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Your search keyword '"Dröge, Peter"' showing total 325 results
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325 results on '"Dröge, Peter"'

1. Peer-Review Statements

Author

Droege, Peter, Quint, Lelia, Zheng, Zheng, Editor-in-Chief, Xi, Zhiyu, Associate Editor, Gong, Siqian, Series Editor, Hong, Wei-Chiang, Series Editor, Mellal, Mohamed Arezki, Series Editor, Narayanan, Ramadas, Series Editor, Nguyen, Quang Ngoc, Series Editor, Ong, Hwai Chyuan, Series Editor, Sun, Zaicheng, Series Editor, Ullah, Sharif, Series Editor, Wu, Junwei, Series Editor, Zhang, Baochang, Series Editor, Zhang, Wei, Series Editor, Zhu, Quanxin, Series Editor, Zheng, Wei, Series Editor, Droege, Peter, editor, and Quint, Lelia, editor

Published
2024
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2. Signalling inhibition by ponatinib disrupts productive alternative lengthening of telomeres (ALT)

Author

Kusuma, Frances Karla, Prabhu, Aishvaryaa, Tieo, Galen, Ahmed, Syed Moiz, Dakle, Pushkar, Yong, Wai Khang, Pathak, Elina, Madan, Vikas, Jiang, Yan Yi, Tam, Wai Leong, Kappei, Dennis, Dröge, Peter, Koeffler, H Phillip, and Jeitany, Maya

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Orphan Drug, Rare Diseases, Cancer, Genetics, Aetiology, 5.1 Pharmaceuticals, 2.1 Biological and endogenous factors, Development of treatments and therapeutic interventions, Telomere, Cell Survival, Signal Transduction, Gene Expression Regulation, DNA Repair, DNA Replication, JNK Mitogen-Activated Protein Kinases, Humans, Animals, Mice, Cell Line, Tumor
Abstract

Alternative lengthening of telomeres (ALT) supports telomere maintenance in 10-15% of cancers, thus representing a compelling target for therapy. By performing anti-cancer compound library screen on isogenic cell lines and using extrachromosomal telomeric C-circles, as a bona fide marker of ALT activity, we identify a receptor tyrosine kinase inhibitor ponatinib that deregulates ALT mechanisms, induces telomeric dysfunction, reduced ALT-associated telomere synthesis, and targets, in vivo, ALT-positive cells. Using RNA-sequencing and quantitative phosphoproteomic analyses, combined with C-circle level assessment, we find an ABL1-JNK-JUN signalling circuit to be inhibited by ponatinib and to have a role in suppressing telomeric C-circles. Furthermore, transcriptome and interactome analyses suggest a role of JUN in DNA damage repair. These results are corroborated by synergistic drug interactions between ponatinib and either DNA synthesis or repair inhibitors, such as triciribine. Taken together, we describe here a signalling pathway impacting ALT which can be targeted by a clinically approved drug.

Published
2023

4. Peer-Review Statements

Author

Schossig, Peter, Droege, Peter, Riemer, Antonia, Speer, Martin, Zheng, Zheng, Editor-in-Chief, Xi, Zhiyu, Associate Editor, Gong, Siqian, Series Editor, Hong, Wei-Chiang, Series Editor, Mellal, Mohamed Arezki, Series Editor, Narayanan, Ramadas, Series Editor, Nguyen, Quang Ngoc, Series Editor, Ong, Hwai Chyuan, Series Editor, Sun, Zaicheng, Series Editor, Ullah, Sharif, Series Editor, Wu, Junwei, Series Editor, Zhang, Baochang, Series Editor, Zhang, Wei, Series Editor, Zhu, Quanxin, Series Editor, Zheng, Wei, Series Editor, Schossig, Peter, editor, Droege, Peter, editor, Riemer, Antonia, editor, and Speer, Martin, editor

Published
2023
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5. Abstract LT07: Signalling Inhibition by Ponatinib Disrupts Productive Alternative Lengthening of Telomeres (ALT)

Author

Kusuma, Frances, primary, Prabhu, Aishvaryaa, additional, Tieo, Galen, additional, Ahmad, Syed Moiz, additional, Dakle, Pushkar, additional, Yong, Wai Khang, additional, Pathak, Elina, additional, Madan, Vikas, additional, Jiang, Yan Yi, additional, Tam, Wai Leong, additional, Kappei, Dennis, additional, Dröge, Peter, additional, Koeffler, H. Phillip, additional, and Jeitany, Maya, additional

Published
2024
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11. A versatile genomic transgenesis platform with enhanced λ integrase for human Expi293F cells

Author

Siddiqui, Asim Azhar, Peter, Sabrina, Ngoh, Eve Zi Xian, Wang, Cheng-I, Ng, Shirelle, Dangerfield, John A., Gunzburg, Walter H., Dröge, Peter, Makhija, Harshyaa, School of Biological Sciences, and Singapore Immunology Network, A*STAR

Subjects
Human Cell Line Engineering, Biotherapeutics, Site-Specific Transgenesis, Science, λ Integrase, Expi293F Cells, Microencapsulation
Abstract

Reliable cell-based platforms to test and/or produce biologics in a sustainable manner are important for the biotech industry. Utilizing enhanced λ integrase, a sequence-specific DNA recombinase, we developed a novel transgenesis platform involving a fully characterized single genomic locus as an artificial landing pad for transgene insertion in human Expi293F cells. Importantly, transgene instability and variation in expression were not observed in the absence of selection pressure, thus enabling reliable long-term biotherapeutics testing or production. The artificial landing pad for λ integrase can be targeted with multi-transgene constructs and offers future modularity involving additional genome manipulation tools to generate sequential or nearly seamless insertions. We demonstrated broad utility with expression constructs for anti PD-1 monoclonal antibodies and showed that the orientation of heavy and light chain transcription units profoundly affected antibody expression levels. In addition, we demonstrated encapsulation of our PD-1 platform cells into bio-compatible mini-bioreactors and the continued secretion of antibodies, thus providing a basis for future cell-based 32 applications for more effective and affordable therapies. Agency for Science, Technology and Research (A*STAR) National Research Foundation (NRF) Published version This work was supported through a grant from the National Research Foundation-Competitive Research Programme, Singapore to P.D. (NRF-CRP21-2018-0002), and the Core Fund from the Singapore Immunology Network, Agency for Science, Technology and Research, Singapore to C-I.W.

Published
2023

12. The FGFR inhibitor PD173074 binds to the C‐terminus of oncofetal HMGA2 and modulates its DNA‐binding and transcriptional activation functions.

Author

Ahmed, Syed Moiz, Ragunathan, Priya, Shin, Joon, Peter, Sabrina, Kleissle, Sabrina, Neuenschwander, Martin, Schäfer, Reinhold, Kries, Jens Peter V., Grüber, Gerhard, and Dröge, Peter

Subjects
FIBROBLAST growth factor receptors, GENETIC regulation, CHEMICAL libraries, REPORTER genes, SOMATIC cells
Abstract

The architectural chromatin factor high‐mobility group AT‐hook 2 (HMGA2) is causally involved in several human malignancies and pathologies. HMGA2 is not expressed in most normal adult somatic cells, which renders the protein an attractive drug target. An established cell‐based compound library screen identified the fibroblast growth factor receptor (FGFR) inhibitor PD173074 as an antagonist of HMGA2‐mediated transcriptional reporter gene activation. We determined that PD173074 binds the C‐terminus of HMGA2 and interferes with functional coordination of the three AT‐hook DNA‐binding domains mediated by the C‐terminus. The HMGA2‐antagonistic effect of PD173074 on transcriptional activation may therefore result from an induced altered DNA‐binding mode of HMGA2. PD173074 as a novel HMGA2‐specific antagonist could trigger the development of derivates with enhanced attributes and clinical potential. [ABSTRACT FROM AUTHOR]

Published
2023
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35. Discovery of a Novel Mycobacterial F‐ATP Synthase Inhibitor and its Potency in Combination with Diarylquinolines

Author

Hotra, Adam, primary, Ragunathan, Priya, additional, Ng, Pearly Shuyi, additional, Seankongsuk, Pattarakiat, additional, Harikishore, Amaravadhi, additional, Sarathy, Jickky Palmae, additional, Saw, Wuan‐Geok, additional, Lakshmanan, Umayal, additional, Sae‐Lao, Patcharaporn, additional, Kalia, Nitin Pal, additional, Shin, Joon, additional, Kalyanasundaram, Revathy, additional, Anbarasu, Sivaraj, additional, Parthasarathy, Krupakar, additional, Pradeep, Chaudhari Namrata, additional, Makhija, Harshyaa, additional, Dröge, Peter, additional, Poulsen, Anders, additional, Tan, Jocelyn Hui Ling, additional, Pethe, Kevin, additional, Dick, Thomas, additional, Bates, Roderick W., additional, and Grüber, Gerhard, additional

Published
2020
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42. The chromatin structuring protein HMGA2 influences human subtelomere stability and cancer chemosensitivity

Author

Ahmed, Syed Moiz, primary, Ramani, Priya Dharshana, additional, Wong, Stephen Qi Rong, additional, Zhao, Xiaodan, additional, Ivanyi-Nagy, Roland, additional, Leong, Tang Choong, additional, Chua, Clarinda, additional, Li, Zhizhong, additional, Hentze, Hannes, additional, Tan, Iain BeeHuat, additional, Yan, Jie, additional, DasGupta, Ramanuj, additional, and Dröge, Peter, additional

Published
2019
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