A5072342016- Nuclear Structure and Function
- Ubiquitin and proteasome pathways
- Chromatin Remodeling and Cancer
- Sarcoma Diagnosis and Treatment
- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Neuroblastoma Research and Treatments
- Microtubule and mitosis dynamics
- PARP inhibition in cancer therapy
- RNA Research and Splicing
- Cancer Genomics and Diagnostics
- Radiation Therapy and Dosimetry
- Cancer-related Molecular Pathways
- Genetics and Neurodevelopmental Disorders
- Health, Environment, Cognitive Aging
- Chromosomal and Genetic Variations
- Innovation Policy and R&D
- RNA modifications and cancer
- Legal and Social Justice Studies
- Advanced biosensing and bioanalysis techniques
- Protein Degradation and Inhibitors
- Regional Development and Environment
- Genomic variations and chromosomal abnormalities
- Medical Imaging Techniques and Applications
The University of Texas Southwestern Medical Center
2022-2024
Tango Therapeutics (United States)
2021-2023
Southwestern Medical Center
2022
University of South Florida
2021
Complex genome rearrangements can be generated by the catastrophic pulverization of missegregated chromosomes trapped within micronuclei through a process known as chromothripsis
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...
Abstract Synthetic lethality is a genetic interaction that results in cell death when two deficiencies co-occur but not either deficiency occurs alone, which can be co-opted for cancer therapeutics. Pairs of paralog genes are among the most straightforward potential synthetic–lethal interactions by virtue their redundant functions. Here, we demonstrate paralog-based synthetic targeting vaccinia-related kinase 1 (VRK1) glioblastoma (GBM) deficient VRK2, silenced promoter methylation...
Abstract Mitotic errors generate micronuclei entrapping mis-segregated chromosomes, which are susceptible to catastrophic fragmentation through chromothripsis. The reassembly of fragmented chromosomes by error-prone DNA double-strand break (DSB) repair generates diverse genomic rearrangements associated with human diseases. How specific pathways recognize and process these lesions remains poorly understood. Here we use CRISPR/Cas9 systematically inactivate distinct DSB interrogate the...
Replication stress response ensures impediments to DNA replication do not compromise fork stability and genome integrity. In a process termed protection, newly synthesized at stalled forks is stabilized protected from nuclease-mediated degradation. We report the identification of DDB1- CUL4-associated factor 14 (DCAF14), substrate receptor for Cullin4-RING E3 ligase (CRL4) complex, integral in stabilizing forks. DCAF14 localizes rapidly promotes integrity by preventing collapse into...
ABSTRACT Errors in mitosis can generate micronuclei that entrap mis-segregated chromosomes, which are susceptible to catastrophic fragmentation through a process termed chromothripsis. The reassembly of fragmented chromosomes by error-prone DNA double-strand break (DSB) repair generates spectrum simple and complex genomic rearrangements associated with human cancers disorders. How specific DSB pathways recognize these lesions remains poorly understood. Here we used CRISPR/Cas9 systematically...
ABSTRACT Synthetic lethality — a genetic interaction that results in cell death when two deficiencies co-occur but not either deficiency occurs alone can be co-opted for cancer therapeutics. A pair of paralog genes is among the most straightforward synthetic lethal by virtue their redundant functions. Here we demonstrate paralog-based targeting Vaccinia-Related Kinase 1 (VRK1) 2 (VRK2)-methylated glioblastoma (GBM). VRK2 silenced promoter methylation approximately two-thirds GBM, an...
<div>Abstract<p>Synthetic lethality is a genetic interaction that results in cell death when two deficiencies co-occur but not either deficiency occurs alone, which can be co-opted for cancer therapeutics. Pairs of paralog genes are among the most straightforward potential synthetic–lethal interactions by virtue their redundant functions. Here, we demonstrate paralog-based synthetic targeting vaccinia-related kinase 1 (VRK1) glioblastoma (GBM) deficient VRK2, silenced promoter...
Supplementary Data from VRK1 Is a Synthetic–Lethal Target in VRK2-Deficient Glioblastoma
Supplementary Figure from VRK1 Is a Synthetic–Lethal Target in VRK2-Deficient Glioblastoma
Supplementary Data from VRK1 Is a Synthetic–Lethal Target in VRK2-Deficient Glioblastoma
Supplementary Data from VRK1 Is a Synthetic–Lethal Target in VRK2-Deficient Glioblastoma
Supplementary Data from VRK1 Is a Synthetic–Lethal Target in VRK2-Deficient Glioblastoma
Supplementary Data from VRK1 Is a Synthetic–Lethal Target in VRK2-Deficient Glioblastoma
Supplementary Data from VRK1 Is a Synthetic–Lethal Target in VRK2-Deficient Glioblastoma
Supplementary Data from VRK1 Is a Synthetic–Lethal Target in VRK2-Deficient Glioblastoma
Supplementary Figure from VRK1 Is a Synthetic–Lethal Target in VRK2-Deficient Glioblastoma
Supplementary Data from VRK1 Is a Synthetic–Lethal Target in VRK2-Deficient Glioblastoma
<p>I-138 inhibits USP1-UAF1 - related to Figure 1</p>
<p>CRISPR-UMI analysis and characterization of PCNA dynamics - related to Figure 3</p>
<p>I-138 activity in BRCA1/2 WT and mutant cells - related to Figure 2</p>
<p>USP1 and PARP inhibition are synergistic in a BRCA1/2-dependent manner - related to Figure 4</p>