors have improved clinical efficacy in V600E colorectal cancer (CRC), response rates remain low and lack durability. Preclinical data suggest that BRAF/MAPK pathway inhibition may augment the tumor immune response. We performed a proof-of-concept single-arm phase 2 trial of combined PD-1, sparatlizumab (PDR001), dabrafenib trametinib 37 patients CRC. The primary end point was overall rate, secondary points were...
ABSTRACT The organization of immune cells in human tumors is not well understood. Immunogenic harbor spatially-localized multicellular ‘immunity hubs’ defined by expression the T cell-attracting chemokines CXCL10/CXCL11 and abundant cells. Here, we examined immunity hubs pre-immunotherapy lung cancer specimens, found that they were associated with beneficial responses to PD-1-blockade. Immunity enriched for many interferon-stimulated genes, multiple differentiation states, CXCL9/10/11 +...
Cells bearing pigment have diverse roles and are often under strict evolutionary selection. Here, we explore the regulation of pigmented cells in purple sea urchin Strongylocentrotus purpuratus, an emerging model for function. We took advantage single cell RNA-seq (scRNAseq) technology discovered that embryo segregated into two distinct populations, a mitotic cluster post-mitotic cluster. Gcm is essential expression several genes important function, but only transiently expressed these...
Spatial transcriptomics facilitates gene expression analysis of cells in their spatial anatomical context. Batch effects hinder visualization patterns across samples. We present the Crescendo algorithm to correct for batch at level and enable accurate multiple show Crescendo's utility scalability three datasets ranging from 170,000 7 million single single-cell RNA sequencing technologies. By correcting effects, enhances analyses detect colocalization ligand-receptor interactions enables...
Abstract Resident macrophages and infiltrating monocytes in kidneys of patients with lupus nephritis are altered both frequency function relative to their counterparts healthy kidneys. The extent which mouse models might be useful developing approaches target these cells for treating is poorly understood. Here, we studied four common that share clinical, serologic, histopathologic kidney changes humans. Using single-cell profiling multiplex spatial imaging analyze the intrarenal myeloid...
Abstract Spatial transcriptomics allows for the analysis of a cell’s gene expression in context its physical location. With spatial data, investigators often want to find genes interest whose patterns are biologically relevant multiple samples. However, due confounding factors data that produce noise across samples, datasets, and technologies, it is challenging visualize their We present Crescendo, an integration algorithm performs correction directly on counts reduce variation from...
Abstract Background: Among colorectal cancer (CRC) tumors, mismatch repair deficient (MMRd) tumors have more immunogenic neo-antigens, hence cytotoxic T-cell mediated anti-tumor immunity than proficient (MMRp) tumors. Previously1, we transcriptionally profiled over 300,000 cells from 62 MMRd and MMRp CRC found an MMRd-unique network of immunologically active transcriptional states enriched in interferon-stimulated genes (ISGs). With 4-color imaging, showed that this program arises spatially...
Abstract Background: Our recent clinical trial of combined BRAF, MEK, and PD-1 inhibition showed a 24% response rate in BRAF V600E mutant colon cancer (PMID: 36702949). Analysis epithelial single-cell RNA sequencing data an increase interferon-stimulated genes (ISG) the MAPK pathway responders. organoids also induced ISGs. These suggest synergy between induction immune responses. Methods: We analyzed over 100,000 stromal cells from 23 paired scRNAseq profiles pre- day 15 on-treatment tumor...
Abstract The FcR non-binding anti-CD3 mAb, teplizumab is the first drug approved by FDA to delay Type 1 diabetes (T1D) modulating immune mediated destruction of insulin-producing β cells. However, we and others have observed that after remission induced in diabetic NOD mice are treated with F(ab’)2 fragments mAb 145-2C11, insulitis remains. To understand how antibody induces long-term tolerance, performed single-cell RNA-seq TCR-seq on T cells from islets pancreas-draining lymph nodes (pLN)...
Abstract Background: Immunologic tumor control involves coordination of multiple cell types, but the organization these interactions in human tumors is poorly understood. We recently reported that immunogenic contain spatially-localized multicellular immunity hubs characterized by expression interferon-stimulated genes, including CXCL10/CXCL11 (T attracting chemokines), and presence IFNG+ T cells. This suggested a positive feedback loop where cell-derived IFNγ stimulates production CXCR3...
Resident macrophages and infiltrating monocytes in kidneys of patients with lupus nephritis are altered both frequency function relative to their counterparts healthy kidneys. The extent which mouse models might be useful developing approaches target these cells for treating is poorly understood. Here, we studied four common that share clinical, serologic, histopathologic kidney changes humans. Using single-cell profiling multiplex spatial imaging analyze the intrarenal myeloid compartment...
<h3>Background</h3> Immunologic tumor control involves coordination of multiple cell types, but the organization these interactions in human tumors is poorly understood. We recently reported that immunogenic contain spatially-localized multicellular immunity hubs characterized by expression interferon-stimulated genes, including <i>CXCL10/CXCL11</i> (T attracting chemokines), and presence <i>IFNG</i>+ T cells.<sup>1</sup> This suggested a positive feedback loop where cell-derived IFNγ...