A5051587020- vaccines and immunoinformatics approaches
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Wnt/β-catenin signaling in development and cancer
- T-cell and B-cell Immunology
- Hair Growth and Disorders
- Chronic Lymphocytic Leukemia Research
- Peptidase Inhibition and Analysis
- Monoclonal and Polyclonal Antibodies Research
- CRISPR and Genetic Engineering
- TGF-β signaling in diseases
- Kruppel-like factors research
- RNA and protein synthesis mechanisms
- Advanced Breast Cancer Therapies
- Connective tissue disorders research
- Biosimilars and Bioanalytical Methods
- Viral-associated cancers and disorders
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer-related gene regulation
- FOXO transcription factor regulation
- RNA Research and Splicing
- Skin and Cellular Biology Research
- Developmental Biology and Gene Regulation
- Genomic variations and chromosomal abnormalities
Broad Institute
2019-2024
Howard Hughes Medical Institute
2016-2020
Rockefeller University
2016-2020
McGill University
2010
Abstract Tumor epitopes – peptides that are presented on surface-bound MHC I proteins - provide targets for cancer immunotherapy and have been identified extensively in the annotated protein-coding regions of genome. Motivated by recent discovery translated novel unannotated open reading frames (nuORFs) using ribosome profiling (Ribo-seq), we hypothesized cancer-associated processes could generate nuORFs can serve as a new source tumor antigens harbor somatic mutations or show tumor-specific...
To spatially co-exist and differentially specify fates within developing tissues, morphogenetic cues must be correctly positioned interpreted. Here, we investigate mouse hair follicle development to understand how morphogens operate closely spaced, fate-diverging progenitors. Coupling transcriptomics with genetics, show that emerging progenitors produce both WNTs WNT inhibitors. Surprisingly, however, instead of generating a negative feedback loop, the signals oppositely polarize,...
Activins stimulate FSH synthesis and secretion by pituitary gonadotrope cells. Activin A induction of porcine murine FSHβ (Fshb) gene transcription in immortalized gonadotropes is dependent on homolog Drosophila mothers against decapentaplegic (SMAD) proteins as well the forkhead factor L2 (FOXL2). Using both heterologous homologous cell models, we demonstrate that FOXL2 functionally synergizes with SMAD3/4 to Fshb promoter-reporter activity. We further show endogenous SMAD2/3 physically...
Somatic mutations in cancer cells can generate neoantigens which be recognized by immune and trigger an response. Patients vaccinated with neoantigen-based peptides display expanded neoantigen-specific T cells, suggesting that this could a promising avenue for treatment. Currently, neoantigen predictions are based on detected whole exome sequencing, covers pre-determined set of annotated exons, often falls short cancers few somatic mutations.Ribosome profiling (Ribo-seq), allows to monitor...
Abstract Somatic mutations in cancer cells can generate neoantigens which be recognized by immune and trigger an response. Patients vaccinated with neoantigen-based peptides display expanded neoantigen-specific T cells, suggesting that this could a promising avenue for treatment. Currently, neoantigen predictions are based on detected whole exome sequencing, covers pre-determined set of annotated exons, often falls short cancers few somatic mutations. Ribosome profiling (Ribo-seq), allows to...
Abstract Though CAR T cell therapy has had success treating hematologic malignancies, these treatments have shown only modest efficacy in solid tumors. Little is known about the necessary molecular components required for cytotoxicity, especially context of We investigated role IFNgR signaling on tumors and discovered across tumor types (including glioblastoma, pancreatic, ovarian lung) loss IFNgR1 resulted lower cytotoxicity vitro that this was irrespective target antigen endogenous EGFR,...
Background Chimeric Antigen Receptor (CAR) therapy has had a transformative impact on the treatment of hematologic malignancies 1–6 but success in solid tumors remains elusive. We hypothesized have cell-intrinsic resistance mechanisms to CAR T-cell cytotoxicity. Methods To systematically identify pathways, we conducted genome-wide CRISPR knockout screen glioblastoma cells, disease where T-cells limited efficacy. 7 8 utilized cell line U87 and targeted endogenously expressed EGFR with...