Thomas Begley

Assistant Director of Research of the RNA Institute, Distinguished Professor of Biological Sciences, Director of Training in RNA Science and Technology, Interim REPR Director

Department of Biological Sciences

The RNA Institute

Contact

LS 2033

518-437-4443

[email protected]

Education

PhD, University at Albany

About

RNA Institute Website
The Begley Lab

DNA Repair & Genetic Toxicology
Environmental Health
Epitranscriptomics
Member of the Cancer Research Center
Member of the RNA Institute
tRNA Modifications & Translation

Research

Research Interests

Environmental and endogenous stressors can cause DNA damage to promote cancer onset, cancer progression and ageing. The overarching theme of my research program has been the study of cellular, tissue and organismal responses to stress, with an emphasis on alkylating agents and stressors that increase reactive oxygen species (ROS) levels. In addition, my research team participates in the development of technologies to study and mitigate cellular stress responses. Our long-term goal is to use information from our studies to define new mechanisms of signal transduction and to develop a knowledge base and tools to treat human disease.

Highlights of research in the Begley Laboratory include (1) the demonstration that epitranscriptomic marks found in the form of RNA modifications play key stress response roles, by regulating the translation of DNA damage and ROS response proteins, (2) the development of algorithms and database systems to identify nucleic acid sequences translationally regulated during stress responses, (3) the identification of a new tumor growth suppressor for colorectal cancer, and (4) the development of a mouse model that has increased ROS levels, for use in the testing of potential environmental hazards.

We have also collaboratively developed technology and used it to (1) characterize global changes in RNA modification in response to stress, (2) measure activation of the DNA damage response in patients undergoing diagnostic computerized tomography (CT) scans, and (3) have started work to develop single molecule approaches for the analysis of modified RNA nucleosides.

Major philosophies of our approach to research are to (1) perform exciting science that uses new technologies and concepts to expand our understanding of basic biology and disease conditions, (2) develop new approaches and technologies that can be used by other scientists, and (3) collaborate with other experts to perform state of the art team-based science.

Publications

Zheng, Y. Y., Wu, Y., Begley, T. J., and Sheng, J. Sulfur modification in natural RNA and therapeutic oligonucleotides. 2021. RSC Chemical Biology. 2 (4), 990-1003.
Sarkar, A., Gasperi, W., Begley, U., Nevins, S., Huber, S., Dedon, P. C., and Begley, T. J. Detecting the epitranscriptome. 2021. RNA Wires. May 13;e1663.
Hu, J.F., Yim, D., Ma, D., Huber, S. M., Davis, N., Bacusmo, J., Vermeulen, S., Zhou, J., Begley, T.J., DeMott, M.S., Levine, S.S., de Crécy-Lagard, V., Dedon, P.C., Cao. B. 2021. Quantitative mapping of the cellular small RNA landscape with AQRNA-seq. Nature Biotechnology. 39 (8), 978 - 988.
Mao, S., Haruehanroengra, P., Ranganathan, S. V., Shen,F., Begley, T. J., and Sheng, J. Base Pairing and Functional Insights into N3-methylcytidine (m3C) in RNA. 2020. ACS Chem Biol. 1, 76 - 85.
Nagaraja, S., Cai, M., Sun, J., Sarid, L., Trebicz-Geffen, M., Shaulov, Y., Mazumdar, M., Varet, H., Legendre, Jean-Yves Coppee, R., Begley, T.J., Dedon, P.C., Samudrala, G., Guillen, N., Saito-Nakano, Y., Shimokawa, H., Hisaeda, H., and Ankri, S. 2020. Queuine is a nutritional regulator of Entamoeba histolytica response to oxidative stress and a virulence attenuator. mBio Mar 2021, 12 (2) e03549-20.
Pollo-Oliveira, L., Klassen, R., Davis, N., Ciftci, A., Bacusmo, J.M., Martinelli, M., DeMott, M.S., Begley, T.J., Dedon, P.C., Schaffrath, R., de Crécy-Lagard, V. 2020. Loss of Elongator- and KEOPS-Dependent tRNA Modifications Leads to Severe Growth Phenotypes and Protein Aggregation in Yeast. Biomolecules. 10, 322.
Leonardi, A., Kovalchuk, N., Yin, L., Endres L., Evke S., Nevins, S., Martin, S., Dedon, P.C., Melendez, J.A., Van Winkle, L., Zhang, Q.Y., Ding, X., Begley, T.J. 2020. “The epitranscriptomic writer ALKBH8 drives tolerance and protects mouse lungs from the environmental pollutant naphthalene”. Epigenetics. Apr 17:1-18.
Lee, M., Leonardi, A., Begley, T.J., and Melendez, J.A. 2020. “Loss of epitranscriptomic control of selenocysteine utilization engages senescence and metabolic reprogramming”. Redox Biology. 28, 101375.
Leonardi, A., Evke, S., M. Lee, Melendez, J. A., and Begley, T.J. 2019. Epitranscriptomic Systems Regulate the Translation of Reactive Oxygen Species Detoxifying and Disease Linked Selenoproteins. Free Radic Biol Med. 143, 573-593.
Huber, S.M., Leonardi, A., Dedon, P.C., and Begley, T.J. 2019. The Versatile Roles of the tRNA Epitranscriptome during Cellular Responses to Toxic Exposures and Environmental Stress. Toxics. 7(1).
Chan, C., Pham, P., Dedon, P.C., and Begley, T.J. 2018. Lifestyle modifications: coordinating the tRNA epitranscriptome with codon bias to adapt translation during stress responses. Genome Biol. 19(1), 228.
Rothenberg, D.A., Taliaferro, J.M., Huber, S.M., Begley, T.J., Dedon, P.C., and White, F.M. 2018. A Proteomics Approach to Profiling the Temporal Translational Response to Stress and Growth. iScience. 5(9), 367-381.
Gu, C., Ramos, J., Begley, U., Fu, D., Dedon. P. C and Begley, T.J. 2018. Phosphorylation of TRM9L integrates multiple stress-signaling pathways for tumor growth suppression. Sci Adv., Jul; 4(7): eaas9184
Onanuga, K. A., Begley, T.J., Chen, A., and Ranganathan, S. V. 2017. tRNA Modification detection using graphene nanopores: a simulation study. Biomolecules, 7(3), 65; doi:10.3390/biom7030065
Hseih, Y., Begley, U., Hansen, A. F., Kaminsky, L., McCandless, B., and Begley, T.J. 2017. Activation of DNA damage signaling components by diagnostic computed tomography (CT) scans detected in patient samples using an electrochemiluminescence-based assay platform. Advances in Bioscience and Biotechnology, 8(7), 1 -20.
Sosa Pena, P., Begley, U., Begley, T.J., and J. A. Melendez. 2017. Mitochondrial Redox Control of Cancer. Semin Cancer Biol.
Nagel, Z., Engelward, B. P., Brenner, D. J., Begley, T.J., Sobol, R.W, Bielas, J., Stambrook, P., Wei, Q., Hu, J., Terry, M. B., Dilworth, C., McAllister, K.A., Reinlib, L., Worth, L., and Shaughnessy, D.T. 2017. Towards Precision Prevention, Identifying Healthy Individuals with High Risk of Disease. Mutat Res., 800-802, 14-28.
Chionh, Y.H., McBee, Ramesh Babu, I., Hia, F., Lin, W., Zhao, W., Cao, J., Dziergowska, A., Malkiewicz, A., Begley, T.J., Alonso, S., and Dedon P.C. 2016. tRNA-mediated Codon-biased Translation in Mycobacterial Hypoxic Persistence. Nature Communications, 7, 13302
Doyle, F., *Leonardi, A., Endres, L., Tenenbaum, S.A., Dedon, P.C. and Begley, T.J. 2016. Gene- and Genome-Based Analysis of Significant Codon Patterns in Yeast, Rat and Mice Genomes with the CUT Codon Utilization Tool. Methods., 107, 98-109.
Klionsky, D. J., Begley T. J., Zuckerbraun B. 2016. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy, 12(1), 1-222. (note, over 200 authors)
Deng, W, Babu, I.R., Su, D., Yin,S., Begley, T.J., and Dedon, P.C. 2015. Trm9-catalyzed tRNA modifications regulate global protein expression by codon-biased translation. PLoS Genet., 11(12), e1005706.
Endres., L., Dedon., P. C., and Begley, T.J. 2015. Codon-biased translation can be regulated by wobble-base tRNA modification systems during cellular stress responses. RNA Biol., 12(6), 603 -14.
Flaherty, N.L., Chandrasekaran, A., Sosa Pena, P., M. Roth, G., Brenner, S., Begley, T.J., and J. A. Melendez. 2015. Assessment of redox and inflammatory properties of commonly used industrial nanomaterials. Toxicol lett., 239(3), 205-15.
Cai, W.M., Chionh, Y.H., Hia, F., Gu, C., Kellner, S., McBee, M.E., Ng, C.S., Pang, Y.L., Prestwich, E.G., Lim, K.S., Ramesh Babu, I., Begley, T.J., and Dedon, P.C. 2015. A platform for discovery and quantification of modified ribonucleosides in RNA - application to stress-induced reprogramming of tRNA modifications. Methods Enzymol.,560, 29-71.
Endres., L., Begley, U., Clark., R., Gu, C., Dziergowska, A., Malkiewicz, A., Melendez., J. A., Chen, C., Dedon., P. C., and Begley, T.J. 2015. Alkbh8 regulates selenocysteine-protein expression to protect against reactive oxygen species damage. PLoS ONE, 10(7)e0131335.
Chan, C., T., Deng, W., Li, F., DeMott, M. S., Babu, I. R., Begley, T.J., and Dedon, P. C. 2015. Highly predictive reprogramming of tRNA modifications is linked to selective expression of codon-biased genes. Chem Res Toxic., 28, 978-88.
Gaupel, A., C., Begley, T.J., Tenniswood, M. 2015. Gcn5 modulates the cellular response to oxidative stress and histone deacetylase inhibition. J. Cell. Biochem., 116(9):1982-92.
Chen, C., and Begley, T.J., and Dedon., P. C. 2014. tRNA modifications regulate translation during cellular stress. Febs Lett., 588, 4287-96.
Gaupel, A., C., Begley, T.J., and Tenniswood, M. 2014. High throughput screening identifies modulators of histone deacetylase inhibitors. BMC Genomics, 15, 528-535.
Prasad Kovvuru, P., Mancilla, P. E., Shirode, A. B., Murray, T. M., Begley, T.J., and Reliene, R., 2014. Oral ingestion of silver nanoparticles induces genomic instability and DNA damage in multiple tissues. Nanotoxicology, 9, 162-71.
Su, D., Chan, C. T. Y., Gu, C., Lim, K. S., Chionh, Y. H., McBee, M. E., Russell, B. S., Babu, I. R., Begley, T.J., and Dedon, P. C. 2014. Quantitative analysis of tRNA modifications by HPLC-coupled mass spectrometry. Nature Methods, 9, 828-41.
Dedon, P. C., and Begley, T.J. 2014. Perspective: A system of RNA modifications and biased codon use control cellular stress response at the level of translation. Chem. Rev. Tox., 27, 330-7.
Shaughnessy, D. T., McAllister, K. A., Worth Jr, L. W., Haugen, A. C., Meyer, J. N., Domann, F. E., Van Houten, B., Mostoslavsky, R., Bultman, S. J., Baccarelli, A. A., Begley, T.J., Sobol, R. W., Hirschey, M. D., Ideker, T., Santos, J., Copeland, W., Tice, R., Balshaw, D. M., Tyson, F. L. 2014. Mitochondria, Energetics, Epigenetics, and Cellular Responses to Stress. Environ Health Persp., 12, 1271-1278.
Lamichhane, T.N., Blewett, N.H., Crawford, A.K., Cherkasova, V.A., Iben, J.R., Begley, T.J., Farabaugh, P.J., Maraia, R.J., 2013. Lack of tRNA modification isopentenyl-A37 alters mRNA decoding and causes metabolic deficiencies. Mol Cell Biol., 33, 1 8.
Begley, U., Sosa, M. S., Avivar-Valderas, A., Patil, A., Endres, L., Yeriel Estrada, Y., Chan, C. T. Y., Su, D., Dedon, P. C., Aguirre-Ghiso, J. A., and Begley, T.J. 2013. Human tRNA methyltransferase 9 like protein prevents tumor growth by regulating LIN9 and HIF1a. 2013 EMBO Molecular Medicine., 5, 1 18.
Svilar D., Dyavaiah M., Brown A.R., Tang J.B., Li J., McDonald P.R., Shun T.Y., Braganza A., Wang X.H., Maniar, S., St Croix, C.M., Lazo J.S., Pollack I.F., Begley, T.J., Sobol R.W. 2012. Alkylation sensitivity screens reveal a conserved cross-species functionome. Mol Cancer Res., 10, 1580-96. (Highlighted on the Cover)
Klionsky, D. J., Begley, T.J., Zuckerbraun, B. 2012. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy., 8 445-544. (note over 200 authors)
Patil, A., Dyavaiah, M., Rooney, J., Joseph, F., Chan, C. T. Y., Dedon, P. C. and Begley, T.J. 2012. Increased tRNA modification and gene-specific codon usage regulate cell cycle progression during the DNA damage response. Cell Cycle,11, 3656 - 65. (Highlighted in Chemical Reviews in Toxicology)
Patil, A., Dyavaiah, M., Rooney, J., Chan, C. T. Y., Dedon, P. C. and Begley, T.J. 2012. Translational infidelity-induced protein stress results from a deficiency in Trm9-catalyzed tRNA modifications. RNA Biology, 9, 990 – 1001.
Chan, C. T. Y., Pang, Y. L. J., Babu, I. R., Dyavaiah, Begley, T.J., and Dedon, P. C. 2012. Reprogramming of tRNA modifications controls the oxidative stress response by selective translation of ribosomal protein paralogs. Nature Communications, 3, 937 – 945.
Towns, W., and Begley, T.J. 2012. tRNA Methytransferases and Their Corresponding Modifications in Budding Yeast and Humans Activities, Predications and Potential Roles in Human Health. DNA and Cell Biology, 4, 434-54.
Tumu, S., Dyavaiah, M., Towns, W., Patil, A., and Begley, T.J. 2012. The Gene Specific Codon Counting Database, A genome-based catalog of one, two, three, four and five codon combinations present in Saccharomyces cerevisiae genes. Database, Feb 8, 2012bas002.
Dyavaiah, M., Rooney, J., and, Lin, Q., Chittur, S., and Begley, T.J. 2011. Autophagy-Dependent Regulation of the DNA Damage Response Protein Ribonucleotide Reductase 1. Mol Cancer Res., 9, 101-114. (Highlighted on the cover)
Rooney, J., Patil, Joseph, F., Endres, L., Begley, U., Zappala, M. R, Cunningham, R. P., and Begley, T.J. 2011. Cross-species Functionome analysis identifies proteins associated with DNA repair, translation and aerobic respiration as conserved modulators of UV-toxicity. Genomics, 97, 133-147. (Highlighted on the cover)
Chan, C. T. Y., Dyavaiah, M., Taghizadeh, K., Dedon, P. C., and Begley, T.J., 2010. A quantitative systems approach reveals dynamic control of tRNA modifications during cellular stress. PloS Genetics, 6(12), e1001247. (Highlighted in Nature Methods)
Sanders, M., Begley, T.J., Desaintes, C., Gavin, A., Pelroy, R., Shiloh, Y., van Gent, D., Van Houten, B., Yaffe, M., and Mullenders L. 2010. 3rd US-EU Workshop on Systems level understanding of DNA damage responses. Mutation Research, 9, 69253-60.
Fu, D., Atmore, K. A., Brophy, J., Chan, C., T., Y., Begley, U., Paules, R. S., Dedon, P., C., Begley, T.J., and Samson, L. D. 2010. Human AlkB homolog ABH8 Is a tRNA methyltransferase required for wobble uridine modification and DNA damage survival. Mol Cell Biol., 10, 2449-59.
Arita, A., Zhou, X., Ellen, T.P., Liu,X., Rooney, J. P., Kutz, A., Klein, C.B., Dai, W., Begley, T.J., and Costa, M. 2009. A genome-wide deletion mutant screen identifies pathways affected by nickel sulfate in Saccharomyces cerevisiae. BMC Genomics, 10, 524.
Zhou, X., Arita, A., Ellen, T.P., Rooney, J. P., Begley, T.J., and Costa, M. 2009. A genome-wide screen in Saccharomyces cerevisiae reveals pathways affected by arsenic toxicity. Genomics, 94, 294-307.
Rooney, J., Patil, A., Zappala, M. R., Conklin, D. S., Cunningham, R. P., and Begley T. J. 2008. A Molecular Bar-Coded DNA Repair Resource for Pooled Toxicogenomic Screens. 7 1855-68.
Erlich, R.L., Fry, R.C., Begley, T.J., Daee D.L., Lahue R.S., Samson L.D. 2008. Anc1, a protein associated with multiple transcription complexes, is involved in postreplication repair pathway in S. cerevisiae. PLoS ONE ,3e, 3717.
Rooney, J., George, A. J., Patil, A., Bessette, E., Begley, U., Zappala, M. R., Huang, X., Conklin, D. S., Cunningham, R. P., and Begley, T.J. 2008. Systems-Based Mapping Identifies DNA Repair and Translational Networks Affecting Alkylation Induced Toxicity. Genomics, 93, 42-51.
Begley, U., Dyavaiah, M., Patil, A., Rooney. DiRenzo, D., Young. C, Conklin, D. S. Zitomer, R. S. and, Begley, T.J. 2007. Trm9 Catalyzed tRNA Modifications Link Translation to the DNA Damage Response. Molecular Cell., 28, 860-870. (Highlighted in Faculty of 1000 and News and Views in Nature Chemical Biology)
Rusyn I., Fry R.C., Begley, T.J., Klapacz J., Svensson J.P., Ambrose M., Samson L.D. 2007. Transcriptional Networks in S. cerevisiae Linked to an Accumulation of Base Excision Repair Intermediates. PLoS ONE, 2(11), 1252-1260.
Fry, R., DeMott, M., Cosgrove, J. Begley, T.J., Samson, L. D., and Dedon, P. 2006. The DNA-damage signature in Saccharomyces cerevisiae is associated with single-strand breaks in DNA. BMC Genomics, 7, 313-20.
Workman, C. T., Mak, H. C., McCuine, S., Tagne, J. B., Agarwal, M., Ozier, O., Begley, T.J., Samson, L. D, and Ideker T. 2006. A systems approach to mapping DNA damage response pathways. Science, 312, 1054-9.
Begley, T.J. 2005. Interactomes as a base unit in systems biology. Biosystems, 1, 2-8.
Fry, R.C., Begley, T.J., and Samson, L.D. 2005. Genome-wide responses to DNA-damaging agents. Annu Rev Microbiol., 59, 357-377.
Said, M.R.*, Begley, T.J., Oppenheim, A.V., Lauffenburger, D.A. and Samson, L.D. 2004. Global network analysis of phenotypic effects Protein networks and S. cerevisiae damage recovery. PNAS, 52, 18006-11.
Begley, T.J., Rosenbach, A.S., Ideker, T., and Samson, L.D. 2004. Hot spots for toxicity modulation identified by genomic phenotyping and localization mapping. Molecular Cell., 16, 117-125.