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  1. AU="Yun, Hwa Young"
  2. AU="C. Maridith Arthur"
  3. AU="Kunze, Ursula"
  4. AU="Adam Bienenstock"
  5. AU="Laviolette, M"
  6. AU="Mama, Khursheed R"
  7. AU="Sachse, Katharina" AU="Sachse, Katharina"
  8. AU="Skrlin, Branimir"
  9. AU="Mathais, Quentin"
  10. AU=Armstrong Ehrin J
  11. AU="Bahadi, Abdelaali"
  12. AU="Qin, Shuhui"
  13. AU="Huaraca-Quispe, Lidia P"
  14. AU=Petrovan Vlad AU=Petrovan Vlad AU=Petrovan Vlad
  15. AU="Elaina M Blair"
  16. AU="Hui Ram Kim"
  17. AU="Litvak, Yael"
  18. AU="Chen, Xiang-Yan"
  19. AU="Honorio Coronado, Eurídice N."
  20. AU="Garny, Hella"
  21. AU="Idris, Zamzuri"
  22. AU="Gao, Xinyu"
  23. AU="Tewari, Srishti"
  24. AU="Behrendt, Ulrike" AU="Behrendt, Ulrike"
  25. AU="Margenthaler, Julie A"
  26. AU="Si, Lian-Jing"
  27. AU="Strand, Torbjørn"
  28. AU=Abdoli Amir

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  1. Artikel ; Online: Annealing and purification of fluorescently labeled DNA substrates for in vitro assays.

    Tse, Ying Wah Elizabeth / Yun, Hwa Young / Wyatt, Haley Doris Myskiw

    STAR protocols

    2023  Band 4, Heft 1, Seite(n) 102128

    Abstract: We present a protocol to generate high-quality fluorescently labeled DNA substrates that can be used for biochemical assays, including DNA-binding and nuclease activity assays. We describe polyacrylamide-gel-electrophoresis-based purification of DNA ... ...

    Abstract We present a protocol to generate high-quality fluorescently labeled DNA substrates that can be used for biochemical assays, including DNA-binding and nuclease activity assays. We describe polyacrylamide-gel-electrophoresis-based purification of DNA oligonucleotides, followed by annealing the oligonucleotides and purifying the annealed substrates using anion-exchange chromatography. This protocol circumvents the use of radioisotopes, which require training and dedicated equipment for safe handling and necessitate specialized waste disposal. This protocol is amenable to varying lengths of oligonucleotides and DNA substrates. For complete details on the use and execution of this protocol, please refer to Payliss and Tse et al. (2022).
    Mesh-Begriff(e) DNA ; Oligonucleotides ; Biological Assay ; Electrophoresis, Polyacrylamide Gel
    Chemische Substanzen DNA (9007-49-2) ; Oligonucleotides
    Sprache Englisch
    Erscheinungsdatum 2023-02-20
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 2666-1667
    ISSN (online) 2666-1667
    DOI 10.1016/j.xpro.2023.102128
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: The in vivo Interaction Landscape of Histones H3.1 and H3.3.

    Siddaway, Robert / Milos, Scott / Coyaud, Étienne / Yun, Hwa Young / Morcos, Shahir M / Pajovic, Sanja / Campos, Eric I / Raught, Brian / Hawkins, Cynthia

    Molecular & cellular proteomics : MCP

    2022  Band 21, Heft 10, Seite(n) 100411

    Abstract: Chromatin structure, transcription, DNA replication, and repair are regulated via locus-specific incorporation of histone variants and posttranslational modifications that guide effector chromatin-binding proteins. Here we report unbiased, quantitative ... ...

    Abstract Chromatin structure, transcription, DNA replication, and repair are regulated via locus-specific incorporation of histone variants and posttranslational modifications that guide effector chromatin-binding proteins. Here we report unbiased, quantitative interactomes for the replication-coupled (H3.1) and replication-independent (H3.3) histone H3 variants based on BioID proximity labeling, which allows interactions in intact, living cells to be detected. Along with a significant proportion of previously reported interactions detected by affinity purification followed by mass spectrometry, three quarters of the 608 histone-associated proteins that we identified are new, uncharacterized histone associations. The data reveal important biological nuances not captured by traditional biochemical means. For example, we found that the chromatin assembly factor-1 histone chaperone not only deposits the replication-coupled H3.1 histone variant during S-phase but also associates with H3.3 throughout the cell cycle in vivo. We also identified other variant-specific associations, such as with transcription factors, chromatin regulators, and with the mitotic machinery. Our proximity-based analysis is thus a rich resource that extends the H3 interactome and reveals new sets of variant-specific associations.
    Mesh-Begriff(e) Histones/metabolism ; Histone Chaperones/genetics ; Histone Chaperones/metabolism ; Chromatin ; Chromatin Assembly Factor-1/genetics ; Chromatin Assembly Factor-1/metabolism ; Transcription Factors/metabolism ; Nucleosomes
    Chemische Substanzen Histones ; Histone Chaperones ; Chromatin ; Chromatin Assembly Factor-1 ; Transcription Factors ; Nucleosomes
    Sprache Englisch
    Erscheinungsdatum 2022-09-09
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 2075924-1
    ISSN 1535-9484 ; 1535-9476
    ISSN (online) 1535-9484
    ISSN 1535-9476
    DOI 10.1016/j.mcpro.2022.100411
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5599: Hefte anzeigen Standort:
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  3. Artikel ; Online: Phosphorylation of the DNA repair scaffold SLX4 drives folding of the SAP domain and activation of the MUS81-EME1 endonuclease.

    Payliss, Brandon J / Tse, Ying Wah E / Reichheld, Sean E / Lemak, Alexander / Yun, Hwa Young / Houliston, Scott / Patel, Ayushi / Arrowsmith, Cheryl H / Sharpe, Simon / Wyatt, Haley D M

    Cell reports

    2022  Band 41, Heft 4, Seite(n) 111537

    Abstract: The DNA repair scaffold SLX4 has multifaceted roles in genome stability, many of which depend on structure-selective endonucleases. SLX4 coordinates the cell cycle-regulated assembly of SLX1, MUS81-EME1, and XPF-ERCC1 into a tri-nuclease complex called ... ...

    Abstract The DNA repair scaffold SLX4 has multifaceted roles in genome stability, many of which depend on structure-selective endonucleases. SLX4 coordinates the cell cycle-regulated assembly of SLX1, MUS81-EME1, and XPF-ERCC1 into a tri-nuclease complex called SMX. Mechanistically, how the mitotic kinase CDK1 regulates the interaction between SLX4 and MUS81-EME1 remains unclear. Here, we show that CDK1-cyclin B phosphorylates SLX4 residues T1544, T1561, and T1571 in the MUS81-binding region (SLX4
    Mesh-Begriff(e) Endonucleases/metabolism ; Phosphorylation ; Recombinases/metabolism ; DNA-Binding Proteins/metabolism ; DNA Repair ; Cyclin B/metabolism ; Endodeoxyribonucleases/metabolism
    Chemische Substanzen Endonucleases (EC 3.1.-) ; Recombinases ; DNA-Binding Proteins ; Cyclin B ; Endodeoxyribonucleases (EC 3.1.-)
    Sprache Englisch
    Erscheinungsdatum 2022-10-26
    Erscheinungsland United States
    Dokumenttyp Journal Article ; 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.2022.111537
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Oncohistone interactome profiling uncovers contrasting oncogenic mechanisms and identifies potential therapeutic targets in high grade glioma.

    Siddaway, Robert / Canty, Laura / Pajovic, Sanja / Milos, Scott / Coyaud, Etienne / Sbergio, Stefanie-Grace / Vadivel Anguraj, Arun Kumaran / Lubanszky, Evan / Yun, Hwa Young / Portante, Alessia / Carette, Sheyenne / Zhang, Cunjie / Moran, Michael F / Raught, Brian / Campos, Eric I / Hawkins, Cynthia

    Acta neuropathologica

    2022  Band 144, Heft 5, Seite(n) 1027–1048

    Abstract: Histone H3 mutations at amino acids 27 (H3K27M) and 34 (H3G34R) are recurrent drivers of pediatric-type high-grade glioma (pHGG). H3K27M mutations lead to global disruption of H3K27me3 through dominant negative PRC2 inhibition, while H3G34R mutations ... ...

    Abstract Histone H3 mutations at amino acids 27 (H3K27M) and 34 (H3G34R) are recurrent drivers of pediatric-type high-grade glioma (pHGG). H3K27M mutations lead to global disruption of H3K27me3 through dominant negative PRC2 inhibition, while H3G34R mutations lead to local losses of H3K36me3 through inhibition of SETD2. However, their broader oncogenic mechanisms remain unclear. We characterized the H3.1K27M, H3.3K27M and H3.3G34R interactomes, finding that H3K27M is associated with epigenetic and transcription factor changes; in contrast H3G34R removes a break on cryptic transcription, limits DNA methyltransferase access, and alters mitochondrial metabolism. All 3 mutants had altered interactions with DNA repair proteins and H3K9 methyltransferases. H3K9me3 was reduced in H3K27M-containing nucleosomes, and cis-H3K9 methylation was required for H3K27M to exert its effect on global H3K27me3. H3K9 methyltransferase inhibition was lethal to H3.1K27M, H3.3K27M and H3.3G34R pHGG cells, underscoring the importance of H3K9 methylation for oncohistone-mutant gliomas and suggesting it as an attractive therapeutic target.
    Mesh-Begriff(e) Amino Acids/genetics ; Child ; DNA ; Glioma/genetics ; Glioma/metabolism ; Histones/genetics ; Humans ; Mutation/genetics ; Nucleosomes ; Transcription Factors/genetics
    Chemische Substanzen Amino Acids ; Histones ; Nucleosomes ; Transcription Factors ; DNA (9007-49-2)
    Sprache Englisch
    Erscheinungsdatum 2022-09-07
    Erscheinungsland Germany
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1079-0
    ISSN 1432-0533 ; 0001-6322
    ISSN (online) 1432-0533
    ISSN 0001-6322
    DOI 10.1007/s00401-022-02489-2
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Noncoding mutations target cis-regulatory elements of the FOXA1 plexus in prostate cancer.

    Zhou, Stanley / Hawley, James R / Soares, Fraser / Grillo, Giacomo / Teng, Mona / Madani Tonekaboni, Seyed Ali / Hua, Junjie Tony / Kron, Ken J / Mazrooei, Parisa / Ahmed, Musaddeque / Arlidge, Christopher / Yun, Hwa Young / Livingstone, Julie / Huang, Vincent / Yamaguchi, Takafumi N / Espiritu, Shadrielle M G / Zhu, Yanyun / Severson, Tesa M / Murison, Alex /
    Cameron, Sarina / Zwart, Wilbert / van der Kwast, Theodorus / Pugh, Trevor J / Fraser, Michael / Boutros, Paul C / Bristow, Robert G / He, Housheng Hansen / Lupien, Mathieu

    Nature communications

    2020  Band 11, Heft 1, Seite(n) 441

    Abstract: Prostate cancer is the second most commonly diagnosed malignancy among men worldwide. Recurrently mutated in primary and metastatic prostate tumors, FOXA1 encodes a pioneer transcription factor involved in disease onset and progression through both ... ...

    Abstract Prostate cancer is the second most commonly diagnosed malignancy among men worldwide. Recurrently mutated in primary and metastatic prostate tumors, FOXA1 encodes a pioneer transcription factor involved in disease onset and progression through both androgen receptor-dependent and androgen receptor-independent mechanisms. Despite its oncogenic properties however, the regulation of FOXA1 expression remains unknown. Here, we identify a set of six cis-regulatory elements in the FOXA1 regulatory plexus harboring somatic single-nucleotide variants in primary prostate tumors. We find that deletion and repression of these cis-regulatory elements significantly decreases FOXA1 expression and prostate cancer cell growth. Six of the ten single-nucleotide variants mapping to FOXA1 regulatory plexus significantly alter the transactivation potential of cis-regulatory elements by modulating the binding of transcription factors. Collectively, our results identify cis-regulatory elements within the FOXA1 plexus mutated in primary prostate tumors as potential targets for therapeutic intervention.
    Mesh-Begriff(e) Binding Sites ; Cell Line, Tumor ; Cell Proliferation/genetics ; Gene Expression Regulation, Neoplastic ; Hepatocyte Nuclear Factor 3-alpha/genetics ; Humans ; Male ; Mutation ; Prostatic Neoplasms/genetics ; Regulatory Sequences, Nucleic Acid ; Transcription Factors/metabolism
    Chemische Substanzen FOXA1 protein, human ; Hepatocyte Nuclear Factor 3-alpha ; Transcription Factors
    Sprache Englisch
    Erscheinungsdatum 2020-01-23
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-020-14318-9
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Versatile strategy for controlling the specificity and activity of engineered T cells.

    Ma, Jennifer S Y / Kim, Ji Young / Kazane, Stephanie A / Choi, Sei-Hyun / Yun, Hwa Young / Kim, Min Soo / Rodgers, David T / Pugh, Holly M / Singer, Oded / Sun, Sophie B / Fonslow, Bryan R / Kochenderfer, James N / Wright, Timothy M / Schultz, Peter G / Young, Travis S / Kim, Chan Hyuk / Cao, Yu

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

    2016  Band 113, Heft 4, Seite(n) E450–8

    Abstract: The adoptive transfer of autologous T cells engineered to express a chimeric antigen receptor (CAR) has emerged as a promising cancer therapy. Despite impressive clinical efficacy, the general application of current CAR-T--cell therapy is limited by ... ...

    Abstract The adoptive transfer of autologous T cells engineered to express a chimeric antigen receptor (CAR) has emerged as a promising cancer therapy. Despite impressive clinical efficacy, the general application of current CAR-T--cell therapy is limited by serious treatment-related toxicities. One approach to improve the safety of CAR-T cells involves making their activation and proliferation dependent upon adaptor molecules that mediate formation of the immunological synapse between the target cancer cell and T-cell. Here, we describe the design and synthesis of structurally defined semisynthetic adaptors we refer to as "switch" molecules, in which anti-CD19 and anti-CD22 antibody fragments are site-specifically modified with FITC using genetically encoded noncanonical amino acids. This approach allows the precise control over the geometry and stoichiometry of complex formation between CD19- or CD22-expressing cancer cells and a "universal" anti-FITC-directed CAR-T cell. Optimization of this CAR-switch combination results in potent, dose-dependent in vivo antitumor activity in xenograft models. The advantage of being able to titrate CAR-T-cell in vivo activity was further evidenced by reduced in vivo toxicity and the elimination of persistent B-cell aplasia in immune-competent mice. The ability to control CAR-T cell and cancer cell interactions using intermediate switch molecules may expand the scope of engineered T-cell therapy to solid tumors, as well as indications beyond cancer therapy.
    Mesh-Begriff(e) Animals ; Antigens, CD19/immunology ; Antigens, Neoplasm/immunology ; Azides ; B-Lymphocytes/immunology ; B-Lymphocytes/pathology ; Cell Line, Tumor ; Cytotoxicity, Immunologic ; Female ; Fluorescein-5-isothiocyanate ; Genetic Vectors ; Humans ; Immunotherapy, Adoptive/adverse effects ; Immunotherapy, Adoptive/methods ; Lentivirus/genetics ; Leukemia, B-Cell/therapy ; Lymphocyte Activation ; Lymphopenia/etiology ; Lymphopenia/prevention & control ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, SCID ; Models, Molecular ; Phenylalanine/analogs & derivatives ; Protein Conformation ; Protein Engineering/methods ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/immunology ; Recombinant Fusion Proteins/immunology ; Sialic Acid Binding Ig-like Lectin 2/immunology ; Single-Chain Antibodies/genetics ; Single-Chain Antibodies/immunology ; T-Cell Antigen Receptor Specificity ; T-Lymphocytes/immunology ; T-Lymphocytes/transplantation ; Transduction, Genetic ; Xenograft Model Antitumor Assays
    Chemische Substanzen Antigens, CD19 ; Antigens, Neoplasm ; Azides ; CD22 protein, human ; CTL019 chimeric antigen receptor ; Receptors, Antigen, T-Cell ; Recombinant Fusion Proteins ; Sialic Acid Binding Ig-like Lectin 2 ; Single-Chain Antibodies ; 4-azidophenylalanine (33173-53-4) ; Phenylalanine (47E5O17Y3R) ; Fluorescein-5-isothiocyanate (I223NX31W9)
    Sprache Englisch
    Erscheinungsdatum 2016-01-12
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.1524193113
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1148: Hefte anzeigen Standort:
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  7. Artikel ; Online: Design of Switchable Chimeric Antigen Receptor T Cells Targeting Breast Cancer.

    Cao, Yu / Rodgers, David T / Du, Juanjuan / Ahmad, Insha / Hampton, Eric N / Ma, Jennifer S Y / Mazagova, Magdalena / Choi, Sei-Hyun / Yun, Hwa Young / Xiao, Han / Yang, Pengyu / Luo, Xiaozhou / Lim, Reyna K V / Pugh, Holly M / Wang, Feng / Kazane, Stephanie A / Wright, Timothy M / Kim, Chan Hyuk / Schultz, Peter G /
    Young, Travis S

    Angewandte Chemie (International ed. in English)

    2016  Band 55, Heft 26, Seite(n) 7520–7524

    Abstract: Chimeric antigen receptor T (CAR-T) cells have demonstrated promising results against hematological malignancies, but have encountered significant challenges in translation to solid tumors. To overcome these hurdles, we have developed a switchable CAR-T ... ...

    Abstract Chimeric antigen receptor T (CAR-T) cells have demonstrated promising results against hematological malignancies, but have encountered significant challenges in translation to solid tumors. To overcome these hurdles, we have developed a switchable CAR-T cell platform in which the activity of the engineered cell is controlled by dosage of an antibody-based switch. Herein, we apply this approach to Her2-expressing breast cancers by engineering switch molecules through site-specific incorporation of FITC or grafting of a peptide neo-epitope (PNE) into the anti-Her2 antibody trastuzumab (clone 4D5). We demonstrate that both switch formats can be readily optimized to redirect CAR-T cells (specific for the corresponding FITC or PNE) to Her2-expressing tumor cells, and afford dose-titratable activation of CAR-T cells ex vivo and complete clearance of the tumor in rodent xenograft models. This strategy may facilitate the application of immunotherapy to solid tumors by affording comparable efficacy with improved safety owing to switch-based control of the CAR-T response.
    Mesh-Begriff(e) Animals ; Breast Neoplasms/therapy ; Dose-Response Relationship, Drug ; Female ; Genes, Switch/genetics ; Heterografts ; Humans ; Immunotherapy ; Mice ; Receptor, ErbB-2/drug effects ; Receptor, ErbB-2/metabolism ; Receptors, Antigen, T-Cell
    Chemische Substanzen Receptors, Antigen, T-Cell ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1)
    Sprache Englisch
    Erscheinungsdatum 2016-05-04
    Erscheinungsland Germany
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2011836-3
    ISSN 1521-3773 ; 1433-7851
    ISSN (online) 1521-3773
    ISSN 1433-7851
    DOI 10.1002/anie.201601902
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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