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Book ; Thesis: gh130-dependent pathways in host hepatocytes are important for liver repopulation in mice

Tschaharganeh, Darjus-Felix

2010

Author's details	vorgelegt von Darjus-Felix Tschaharganeh
Language	English
Size	36 S. : Ill., graph. Darst.
Publishing country	Germany
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Aachen, Techn. Hochsch., Diss., 2010
HBZ-ID	HT016327058
Database	Catalogue ZB MED Medicine, Health

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Article ; Online: MLL3 regulates the

Zhu, Changyu / Soto-Feliciano, Yadira M / Morris, John P / Huang, Chun-Hao / Koche, Richard P / Ho, Yu-Jui / Banito, Ana / Chen, Chun-Wei / Shroff, Aditya / Tian, Sha / Livshits, Geulah / Chen, Chi-Chao / Fennell, Myles / Armstrong, Scott A / Allis, C David / Tschaharganeh, Darjus F / Lowe, Scott W

eLife

2023 Volume 12

Abstract: Mutations in genes encoding components of chromatin modifying and remodeling complexes are among the most frequently observed somatic events in human cancers. For example, missense and nonsense mutations targeting the mixed lineage leukemia family member ...

Abstract	Mutations in genes encoding components of chromatin modifying and remodeling complexes are among the most frequently observed somatic events in human cancers. For example, missense and nonsense mutations targeting the mixed lineage leukemia family member 3 (MLL3, encoded by
MeSH term(s)	Humans ; Animals ; Mice ; Liver Neoplasms/genetics ; Liver Neoplasms/pathology ; Tumor Suppressor Protein p14ARF/genetics ; Carcinoma, Hepatocellular/genetics ; Carcinoma, Hepatocellular/pathology ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; Chromatin ; Carcinogenesis
Chemical Substances	Tumor Suppressor Protein p14ARF ; Cyclin-Dependent Kinase Inhibitor p16 ; Chromatin ; CDKN2A protein, human
Language	English
Publishing date	2023-06-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.80854
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Coordinated Tumor Suppression by Chromosome 8p.

Tschaharganeh, Darjus F / Bosbach, Benedikt / Lowe, Scott W

Cancer cell

2016 Volume 29, Issue 5, Page(s) 617–619

Abstract: In this issue of Cancer Cell, Cai et al. use genome editing to study 8p deletions in a mammary epithelial cell model and show that 8p loss of heterozygosity (LOH) attenuates the action of several genes that collectively promote cell invasion and enhance ... ...

Abstract	In this issue of Cancer Cell, Cai et al. use genome editing to study 8p deletions in a mammary epithelial cell model and show that 8p loss of heterozygosity (LOH) attenuates the action of several genes that collectively promote cell invasion and enhance cellular sensitivity to autophagy inhibitors.
MeSH term(s)	Chromosome Deletion ; Chromosome Mapping ; Genes, Tumor Suppressor ; Humans ; Loss of Heterozygosity ; Neoplasms/genetics
Language	English
Publishing date	2016-05-10
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2078448-X
ISSN	1878-3686 ; 1535-6108
ISSN (online)	1878-3686
ISSN	1535-6108
DOI	10.1016/j.ccell.2016.04.011
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Zs.A 5650: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 104: Show issues

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Article ; Online: Using CRISPR/Cas to study gene function and model disease in vivo.

Tschaharganeh, Darjus F / Lowe, Scott W / Garippa, Ralph J / Livshits, Geulah

The FEBS journal

2016 Volume 283, Issue 17, Page(s) 3194–3203

Abstract: The recent discovery of the CRISPR/Cas system and repurposing of this technology to edit a variety of different genomes have revolutionized an array of scientific fields, from genetics and translational research, to agriculture and bioproduction. In ... ...

Abstract	The recent discovery of the CRISPR/Cas system and repurposing of this technology to edit a variety of different genomes have revolutionized an array of scientific fields, from genetics and translational research, to agriculture and bioproduction. In particular, the prospect of rapid and precise genome editing in laboratory animals by CRISPR/Cas has generated an immense interest in the scientific community. Here we review current in vivo applications of CRISPR/Cas and how this technology can improve our knowledge of gene function and our understanding of biological processes in animal models.
MeSH term(s)	Animals ; CRISPR-Cas Systems ; Chromosome Aberrations ; DNA End-Joining Repair ; Disease Models, Animal ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/metabolism ; Epigenetic Repression ; Gene Editing/methods ; Germ-Line Mutation ; Humans ; Mice ; Models, Genetic ; Transcriptional Activation
Language	English
Publishing date	2016-06-16
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.13750
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Article ; Online: Multiplexed orthogonal genome editing and transcriptional activation by Cas12a.

Breinig, Marco / Schweitzer, Anabel Y / Herianto, Anna M / Revia, Steffie / Schaefer, Lisa / Wendler, Lena / Cobos Galvez, Ana / Tschaharganeh, Darjus F

Nature methods

2018 Volume 16, Issue 1, Page(s) 51–54

Abstract: CRISPR-Cas9-based combinatorial perturbation approaches for orthogonal knockout and gene activation have been impeded by complex vector designs and co-delivery of multiple constructs. Here, we demonstrate that catalytically active CRISPR-Cas12a fused to ... ...

Abstract	CRISPR-Cas9-based combinatorial perturbation approaches for orthogonal knockout and gene activation have been impeded by complex vector designs and co-delivery of multiple constructs. Here, we demonstrate that catalytically active CRISPR-Cas12a fused to a transcriptional-activator domain enables flexible switching between genome editing and transcriptional activation by altering guide length. By leveraging Cas12a-mediated CRISPR-RNA array processing, we illustrate that Cas12a-VPR enables simplified multiplexed knockout and transcriptional activation in vitro and in vivo.
MeSH term(s)	Animals ; CRISPR-Cas Systems ; Cell Line, Tumor ; Gene Editing ; HEK293 Cells ; Humans ; Mice ; Transcriptional Activation
Language	English
Publishing date	2018-12-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2169522-2
ISSN	1548-7105 ; 1548-7091
ISSN (online)	1548-7105
ISSN	1548-7091
DOI	10.1038/s41592-018-0262-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A Pipeline for Drug Target Identification and Validation.

Manchado, Eusebio / Huang, Chun-Hao / Tasdemir, Nilgun / Tschaharganeh, Darjus F / Wilkinson, John E / Lowe, Scott W

Cold Spring Harbor symposia on quantitative biology

2017 Volume 81, Page(s) 257–267

Abstract: Rapid and affordable tumor profiling has led to an explosion of genomic data that is facilitating the development of new cancer therapies. The potential of therapeutic strategies aimed at inactivating the oncogenic lesions that contribute to the aberrant ...

Abstract	Rapid and affordable tumor profiling has led to an explosion of genomic data that is facilitating the development of new cancer therapies. The potential of therapeutic strategies aimed at inactivating the oncogenic lesions that contribute to the aberrant survival and proliferation of tumor cells has yielded remarkable success in some malignancies such as BRAF-mutant melanoma and BCR-ABL expressing chronic myeloid leukemia. However, the direct inhibition of several well-established oncoproteins in some of these cancers is not possible or produces only transient benefits. Functional genomics represents a powerful approach for the identification of vulnerabilities linked to specific genetic alterations and has provided substantial insights into cancer signaling networks. Still, as inhibition of gene function can have diverse effects on both tumor and normal tissues, information on the potency of target inhibition on tumor growth as well as the toxic side effects of target inhibition are also needed. Here, we discuss our RNA interference (RNAi) pipeline for cancer target discovery based on our optimized short-hairpin RNA (shRNA) tools for negative selection screens and inducible RNAi platform that, in combination with embryonic stem cell (ESC)-based genetically engineered mouse models (GEMMs), enable deep in vivo target validation.
MeSH term(s)	Animals ; Cell Proliferation/genetics ; Disease Models, Animal ; Embryonic Stem Cells/cytology ; Humans ; RNA Interference/physiology ; RNA, Small Interfering/genetics ; Signal Transduction/genetics
Chemical Substances	RNA, Small Interfering
Language	English
Publishing date	2017-01-05
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ISSN	1943-4456 ; 0091-7451
ISSN (online)	1943-4456
ISSN	0091-7451
DOI	10.1101/sqb.2016.81.031096
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Using CRISPR/Cas to study gene function and model disease in vivo

Tschaharganeh, Darjus F / Geulah Livshits / Ralph J. Garippa / Scott W. Lowe

FEBS journal. 2016 Sept., v. 283, no. 17

2016

Abstract	The recent discovery of the CRISPR/Cas system and repurposing of this technology to edit a variety of different genomes have revolutionized an array of scientific fields, from genetics and translational research, to agriculture and bioproduction. In particular, the prospect of rapid and precise genome editing in laboratory animals by CRISPR/Cas has generated an immense interest in the scientific community. Here we review current in vivo applications of CRISPR/Cas and how this technology can improve our knowledge of gene function and our understanding of biological processes in animal models.
Keywords	animal models ; disease models ; genes ; genetics ; laboratory animals
Language	English
Dates of publication	2016-09
Size	p. 3194-3203.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	REVIEW
ZDB-ID	2173655-8
ISSN	1742-4658 ; 1742-464X
ISSN (online)	1742-4658
ISSN	1742-464X
DOI	10.1111/febs.13750
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: A preclinical platform for assessing antitumor effects and systemic toxicities of cancer drug targets.

Proceedings of the National Academy of Sciences of the United States of America

2022 Volume 119, Issue 17, Page(s) e2110557119

Abstract: Anticancer drug development campaigns often fail due to an incomplete understanding of the therapeutic index differentiating the efficacy of the agent against the cancer and its on-target toxicities to the host. To address this issue, we established a ... ...

Abstract	Anticancer drug development campaigns often fail due to an incomplete understanding of the therapeutic index differentiating the efficacy of the agent against the cancer and its on-target toxicities to the host. To address this issue, we established a versatile preclinical platform in which genetically defined cancers are produced using somatic tissue engineering in transgenic mice harboring a doxycycline-inducible short hairpin RNA against the target of interest. In this system, target inhibition is achieved by the addition of doxycycline, enabling simultaneous assessment of efficacy and toxicity in the same animal. As proof of concept, we focused on CDK9—a cancer target whose clinical development has been hampered by compounds with poorly understood target specificity and unacceptable toxicities. We systematically compared phenotypes produced by genetic Cdk9 inhibition to those achieved using a recently developed highly specific small molecule CDK9 inhibitor and found that both perturbations led to robust antitumor responses. Remarkably, nontoxic levels of CDK9 inhibition could achieve significant treatment efficacy, and dose-dependent toxicities produced by prolonged CDK9 suppression were largely reversible upon Cdk9 restoration or drug withdrawal. Overall, these results establish a versatile in vivo target validation platform that can be employed for rapid triaging of therapeutic targets and lend support to efforts aimed at advancing CDK9 inhibitors for cancer therapy.
MeSH term(s)	Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Cyclin-Dependent Kinase 9/metabolism ; Mice ; Neoplasms/drug therapy ; Neoplasms/genetics ; RNA Interference
Chemical Substances	Antineoplastic Agents ; Cdk9 protein, mouse (EC 2.7.11.22) ; Cyclin-Dependent Kinase 9 (EC 2.7.11.22)
Language	English
Publishing date	2022-04-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2110557119
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Chelator-Free Radiolabeling of SERRS Nanoparticles for Whole-Body PET and Intraoperative Raman Imaging.

Wall, Matthew A / Shaffer, Travis M / Harmsen, Stefan / Tschaharganeh, Darjus-Felix / Huang, Chun-Hao / Lowe, Scott W / Drain, Charles Michael / Kircher, Moritz F

Theranostics

2017 Volume 7, Issue 12, Page(s) 3068–3077

Abstract: A single contrast agent that offers whole-body non-invasive imaging along with the superior sensitivity and spatial resolution of surface-enhanced resonance Raman scattering (SERRS) imaging would allow both pre-operative mapping and intraoperative ... ...

Abstract	A single contrast agent that offers whole-body non-invasive imaging along with the superior sensitivity and spatial resolution of surface-enhanced resonance Raman scattering (SERRS) imaging would allow both pre-operative mapping and intraoperative imaging and thus be highly desirable. We hypothesized that labeling our recently reported ultrabright SERRS nanoparticles with a suitable radiotracer would enable pre-operative identification of regions of interest with whole body imaging that can be rapidly corroborated with a Raman imaging device or handheld Raman scanner in order to provide high precision guidance during surgical procedures. Here we present a straightforward new method that produces radiolabeled SERRS nanoparticles for combined positron emission tomography (PET)-SERRS tumor imaging without requiring the attachment of molecular chelators. We demonstrate the utility of these PET-SERRS nanoparticles in several proof-of-concept studies including lymph node (LN) tracking, intraoperative guidance for LN resection, and cancer imaging after intravenous injection. We anticipate that the radiolabeling method presented herein can be applied generally to nanoparticle substrates of various materials by first coating them with a silica shell and then applying the chelator-free protocol.
Language	English
Publishing date	2017
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2592097-2
ISSN	1838-7640 ; 1838-7640
ISSN (online)	1838-7640
ISSN	1838-7640
DOI	10.7150/thno.18019
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Detection of Marker-Free Precision Genome Editing and Genetic Variation through the Capture of Genomic Signatures.

Billon, Pierre / Nambiar, Tarun S / Hayward, Samuel B / Zafra, Maria P / Schatoff, Emma M / Oshima, Koichi / Dunbar, Andrew / Breinig, Marco / Park, Young C / Ryu, Han S / Tschaharganeh, Darjus F / Levine, Ross L / Baer, Richard / Ferrando, Adolfo / Dow, Lukas E / Ciccia, Alberto

Cell reports

2020 Volume 30, Issue 10, Page(s) 3280–3295.e6

Abstract: Genome editing technologies have transformed our ability to engineer desired genomic changes within living systems. However, detecting precise genomic modifications often requires sophisticated, expensive, and time-consuming experimental approaches. Here, ...

Abstract	Genome editing technologies have transformed our ability to engineer desired genomic changes within living systems. However, detecting precise genomic modifications often requires sophisticated, expensive, and time-consuming experimental approaches. Here, we describe DTECT (Dinucleotide signaTurE CapTure), a rapid and versatile detection method that relies on the capture of targeted dinucleotide signatures resulting from the digestion of genomic DNA amplicons by the type IIS restriction enzyme AcuI. DTECT enables the accurate quantification of marker-free precision genome editing events introduced by CRISPR-dependent homology-directed repair, base editing, or prime editing in various biological systems, such as mammalian cell lines, organoids, and tissues. Furthermore, DTECT allows the identification of oncogenic mutations in cancer mouse models, patient-derived xenografts, and human cancer patient samples. The ease, speed, and cost efficiency by which DTECT identifies genomic signatures should facilitate the generation of marker-free cellular and animal models of human disease and expedite the detection of human pathogenic variants.
MeSH term(s)	Animals ; BRCA1 Protein/genetics ; BRCA2 Protein/genetics ; Base Sequence ; DNA/genetics ; Disease Models, Animal ; Gene Editing ; Genetic Loci ; Genetic Markers ; Genetic Variation ; Genomics ; Genotype ; HEK293 Cells ; Humans ; Mice ; Mutation/genetics ; NIH 3T3 Cells ; Neoplasms/genetics ; Nucleotides/genetics ; Oncogenes ; Recombinational DNA Repair/genetics ; Restriction Mapping
Chemical Substances	BRCA1 Protein ; BRCA2 Protein ; Genetic Markers ; Nucleotides ; DNA (9007-49-2)
Language	English
Publishing date	2020-02-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2020.02.068
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