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Targeting oxidative repair proteins for treatment of cancer and inflammation

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Publications

Targeting OGG1 arrests cancer cell proliferation by inducing replication stress

Author(s): Torkild Visnes, Carlos Benítez-Buelga, Armando Cázares-Körner, Kumar Sanjiv, Bishoy M F Hanna, Oliver Mortusewicz, Varshni Rajagopal, Julian J Albers, Daniel W Hagey, Tove Bekkhus, Saeed Eshtad, Juan Miguel Baquero, Geoffrey Masuyer, Olov Wallner, Sarah Müller, Therese Pham, Camilla Göktürk, Azita Rasti, Sharda Suman, Raúl Torres-Ruiz, Antonio Sarno, Elisée Wiita, Evert J Homan, Stella Kar
Published in: Nucleic Acids Research, 48/21, 2020, Page(s) 12234-12251, ISSN 0305-1048
Publisher: Oxford University Press
DOI: 10.1093/nar/gkaa1048

Crystal structures of human PAICS reveal substrate and product binding of an emerging cancer target

Author(s): Jana Škerlová, Judith Unterlass, Mona Göttmann, Petra Marttila, Evert Homan, Thomas Helleday, Ann-Sofie Jemth, Pål Stenmark
Published in: Journal of Biological Chemistry, 295/33, 2020, Page(s) 11656-11668, ISSN 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology Inc.
DOI: 10.1074/jbc.ra120.013695

Targeting PFKFB3 radiosensitizes cancer cells and suppresses homologous recombination

Author(s): Nina M. S. Gustafsson, Katarina Färnegårdh, Nadilly Bonagas, Anna Huguet Ninou, Petra Groth, Elisee Wiita, Mattias Jönsson, Kenth Hallberg, Jemina Lehto, Rosa Pennisi, Jessica Martinsson, Carina Norström, Jessica Hollers, Johan Schultz, Martin Andersson, Natalia Markova, Petra Marttila, Baek Kim, Martin Norin, Thomas Olin, Thomas Helleday
Published in: Nature Communications, 9/1, 2018, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-018-06287-x

MTH1 Inhibitor TH588 Disturbs Mitotic Progression and Induces Mitosis-Dependent Accumulation of Genomic 8-oxodG

Author(s): Sean G. Rudd, Helge Gad, Kumar Sanjiv, Nuno Amaral, Anna Hagenkort, Petra Groth, Cecilia E. Ström, Oliver Mortusewicz, Ulrika Warpman Berglund, Thomas Helleday
Published in: Cancer Research, 80/17, 2020, Page(s) 3530-3541, ISSN 0008-5472
Publisher: American Association for Cancer Research
DOI: 10.1158/0008-5472.can-19-0883

Author Correction: Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells

Author(s): Brent D. G. Page, Nicholas C. K. Valerie, Roni H. G. Wright, Olov Wallner, Rebecka Isaksson, Megan Carter, Sean G. Rudd, Olga Loseva, Ann-Sofie Jemth, Ingrid Almlöf, Jofre Font-Mateu, Sabin Llona-Minguez, Pawel Baranczewski, Fredrik Jeppsson, Evert Homan, Helena Almqvist, Hanna Axelsson, Shruti Regmi, Anna-Lena Gustavsson, Thomas Lundbäck, Martin Scobie, Kia Strömberg, Pål Stenmark, Miguel Bea
Published in: Nature Communications, 10/1, 2019, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-019-12806-1

MetaCNV - a consensus approach to infer accurate copy numbers from low coverage data

Author(s): Stefanie Friedrich, Remus Barbulescu, Thomas Helleday, Erik L. L. Sonnhammer
Published in: BMC Medical Genomics, 13/1, 2020, ISSN 1755-8794
Publisher: BioMed Central
DOI: 10.1186/s12920-020-00731-y

The MTH1 inhibitor TH588 is a microtubule-modulating agent that eliminates cancer cells by activating the mitotic surveillance pathway

Author(s): Nadia Gul, Joakim Karlsson, Carolina Tängemo, Sanna Linsefors, Samuel Tuyizere, Rosie Perkins, Chandu Ala, Zhiyuan Zou, Erik Larsson, Martin O. Bergö, Per Lindahl
Published in: Scientific Reports, 9/1, 2019, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-019-51205-w

Karonudib has potent anti-tumor effects in preclinical models of B-cell lymphoma

Author(s): Morten P. Oksvold, Ulrika Warpman Berglund, Helge Gad, Baoyan Bai, Trond Stokke, Idun Dale Rein, Therese Pham, Kumar Sanjiv, Geir Frode Øy, Jens Henrik Norum, Erlend B. Smeland, June H. Myklebust, Thomas Helleday, Thea Kristin Våtsveen
Published in: Scientific Reports, 11/1, 2021, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-021-85613-8

MutT homologue 1 (MTH1) removes N6-methyl-dATP from the dNTP pool

Author(s): Emma Rose Scaletti, Karl S. Vallin, Lars Bräutigam, Antonio Sarno, Ulrika Warpman Berglund, Thomas Helleday, Pål Stenmark, Ann-Sofie Jemth
Published in: Journal of Biological Chemistry, 295/15, 2020, Page(s) 4761-4772, ISSN 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology Inc.
DOI: 10.1074/jbc.ra120.012636

NUDT15-mediated hydrolysis limits the efficacy of anti-HCMV drug ganciclovir

Author(s): Si Min Zhang, Daniel Rehling, Ann-Sofie Jemth, Adam Throup, Natalia Landázuri, Ingrid Almlöf, Mona Göttmann, Nicholas C.K. Valerie, Sanjay R. Borhade, Prasad Wakchaure, Brent D.G. Page, Matthieu Desroses, Evert J. Homan, Martin Scobie, Sean G. Rudd, Ulrika Warpman Berglund, Cecilia Söderberg-Nauclér, Pål Stenmark, Thomas Helleday
Published in: Cell Chemical Biology, 2021, ISSN 2451-9456
Publisher: Elsevier BV
DOI: 10.1016/j.chembiol.2021.06.001

Ribonucleotide reductase inhibitors suppress SAMHD 1 ara‐ CTP ase activity enhancing cytarabine efficacy

Author(s): Sean G Rudd, Nikolaos Tsesmetzis, Kumar Sanjiv, Cynthia BJ Paulin, Lakshmi Sandhow, Juliane Kutzner, Ida Hed Myrberg, Sarah S Bunten, Hanna Axelsson, Si Min Zhang, Azita Rasti, Petri Mäkelä, Si'Ana A Coggins, Sijia Tao, Sharda Suman, Rui M Branca, Georgios Mermelekas, Elisée Wiita, Sun Lee, Julian Walfridsson, Raymond F Schinazi, Baek Kim, Janne Lehtiö, Georgios Z Rassidakis, Katja Pokrovskaja
Published in: EMBO Molecular Medicine, 12/3, 2020, ISSN 1757-4676
Publisher: John Wiley & Sons Ltd.
DOI: 10.15252/emmm.201910419

NEIL3 Prevents Senescence in Hepatocellular Carcinoma by Repairing Oxidative Lesions at Telomeres during Mitosis

Author(s): Zhenjun Zhao, Helge Gad, Carlos Benitez-Buelga, Kumar Sanjiv, Hua Xiangwei, He Kang, Mingxuan Feng, Zhicong Zhao, Ulrika Warpman Berglund, Qiang Xia, Thomas Helleday
Published in: Cancer Research, 81/15, 2021, Page(s) 4079-4093, ISSN 0008-5472
Publisher: American Association for Cancer Research
DOI: 10.1158/0008-5472.can-20-1028

Small molecule inhibitor of OGG1 blocks oxidative DNA damage repair at telomeres and potentiates methotrexate anticancer effects

Author(s): Juan Miguel Baquero, Carlos Benítez-Buelga, Varshni Rajagopal, Zhao Zhenjun, Raúl Torres-Ruiz, Sarah Müller, Bishoy M. F. Hanna, Olga Loseva, Olov Wallner, Maurice Michel, Sandra Rodríguez-Perales, Helge Gad, Torkild Visnes, Thomas Helleday, Javier Benítez, Ana Osorio
Published in: Scientific Reports, 11/1, 2021, ISSN 2045-2322
Publisher: Nature Publishing Group
DOI: 10.1038/s41598-021-82917-7

Distinct mechanistic responses to replication fork stalling induced by either nucleotide or protein deprivation

Author(s): Sofia Henriksson, Petra Groth, Nina Gustafsson, Thomas Helleday
Published in: Cell Cycle, 17/5, 2018, Page(s) 568-579, ISSN 1538-4101
Publisher: Landes Bioscience
DOI: 10.1080/15384101.2017.1387696

Crystal structures of NUDT15 variants enabled by a potent inhibitor reveal the structural basis for thiopurine sensitivity

Author(s): Daniel Rehling, Si Min Zhang, Ann-Sofie Jemth, Tobias Koolmeister, Adam Throup, Olov Wallner, Emma Scaletti, Takaya Moriyama, Rina Nishii, Jonathan Davies, Matthieu Desroses, Sean G. Rudd, Martin Scobie, Evert Homan, Ulrika Warpman Berglund, Jun J. Yang, Thomas Helleday, Pål Stenmark
Published in: Journal of Biological Chemistry, 296, 2021, Page(s) 100568, ISSN 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology Inc.
DOI: 10.1016/j.jbc.2021.100568

In silico Druggability Assessment of the NUDIX Hydrolase Protein Family as a Workflow for Target Prioritization

Author(s): Maurice Michel, Evert J. Homan, Elisée Wiita, Kia Pedersen, Ingrid Almlöf, Anna-Lena Gustavsson, Thomas Lundbäck, Thomas Helleday, Ulrika Warpman Berglund
Published in: Frontiers in Chemistry, 8, 2020, ISSN 2296-2646
Publisher: Frontiers in Chemistry
DOI: 10.3389/fchem.2020.00443

The antimalarial drug amodiaquine stabilizes p53 through ribosome biogenesis stress, independently of its autophagy-inhibitory activity

Author(s): Jaime A. Espinoza, Asimina Zisi, Dimitris C. Kanellis, Jordi Carreras-Puigvert, Martin Henriksson, Daniela Hühn, Kenji Watanabe, Thomas Helleday, Mikael S. Lindström, Jiri Bartek
Published in: Cell Death & Differentiation, 27/2, 2020, Page(s) 773-789, ISSN 1350-9047
Publisher: Nature Publishing Group
DOI: 10.1038/s41418-019-0387-5

Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation

Author(s): Torkild Visnes, Armando Cázares-Körner, Wenjing Hao, Olov Wallner, Geoffrey Masuyer, Olga Loseva, Oliver Mortusewicz, Elisée Wiita, Antonio Sarno, Aleksandr Manoilov, Juan Astorga-Wells, Ann-Sofie Jemth, Lang Pan, Kumar Sanjiv, Stella Karsten, Camilla Gokturk, Maurice Grube, Evert J. Homan, Bishoy M. F. Hanna, Cynthia B. J. Paulin, Therese Pham, Azita Rasti, Ulrika Warpman Berglund, Catharina v
Published in: Science, 362/6416, 2018, Page(s) 834-839, ISSN 0036-8075
Publisher: American Association for the Advancement of Science
DOI: 10.1126/science.aar8048

MutT homologue 1 (MTH1) catalyzes the hydrolysis of mutagenic O6-methyl-dGTP

Author(s): Ann-Sofie Jemth, Robert Gustafsson, Lars Bräutigam, Linda Henriksson, Karl S A Vallin, Antonio Sarno, Ingrid Almlöf, Evert Homan, Azita Rasti, Ulrika Warpman Berglund, Pål Stenmark, Thomas Helleday
Published in: Nucleic Acids Research, 2018, ISSN 0305-1048
Publisher: Oxford University Press
DOI: 10.1093/nar/gky896

A comprehensive structural, biochemical and biological profiling of the human NUDIX hydrolase family

Author(s): Jordi Carreras-Puigvert, Marinka Zitnik, Ann-Sofie Jemth, Megan Carter, Judith E. Unterlass, Björn Hallström, Olga Loseva, Zhir Karem, José Manuel Calderón-Montaño, Cecilia Lindskog, Per-Henrik Edqvist, Damian J. Matuszewski, Hammou Ait Blal, Ronnie P. A. Berntsson, Maria Häggblad, Ulf Martens, Matthew Studham, Bo Lundgren, Carolina Wählby, Erik L. L. Sonnhammer, Emma Lundberg, Pål Stenmar
Published in: Nature Communications, 8/1, 2017, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-017-01642-w

Targeted NUDT5 inhibitors block hormone signaling in breast cancer cells

Author(s): Brent D. G. Page, Nicholas C. K. Valerie, Roni H. G. Wright, Olov Wallner, Rebecka Isaksson, Megan Carter, Sean G. Rudd, Olga Loseva, Ann-Sofie Jemth, Ingrid Almlöf, Jofre Font-Mateu, Sabin Llona-Minguez, Pawel Baranczewski, Fredrik Jeppsson, Evert Homan, Helena Almqvist, Hanna Axelsson, Shruti Regmi, Anna-Lena Gustavsson, Thomas Lundbäck, Martin Scobie, Kia Strömberg, Pål Stenmark, Miguel Bea
Published in: Nature Communications, 9/1, 2018, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/s41467-017-02293-7

Glioblastoma and glioblastoma stem cells are dependent on functional MTH1

Author(s): Linda Pudelko, Pegah Rouhi, Kumar Sanjiv, Helge Gad, Christina Kalderén, Andreas Höglund, Massimo Squatrito, Alberto J. Schuhmacher, Steven Edwards, Daniel Hägerstrand, Ulrika Warpman Berglund, Thomas Helleday, Lars Bräutigam
Published in: Oncotarget, 8/49, 2017, ISSN 1949-2553
Publisher: Impact Journals
DOI: 10.18632/oncotarget.19404

Human NUDT22 Is a UDP-Glucose/Galactose Hydrolase Exhibiting a Unique Structural Fold. Structure. Feb 6;26(2):295-303.e6.

Author(s): "Carter M, Jemth AS, Carreras-Puigvert J, Herr P, Martínez Carranza M, Vallin KSA, Throup A, Helleday T#, Stenmark P#."
Published in: Structure, 26/2, 2018, Page(s) 295-303.e6, ISSN 2352-0124
Publisher: Elsevier Limited
DOI: 10.1016/j.str.2018.01.004

OGG1 Inhibitor TH5487 Alters OGG1 Chromatin Dynamics and Prevents Incisions

Author(s): Bishoy M. F. Hanna, Thomas Helleday, Oliver Mortusewicz
Published in: Biomolecules, 10/11, 2020, Page(s) 1483, ISSN 2218-273X
Publisher: MDPI
DOI: 10.3390/biom10111483

NEIL1 and NEIL2 Are Recruited as Potential Backup for OGG1 upon OGG1 Depletion or Inhibition by TH5487

Author(s): Bishoy M. F. Hanna, Maurice Michel, Thomas Helleday, Oliver Mortusewicz
Published in: International Journal of Molecular Sciences, 22/9, 2021, Page(s) 4542, ISSN 1422-0067
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms22094542

Development of a chemical probe against NUDT15

Author(s): Si Min Zhang, Matthieu Desroses, Anna Hagenkort, Nicholas C. K. Valerie, Daniel Rehling, Megan Carter, Olov Wallner, Tobias Koolmeister, Adam Throup, Ann-Sofie Jemth, Ingrid Almlöf, Olga Loseva, Thomas Lundbäck, Hanna Axelsson, Shruti Regmi, Antonio Sarno, Andreas Krämer, Linda Pudelko, Lars Bräutigam, Azita Rasti, Mona Göttmann, Elisée Wiita, Juliane Kutzner, Torsten Schaller, Christina Kal
Published in: Nature Chemical Biology, 16/10, 2020, Page(s) 1120-1128, ISSN 1552-4450
Publisher: Nature Publishing Group
DOI: 10.1038/s41589-020-0592-z

MTH1 as a target to alleviate T cell driven diseases by selective suppression of activated T cells

Author(s): Stella Karsten, Roland Fiskesund, Xing-Mei Zhang, Petra Marttila, Kumar Sanjiv, Therese Pham, Azita Rasti, Lars Bräutigam, Ingrid Almlöf, Maritha Marcusson-Ståhl, Carolina Sandman, Björn Platzack, Robert A. Harris, Christina Kalderén, Karin Cederbrant, Thomas Helleday, Ulrika Warpman Berglund
Published in: Cell Death & Differentiation, 2020, ISSN 1350-9047
Publisher: Nature Publishing Group
DOI: 10.1038/s41418-021-00854-4

Computational and Experimental Druggability Assessment of Human DNA Glycosylases

Author(s): Maurice Michel, Torkild Visnes, Evert J. Homan, Brinton Seashore-Ludlow, Mattias Hedenström, Elisée Wiita, Karl Vallin, Cynthia B. J. Paulin, Jiaxi Zhang, Olov Wallner, Martin Scobie, Andreas Schmidt, Annika Jenmalm-Jensen, Ulrika Warpman Berglund, Thomas Helleday
Published in: ACS Omega, 4/7, 2019, Page(s) 11642-11656, ISSN 2470-1343
Publisher: MDPI
DOI: 10.1021/acsomega.9b00162

Correction: Glioblastoma and glioblastoma stem cells are dependent on functional MTH1

Author(s): Linda Pudelko, Pegah Rouhi, Kumar Sanjiv, Helge Gad, Christina Kalderén, Andreas Höglund, Massimo Squatrito, Alberto J. Schuhmacher, Steven Edwards, Daniel Hägerstrand, Ulrika Warpman Berglund, Thomas Helleday, Lars Bräutigam
Published in: Oncotarget, 11/8, 2020, Page(s) 827-827, ISSN 1949-2553
Publisher: Impact Journals
DOI: 10.18632/oncotarget.27484

MTH1 inhibitor TH588 induces mitosis-dependent accumulation of genomic 8-oxodG and disturbs mitotic progression

Author(s): Sean G Rudd, Helge Gad, Nuno Amaral, Anna Hagenkort, Petra Groth, Cecilia E Ström, OliverMortusewicz, Ulrika Warpman Berglund, Thomas Helleday
Published in: bioRxiv, 2019
Publisher: bioRxiv
DOI: 10.1101/573931

MTH1 promotes mitotic progression to avoid oxidative DNA damage in cancer cells

Author(s): Helge Gad, Oliver Mortusewicz, Sean G Rudd, Ailine Stolz, Nuno Amaral, Lars Brautigham, Linda Pudelko, Kumar Sanjiv, Christina Kaldéren, Ann-Sofie Jemth, Ingrid Almlöf, Torkild Visnes, Niklas Schultz, JohanBoström, José Manuel Calderon Montano, Anna Hagenkort, Petra Groth, Olga Loseva, Camilla Gokturk, Tobias Koolmeister, Prasad Wakchaure, Evert Homan, Cecilia E Ström, Martin Scobie, Holger
Published in: 2019
Publisher: bioRxiv
DOI: 10.1101/575290