Luca Bramé
A5030339100- CRISPR and Genetic Engineering
- Genetics, Bioinformatics, and Biomedical Research
- Epigenetics and DNA Methylation
- Science, Research, and Medicine
- DNA Repair Mechanisms
- RNA Interference and Gene Delivery
- Computational Drug Discovery Methods
- Cellular Mechanics and Interactions
- Ultrasound Imaging and Elastography
- Cancer Genomics and Diagnostics
- Microtubule and mitosis dynamics
- Biological Research and Disease Studies
- Cancer, Hypoxia, and Metabolism
- Mitochondrial Function and Pathology
- Genetics and Neurodevelopmental Disorders
- Zebrafish Biomedical Research Applications
- Ubiquitin and proteasome pathways
- Photoacoustic and Ultrasonic Imaging
- Protein Degradation and Inhibitors
Heidelberg University
2021-2024
Charité - Universitätsmedizin Berlin
2022-2024
German Cancer Research Center
2021-2024
Orthopädische Universitätsklinik
2022
DNA amplifications in cancer do not only harbor oncogenes. We sought to determine whether passenger coamplifications could create collateral therapeutic vulnerabilities. Through an analysis of >3,000 genomes followed by the interrogation CRISPR-Cas9 loss-of-function screens across >700 cell lines, we determined that are accompanied distinct dependency profiles. In a proof-of-principle study, demonstrate coamplification bona fide gene DEAD-Box Helicase 1 (DDX1) creates increased on mTOR...
Purpose The zebrafish ( Danio rerio ) has become an important animal model in a wide range of biomedical research disciplines. Growing awareness the role biomechanical properties tumor progression and neuronal development led to increasing interest noninvasive mapping viscoelastic by elastography methods applicable bulky nontranslucent tissues. Methods Microscopic multifrequency MR is introduced for shear wave speed (SWS) loss angle φ as markers stiffness viscosity muscle, brain,...
<p>Overview of the systematic approach to identify collateral lethal dependencies associated with passenger gene coamplifications in cancers.</p>
<p>Overview of the systematic approach to identify collateral lethal dependencies associated with passenger gene coamplifications in cancers.</p>
<p>A proof-of-principle study identifies a selective mTOR pathway dependency in cells with <i>DDX1-MYCN</i> coamplification. <b>A,</b> Correlation between <i>DDX1</i> copy-number and scores (CERES) for <i>RAPTOR</i> neuroblastoma cell lines (Pearson correlation analysis, <i>R</i> = −0.5996, <i>P</i> 0.0152, <i>N</i> 13). <b>B,</b> Western immunoblot of RAPTOR DDX1 the KELLY transduced...
<p>A proof-of-principle study identifies a selective mTOR pathway dependency in cells with <i>DDX1-MYCN</i> coamplification. <b>A,</b> Correlation between <i>DDX1</i> copy-number and scores (CERES) for <i>RAPTOR</i> neuroblastoma cell lines (Pearson correlation analysis, <i>R</i> = −0.5996, <i>P</i> 0.0152, <i>N</i> 13). <b>B,</b> Western immunoblot of RAPTOR DDX1 the KELLY transduced...
<p>DDX1 hijacks the α-KGDH complex resulting in α-KG accumulation and OXPHOS reduction. <b>A,</b> Relative concentrations of α-KG, citrate, isocitrate cancer cell lines with <i>DDX1</i>-<i>MYCN</i> coamplifications (red) compared cells only harboring <i>MYCN</i> amplifications (blue; Welch <i>t</i> test, <i>P</i> = 0.038764, 0.008224, 0.025814 for isocitrate, respectively; <i>N</i> 4 independent...
<p>High DDX1 expression is sufficient to increase sensitivity pharmacologic mTORC1 inhibition <i>in vitro</i> and vivo</i>. <b>A,</b> Relative cell viability of different neuroblastoma lines with <i>DDX1</i>-<i>MYCN</i> coamplification (red, <i>N</i> = 3) or <i>MYCN</i> amplifications (blue, 2) treated rapamycin (2.5 μmol/L for 72 hours) compared after DMSO (vehicle control) treatment (Welch...
<p>Passenger genes are frequently coamplified with oncogenes in cancers and can be associated distinct dependencies. <b>A,</b> The mean number of passenger compared the frequency oncogene amplifications (dot size presents incidence gene coamplification). <b>B,</b> Number cancer cell lines CCLE an amplification coamplification (oncogenes for which sufficient dependency information is available DepMap marked red). <b>C,</b> Chromosome 2 schematic...
<div>Abstract<p>DNA amplifications in cancer do not only harbor oncogenes. We sought to determine whether passenger coamplifications could create collateral therapeutic vulnerabilities. Through an analysis of >3,000 genomes followed by the interrogation CRISPR-Cas9 loss-of-function screens across >700 cell lines, we determined that are accompanied distinct dependency profiles. In a proof-of-principle study, demonstrate coamplification <i>bona fide</i> gene...
<p>DDX1 interacts with α-KGDH complex members, and its interaction is required for mTORC1 pathway activation. <b>A,</b> A schematic of the DDX1 immunoprecipitation (IP) followed by LC-MS/MS. <b>B</b> <b>C,</b> Volcano plot proteins significantly enriched after in KELLY cells harboring <i>MYCN</i> amplifications without <i>DDX1</i> coamplifications (<b>B</b>) IMR5/75 <i>DDX1-MYCN</i>...
<p>DDX1 interacts with α-KGDH complex members, and its interaction is required for mTORC1 pathway activation. <b>A,</b> A schematic of the DDX1 immunoprecipitation (IP) followed by LC-MS/MS. <b>B</b> <b>C,</b> Volcano plot proteins significantly enriched after in KELLY cells harboring <i>MYCN</i> amplifications without <i>DDX1</i> coamplifications (<b>B</b>) IMR5/75 <i>DDX1-MYCN</i>...