A5057286638- Chronic Myeloid Leukemia Treatments
- Protease and Inhibitor Mechanisms
- Signaling Pathways in Disease
- Ubiquitin and proteasome pathways
- Eosinophilic Disorders and Syndromes
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Chronic Lymphocytic Leukemia Research
- Cancer Mechanisms and Therapy
- PARP inhibition in cancer therapy
- Health, Environment, Cognitive Aging
- CAR-T cell therapy research
- Blood Coagulation and Thrombosis Mechanisms
- Cytokine Signaling Pathways and Interactions
- Quinazolinone synthesis and applications
- Platelet Disorders and Treatments
- Kruppel-like factors research
- Cell Adhesion Molecules Research
- RNA modifications and cancer
- Innovation Policy and R&D
- Radiation Therapy and Dosimetry
- Fibroblast Growth Factor Research
- Cancer-related gene regulation
- Click Chemistry and Applications
- Immune Cell Function and Interaction
- Peptidase Inhibition and Analysis
Tango Therapeutics (United States)
2022-2024
Tufts Medical Center
2005-2014
Molecular Oncology (United States)
2005-2014
Molecular Research Institute
2008
Background A somatic activating mutation (V617F) in the JAK2 tyrosine kinase was recently discovered majority of patients with polycythemia vera (PV), and some essential thrombocythemia (ET) chronic idiopathic myelofibrosis. However, role mutant disease pathogenesis is unclear. Methods Findings We expressed murine WT or V617F via retroviral bone marrow transduction/transplantation hematopoietic system two different inbred mouse strains, Balb/c C57Bl/6 (B6). In both V617F, but not WT, induced...
Protease-activated receptor-2 (PAR2), a cell surface receptor for trypsin-like proteases, plays key role in number of acute and chronic inflammatory diseases the joints, lungs, brain, gastrointestinal tract, vascular systems. Despite considerable effort by pharmaceutical industry, PAR2 has proven recalcitrant to targeting small molecule inhibitors, which have been unable effectively prevent interaction protease-generated tethered ligand with body receptor. Here, we report development...
Gene chip and proteomic analyses of tumors stromal tissue has led to the identification dozens candidate tumor host components potentially involved in tumor-stromal interactions, angiogenesis, progression invasive disease. In particular, matrix metalloproteases (MMP) have emerged as important biomarkers prognostic factors for metastatic cancers. From an initial screen benign versus malignant patient fluids, we delineated a metalloprotease cascade comprising MMP-14, MMP-9, MMP-1 that...
Abstract CRISPR Cas9-based screening is a powerful approach for identifying and characterizing novel drug targets. Here, we elucidate the synthetic lethal mechanism of deubiquitinating enzyme USP1 in cancers with underlying DNA damage vulnerabilities, specifically BRCA1/2 mutant tumors subset wild-type (WT) tumors. In sensitive cells, pharmacologic inhibition leads to decreased synthesis concomitant S-phase–specific damage. Genome-wide CRISPR-Cas9 screens identify RAD18 UBE2K, which promote...
Sensorineural hearing loss is prevalent within society affecting the quality of life 460 million worldwide. In majority cases, this due to insult or degeneration mechanosensory hair cells in cochlea. adult mammals, cell irreversible as sensory are not replaced spontaneously. Genetic inhibition Notch signaling had been shown induce formation by transdifferentiation supporting young postnatal rodents and provided an impetus for targeting pathway with small molecule inhibitors restoration....
Abstract TNG348 is a selective and potent inhibitor of the deubiquitinating enzyme USP1 specifically designed to target BRCA1/2mut vulnerabilities in breast ovarian tumors. Here we present biochemical, mechanistic, vitro vivo characterization TNG348, an oral, allosteric highly USP1. Upon treatment, causes loss viability panel cancer cell lines displays dose-dependent tumor growth inhibition xenograft models. Furthermore, activity extends beyond models with PARP (PARPi) sensitivity...
Abstract CRISPR-based functional genomics screening can be designed to identify novel cancer cell intrinsic targets that increase tumor immunogenicity. Using a FACS-based CRISPR sorting screen for PD-L1 expression, we identified Euchromatic histone-lysine-N-methyltransferase 1 and 2 (EHMT1/2) as negative modulators of the interferon signaling pathways. EHMT1 EHMT2 are histone methyltransferases mono- di-methylate lysine 9 H3 repress gene transcription defined target genes. Gene knockout or...
<h3>Background</h3> CRISPR-based functional genomics screening can be designed to identify novel cancer cell intrinsic targets that increase tumor immunogenicity. Using a FACS-based CRISPR sorting screen for PD-L1 expression, we identified euchromatic histone-lysine-N-methyltransferase 1 and 2 (EHMT1/2) as negative modulators of the interferon signaling pathways. EHMT1 EHMT2 are histone methyltransferases mono- di-methylate lysine 9 H3 repress gene transcription defined target genes. A...
<div>Abstract<p>Gene chip and proteomic analyses of tumors stromal tissue has led to the identification dozens candidate tumor host components potentially involved in tumor-stromal interactions, angiogenesis, progression invasive disease. In particular, matrix metalloproteases (MMP) have emerged as important biomarkers prognostic factors for metastatic cancers. From an initial screen benign versus malignant patient fluids, we delineated a metalloprotease cascade comprising...
Supplementary Fig. S1 from Targeting a metalloprotease-PAR1 signaling system with cell-penetrating pepducins inhibits angiogenesis, ascites, and progression of ovarian cancer
Supplementary Fig. S4 from Targeting a metalloprotease-PAR1 signaling system with cell-penetrating pepducins inhibits angiogenesis, ascites, and progression of ovarian cancer
Supplementary Fig. S2 from Targeting a metalloprotease-PAR1 signaling system with cell-penetrating pepducins inhibits angiogenesis, ascites, and progression of ovarian cancer
<div>Abstract<p>Gene chip and proteomic analyses of tumors stromal tissue has led to the identification dozens candidate tumor host components potentially involved in tumor-stromal interactions, angiogenesis, progression invasive disease. In particular, matrix metalloproteases (MMP) have emerged as important biomarkers prognostic factors for metastatic cancers. From an initial screen benign versus malignant patient fluids, we delineated a metalloprotease cascade comprising...