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1. Genome-scale functional genomics identify genes preferentially essential for multiple myeloma cells compared to other neoplasias

Author

de Matos Simoes, Ricardo, Shirasaki, Ryosuke, Downey-Kopyscinski, Sondra L., Matthews, Geoffrey M., Barwick, Benjamin G., Gupta, Vikas A., Dupéré-Richer, Daphné, Yamano, Shizuka, Hu, Yiguo, Sheffer, Michal, Dhimolea, Eugen, Dashevsky, Olga, Gandolfi, Sara, Ishiguro, Kazuya, Meyers, Robin M., Bryan, Jordan G., Dharia, Neekesh V., Hengeveld, Paul J., Brüggenthies, Johanna B., Tang, Huihui, Aguirre, Andrew J., Sievers, Quinlan L., Ebert, Benjamin L., Glassner, Brian J., Ott, Christopher J., Bradner, James E., Kwiatkowski, Nicholas P., Auclair, Daniel, Levy, Joan, Keats, Jonathan J., Groen, Richard W. J., Gray, Nathanael S., Culhane, Aedin C., McFarland, James M., Dempster, Joshua M., Licht, Jonathan D., Boise, Lawrence H., Hahn, William C., Vazquez, Francisca, Tsherniak, Aviad, and Mitsiades, Constantine S.

Published
2023
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2. Functional Genomics Identify Distinct and Overlapping Genes Mediating Resistance to Different Classes of Heterobifunctional Degraders of Oncoproteins

Author

Shirasaki, Ryosuke, Matthews, Geoffrey M., Gandolfi, Sara, de Matos Simoes, Ricardo, Buckley, Dennis L., Raja Vora, Joseline, Sievers, Quinlan L., Brüggenthies, Johanna B., Dashevsky, Olga, Poarch, Haley, Tang, Huihui, Bariteau, Megan A., Sheffer, Michal, Hu, Yiguo, Downey-Kopyscinski, Sondra L., Hengeveld, Paul J., Glassner, Brian J., Dhimolea, Eugen, Ott, Christopher J., Zhang, Tinghu, Kwiatkowski, Nicholas P., Laubach, Jacob P., Schlossman, Robert L., Richardson, Paul G., Culhane, Aedin C., Groen, Richard W.J., Fischer, Eric S., Vazquez, Francisca, Tsherniak, Aviad, Hahn, William C., Levy, Joan, Auclair, Daniel, Licht, Jonathan D., Keats, Jonathan J., Boise, Lawrence H., Ebert, Benjamin L., Bradner, James E., Gray, Nathanael S., and Mitsiades, Constantine S.

Published
2021
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4. Targeting p38 or MK2 Enhances the Anti-Leukemic Activity of Smac-Mimetics

Author

Lalaoui, Najoua, Hänggi, Kay, Brumatti, Gabriela, Chau, Diep, Nguyen, Nhu-Y.N., Vasilikos, Lazaros, Spilgies, Lisanne M., Heckmann, Denise A., Ma, Chunyan, Ghisi, Margherita, Salmon, Jessica M., Matthews, Geoffrey M., de Valle, Elisha, Moujalled, Donia M., Menon, Manoj B., Spall, Sukhdeep Kaur, Glaser, Stefan P., Richmond, Jennifer, Lock, Richard B., Condon, Stephen M., Gugasyan, Raffi, Gaestel, Matthias, Guthridge, Mark, Johnstone, Ricky W., Munoz, Lenka, Wei, Andrew, Ekert, Paul G., Vaux, David L., Wong, W. Wei-Lynn, and Silke, John

Published
2016
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5. Supplementary Methods, Figures 1 - 3, Tables 1 - 3 from Molecular and Biologic Analysis of Histone Deacetylase Inhibitors with Diverse Specificities

Author

Newbold, Andrea, primary, Matthews, Geoffrey M., primary, Bots, Michael, primary, Cluse, Leonie A., primary, Clarke, Christopher J.P., primary, Banks, Kellie-Marie, primary, Cullinane, Carleen, primary, Bolden, Jessica E., primary, Christiansen, Ailsa J., primary, Dickins, Ross A., primary, Miccolo, Claudia, primary, Chiocca, Susanna, primary, Kral, Astrid M., primary, Ozerova, Nicole D., primary, Miller, Thomas A., primary, Methot, Joey L., primary, Richon, Victoria M., primary, Secrist, J. Paul, primary, Minucci, Saverio, primary, and Johnstone, Ricky W., primary

Published
2023
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15. Functional Characterization of E3 Ligases and Their Regulators: Therapeutic Implications for Development of New Proteolysis-Targeting Chimeric Degraders of Oncoproteins

Author

Shirasaki, Ryosuke, primary, Gandolfi, Sara, primary, De Matos Simoes, Ricardo, primary, Matthews, Geoffrey M, primary, Buckley, Dennis, primary, Raja, Joseline, primary, Sievers, Quinlan L, primary, Dashevsky, Olga, primary, Poarch, Haley, primary, Tang, Huihui, primary, Bariteau, Megan, primary, Sheffer, Michal, primary, Downey-Kopyscinski, Sondra L., primary, Hengeveld, Paul, primary, Glassner, Brian, primary, Dhimolea, Eugen, primary, Ott, Christopher J., primary, Zhang, Tinghu, primary, Kwiatkowski, Nicholas P, primary, Laubach, Jacob P., primary, Schlossman, Robert L., primary, Richardson, Paul G., primary, Culhane, Aedin, primary, Groen, Richard W.J., primary, Fischer, Eric, primary, Ebert, Benjamin L., primary, Vazquez, Francisca, primary, Tsherniak, Aviad, primary, Hahn, William C., primary, Levy, Joan, primary, Auclair, Daniel, primary, Licht, Jonathan D., primary, Keats, Jonathan J, primary, Boise, Lawrence H., primary, Bradner, James, primary, Gray, Nathanael, primary, and Mitsiades, Constantine S., primary

Published
2019
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16. Abstract LB-118: Characterization of lineage vs. context-dependent essential genes in multiple myeloma using CRISPR-Cas9 genome editing

Author

Matthews, Geoffrey M., primary, Simoes, Ricardo de Matos, additional, Hu, Yiguo, additional, Sheffer, Michal, additional, Dashevsky, Olga, additional, Dhimolea, Eugen, additional, Hengeveld, Paul J., additional, Glassner, Brian J., additional, Gandolfi, Sara, additional, Bariteau, Megan A., additional, Sievers, Quinlan, additional, Ebert, Benjamin L., additional, Vazquez, Franciska, additional, Culhane, Aedin, additional, and Mitsiades, Constantine S., additional

Published
2017
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17. Genomic characterisation of Eμ-Myc mouse lymphomas identifies Bcor as a Myc co-operative tumour-suppressor gene

Author

Lefebure, Marcus, primary, Tothill, Richard W., additional, Kruse, Elizabeth, additional, Hawkins, Edwin D., additional, Shortt, Jake, additional, Matthews, Geoffrey M., additional, Gregory, Gareth P., additional, Martin, Benjamin P., additional, Kelly, Madison J., additional, Todorovski, Izabela, additional, Doyle, Maria A., additional, Lupat, Richard, additional, Li, Jason, additional, Schroeder, Jan, additional, Wall, Meaghan, additional, Craig, Stuart, additional, Poortinga, Gretchen, additional, Cameron, Don, additional, Bywater, Megan, additional, Kats, Lev, additional, Gearhart, Micah D., additional, Bardwell, Vivian J., additional, Dickins, Ross A., additional, Hannan, Ross D., additional, Papenfuss, Anthony T., additional, and Johnstone, Ricky W., additional

Published
2017
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18. The Drug Vehicle and Solvent N-Methylpyrrolidone Is an Immunomodulator and Antimyeloma Compound

Author

Shortt, Jake, Hsu, Andy K., Martin, Benjamin P., Doggett, Karen, Matthews, Geoffrey M., Doyle, Maria A., Ellul, Jason, Jockel, Tina E., Andrews, Daniel M., Hogg, Simon J., Reitsma, Andrea, Faulkner, David, Bergsagel, P. Leif, Chesi, Marta, Heath, Joan K., Denny, William A., Thompson, Philip E., Neeson, Paul J., Ritchie, David S., McArthur, Grant A., and Johnstone, Ricky W.

Published
2014
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20. Characterization of Lineage Vs. Context-Dependent Essential Genes in Multiple Myeloma Using Crispr/Cas9 Genome Editing

Author

Matthews, Geoffrey M., primary, De Matos Simoes, Ricardo, additional, Hu, Yiguo, additional, Sheffer, Michal, additional, Dhimolea, Eugen, additional, Hengeveld, Paul J., additional, Bariteau, Megan A., additional, Glassner, Brian, additional, Sievers, Quinlan, additional, Ebert, Benjamin L., additional, Gandolfi, Sara, additional, Awate, Pallavi, additional, Tang, Huihui, additional, Vazquez, Franciska, additional, Culhane, Aedin, additional, and Mitsiades, Constantine S, additional

Published
2016
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21. Integrated Evaluation of Results from Genome-Wide Association Studies and Crispr/Cas9-Based Functional Genomics in Myeloma: Implications for Cell-Autonomous Vs. Non-Autonomous Role of Candidate Genes in Myeloma Pathophysiology

Author

De Matos Simoes, Ricardo, primary, Matthews, Geoffrey M., additional, Hu, Yiguo, additional, Glassner, Brian, additional, Bariteau, Megan A., additional, Sheffer, Michal, additional, Shirasaki, Ryosuke, additional, and Mitsiades, Constantine S, additional

Published
2016
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24. Constitutive Vs. Stroma-Induced Kinase Dependencies in Myeloma Cells: Functional Mapping Using Small Molecule Inhibitors As Chemical Probes

Author

Dhimolea, Eugen, primary, King, Emily, additional, Sheffer, Michal, additional, Hu, Yiguo, additional, Awate, Pallavi P., additional, Sarkar, Subhashis, additional, Matthews, Geoffrey M., additional, Murnane, Megan, additional, Bariteau, Megan A., additional, Aftab, Blake T., additional, and Mitsiades, Constantine S, additional

Published
2015
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27. Molecular and Biologic Analysis of Histone Deacetylase Inhibitors with Diverse Specificities

Author

Newbold, Andrea, primary, Matthews, Geoffrey M., additional, Bots, Michael, additional, Cluse, Leonie A., additional, Clarke, Christopher J.P., additional, Banks, Kellie-Marie, additional, Cullinane, Carleen, additional, Bolden, Jessica E., additional, Christiansen, Ailsa J., additional, Dickins, Ross A., additional, Miccolo, Claudia, additional, Chiocca, Susanna, additional, Kral, Astrid M., additional, Ozerova, Nicole D., additional, Miller, Thomas A., additional, Methot, Joey L., additional, Richon, Victoria M., additional, Secrist, J. Paul, additional, Minucci, Saverio, additional, and Johnstone, Ricky W., additional

Published
2013
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35. 13C-Urea breath test: Reproducibility and association with the severity ofHelicobacter pylori-associated antral gastritis.

Author

MATTHEWS, GEOFFREY M, CUMMINS, ADRIAN G, Lawrence, Andrew, JOHNSON, BRUCE, CAMPBELL, FIONA, and BUTLER, ROSS N

Subjects
*BREATH tests, *UREA, *INFLAMMATION, *HELICOBACTER pylori infections, *GASTRITIS, *BACTERIAL diseases
Abstract

The purpose of the present paper was to assess the reproducibility of the13C-urea breath test (13C-UBT) and its ability to reflect the level ofHelicobacter pylori-associated inflammation.AsymptomaticH. pylori-positive subjects (n = 21) performed the13C-UBT six times. TheH. pylori-positive symptomatic subjects (n = 55) performed the13C-UBT and had antral biopsies taken for histopathology, culture, urease activity assay and myeloperoxidase activity assay.No significant intraindividual variation in13C-UBT results were observed for the asymptomatic subjects. The13C-UBT results were significantly higher in symptomatic subjects with a moderate to severe gastritis compared to a mild gastritis and to no inflammation (34.5 ± 4.4 vs 17.7 ± 2.8 vs 1.7 ± 0.1, respectively,P < 0.01). The13C-UBT results significantly correlated with urease (r = 0.55) and myeloperoxidase activity (r = 0.82) but not with bacterial load.The13C-UBT is a reproducible determinant ofH. pyloriinfection and non-invasively assesses the severity of antral inflammation.© 2004 Blackwell Publishing Asia Pty Ltd [ABSTRACT FROM AUTHOR]

Published
2005
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37. Writing design

Author

Matthews, Geoffrey M. and Matthews, Geoffrey M.

Abstract

[Abstract]

39. Short-chain fatty acids induce apoptosis in colon cancer cells associated with changes to intracellular redox state and glucose metabolism

Author

Gordon S. Howarth, Ross N. Butler, Geoffrey M. Matthews, Matthews, Geoffrey M, Howarth, Gordon S, and Butler, Ross N

Subjects
Colorectal cancer, glucose metabolism, Apoptosis, Butyrate, Carbohydrate metabolism, digestive system, Drug Discovery, medicine, Humans, Pharmacology (medical), propionate, Mode of action, Pharmacology, Chemistry, Short-chain fatty acid, digestive, oral, and skin physiology, apoptosis, General Medicine, Fatty Acids, Volatile, medicine.disease, butyrate, Glutathione, G2 Phase Cell Cycle Checkpoints, Butyrates, Glucose, Infectious Diseases, Oncology, Biochemistry, colon cancer, Caco-2, redox, Colonic Neoplasms, M Phase Cell Cycle Checkpoints, cell cycle, Caco-2 Cells, Propionates, Reactive Oxygen Species, short-chain fatty acid, Oxidation-Reduction, Intracellular
Abstract

Background: Short-chain fatty acids (SCFA) are undergoing increased scrutiny as chemotherapeutics for colon cancer, although a comprehensive understanding of their mode of action is lacking. We investigated candidate SCFA for their capability to modulate apoptosis, cell cycle, intracellular redox state and glucose metabolism in the Caco-2 human colon cancer cell line. Methods: Caco-2 cells were incubated with butyrate, propionate or a combination of these SCFA (1:1) and assessed by flow cytometry, enzyme activity analysis or by isotope ratio mass spectrometry. Results: Butyrate and the SCFA combination induced apoptosis and G2-M arrest to a greater extent than propionate alone (p < 0.05). SCFA treatment led to time-dependent alterations to the oxidative pentose pathway, reductions in glutathione availability and increases in levels of reactive oxygen species (p < 0.05) compared with untreated controls. The rate of D-glucose metabolism was increased by all SCFA, although to the greatest extent by butyrate (p < 0.05). Conclusions: These results suggest that butyrate, or the combination of both SCFA, induced rapid and extensive apoptosis and G2-M arrest associated with changes to redox state and D-glucose metabolism. These results support the potential for butyrate and propionate to act as adjuncts to conventional chemotherapy regimens for colon cancer.

Published
2012

40. Highly specific intracellular ubiquitination of a small molecule.

Author

Li W, Garcia-Rivera EM, Mitchell DC, Chick JM, Maetani M, Knapp JM, Matthews GM, Shirasaki R, de Matos Simoes R, Viswanathan V, Pulice JL, Rees MG, Roth JA, Gygi SP, Mitsiades CS, Kadoch C, Schreiber SL, and Ostrem JML

Abstract

Ubiquitin is a small, highly conserved protein that acts as a posttranslational modification in eukaryotes. Ubiquitination of proteins frequently serves as a degradation signal, marking them for disposal by the proteasome. Here, we report a novel small molecule from a diversity-oriented synthesis library, BRD1732, that is directly ubiquitinated in cells, resulting in dramatic accumulation of inactive ubiquitin monomers and polyubiquitin chains causing broad inhibition of the ubiquitin-proteasome system. Ubiquitination of BRD1732 and its associated cytotoxicity are stereospecific and dependent upon two homologous E3 ubiquitin ligases, RNF19A and RNF19B. Our finding opens the possibility for indirect ubiquitination of a target through a ubiquitinated bifunctional small molecule, and more broadly raises the potential for posttranslational modification in trans ., Competing Interests: JMLO holds equity in Araxes Pharma and receives research funds from Ono Pharma. SLS is a shareholder and serves on the Board of Directors of Kojin Therapeutics; is a shareholder and advises Jnana Therapeutics, Kisbee Therapeutics, Belharra Therapeutics, Magnet Biomedicine, Exo Therapeutics, Eikonizo Therapeutics, and Replay Bio; advises Vividion Therapeutics, Eisai Co., Ltd., Ono Pharma Foundation, F-Prime Capital Partners, and is a Novartis Faculty Scholar. CK is the scientific founder, Scientific Advisor to the Board of Directors, Scientific Advisory Board member, shareholder, and consultant for Foghorn Therapeutics. CK also serves on the Scientific Advisory Boards of Nereid Therapeutics (shareholder and consultant), Nested Therapeutics (shareholder and consultant), Accent Therapeutics (shareholder and consultant), and Fibrogen (consultant) and is a consultant for Cell Signaling Technologies and Google Ventures (shareholder and consultant). EMGR is an employee of BullFrog AI. DCM is an employee of Flagship Pioneering. JMC is an employee of Odyssey Therapeutics. MM is an employee of Intellia Therapeutics. GM is an employee of Aculeus Therapeutics. VV is an employee of Kojin Therapeutics. None of these relationships influenced this study. The other authors declare no competing interests. C.S.M. serves on the Scientific Advisory Board of Adicet Bio and discloses consultant/honoraria from Genentech, Fate Therapeutics, Ionis Pharmaceuticals, FIMECS, Secura Bio and Oncopeptides, and research funding from EMD Serono, Karyopharm, Sanofi, Nurix, BMS, H3 Biomedicine/Eisai, Springworks, Abcuro, Novartis and OPNA. RS received honoraria and research funding from FIMECS and Janssen Pharmaceutical K.K. Japan. The remaining authors declare no competing interests. None of the above companies played a role in data acquisition, data analysis, manuscript preparation, or in the decision to publish.

Published
2024
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