A5082430052- CRISPR and Genetic Engineering
- Crustacean biology and ecology
- Galectins and Cancer Biology
- Protein Tyrosine Phosphatases
- Virus-based gene therapy research
- CAR-T cell therapy research
- Aquaculture Nutrition and Growth
- Neurobiology and Insect Physiology Research
- Single-cell and spatial transcriptomics
- Regulation of Appetite and Obesity
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Innovative Microfluidic and Catalytic Techniques Innovation
- Pluripotent Stem Cells Research
- Immune cells in cancer
- Physiological and biochemical adaptations
- Immune Cell Function and Interaction
- Cancer, Hypoxia, and Metabolism
- Cancer Immunotherapy and Biomarkers
- Glioma Diagnosis and Treatment
- Heart Rate Variability and Autonomic Control
- Aquatic life and conservation
- T-cell and B-cell Immunology
- Adrenal and Paraganglionic Tumors
- Neuropeptides and Animal Physiology
Broad Institute
2022-2023
Massachusetts General Hospital
2023
Center for Cancer Research
2023
Bowdoin College
2021-2022
Abstract Immune checkpoint blockade is effective for some patients with cancer, but most are refractory to current immunotherapies and new approaches needed overcome resistance 1,2 . The protein tyrosine phosphatases PTPN2 PTPN1 central regulators of inflammation, their genetic deletion in either tumour cells or immune promotes anti-tumour immunity 3–6 However, challenging drug targets; particular, the active site has been considered undruggable. Here we present discovery characterization...
Abstract CAR-T therapy is a promising, novel treatment modality for B-cell malignancies and yet many patients relapse through variety of means, including loss cells antigen escape. To investigate leukemia-intrinsic resistance mechanisms, we performed genome-wide CRISPR-Cas9 loss-of-function screens in an immunocompetent murine model acute lymphoblastic leukemia (B-ALL) utilizing modular guide RNA library. We identified IFN γ R/JAK/STAT signaling components processing presentation pathway as...
Recognition of Cas9 and other proteins encoded in delivery vectors has limited CRISPR technology vivo. Here, we present a protocol for genome engineering using selective antigen removal (SCAR) lentiviral Renca mouse model. This describes how to conduct an vivo genetic screen with sgRNA library SCAR that can be applied different cell lines contexts. For complete details on the use execution this protocol, please refer Dubrot et al. (2021).1.
Central pattern generators produce rhythmic behaviors independently of sensory input; however, their outputs can be modulated by neuropeptides, thereby allowing for functional flexibility. We investigated the effects C-type allatostatins (AST-C) on cardiac ganglion (CG), which is central generator that controls heart American lobster, Homarus americanus, to identify biological mechanism underlying significant variability in individual responses AST-C. proposed presence multiple receptors,...
<h3>Background</h3> Immune checkpoint blockade is effective for a subset of patients across many cancers, but most are refractory to current immunotherapies and new approaches needed overcome resistance.<sup>1 2</sup> The protein tyrosine phosphatase PTPN2 the closely related PTPN1 central regulators inflammation, their genetic deletion in either tumor cells or host immune promotes anti-tumor immunity.<sup>3–6</sup> However, phosphatases challenging drug targets particular, active site has...
<h3>Background</h3> The tyrosine phosphatases PTPN2 and PTPN1 negatively regulate several signaling pathways in immune tumor cells. We previously demonstrated that oral administration of our recently discovered active site PTPN2/N1 small molecule inhibitor ABBV-CLS-484 (AC-484) promotes anti-tumor immunity syngeneic mouse models. AC-484 improves T cell activation function upon TCR stimulation enhances dendritic macrophage activity <i>in vitro</i> consistent with prior findings or genetically...
Neuronal responses to peptide signaling are determined by the specific binding of a its receptor(s). For example, isoforms same family can drive distinct in circuit having different affinities for receptor, each isoform bind or combination these scenarios. Small changes composition alter kinetics and overall physiological response given peptide. In American lobster ( Homarus americanus ), native C-type allatostatins (AST-Cs) usually decrease heartbeat frequency contraction force. However,...
Abstract The immune system can eliminate tumors, but checkpoints enable tumors to escape destruction. Here, we report the systematic identification of evasion mechanisms using genome-scale in vivo CRISPR screens eight murine cancer models treated with checkpoint blockade (ICB). We identify and validate previously unreported genes key inhibitory that have a conserved role across several models, such as non-classical MHC-I molecule Qa-1b/HLA-E, which scores top overall sensitizing hit all...