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Thomas Begley

Thomas Begley
Associate Professor of Nanobioscience; Associate Vice President and Director of the Systems Toxicology Laboratory

Education:

  • Post Doctoral Fellow, Division of Biological Engineering and Center for Environmental Health Sciences, Massachusetts Institute of Technology, 2004
  • Post Doctoral Associate, Department of Cancer Cell Biology, Harvard School of Public Health, 2002
  • Ph.D., Biological Sciences, with a concentration in Molecular Biology, University at Albany, State University of New York, 2000

Past Professional Experience:

  • Associate Professor, with tenure, Department of Biomedical Sciences and Cancer Research Center, University at Albany, State University of New York, 2010
  • Assistant Professor, Department of Biomedical Sciences and Gen*NY*Sis Center for Excellence in Cancer Genomics, University at Albany, State University of New York, 2004

Areas of Research:

Research Description:

The long terms goals of my research program are to develop nanoscale based diagnostic tools and a knowledge base that promotes personalized medicine, specifically in the areas of environmental health, cancer prevention and treatment. Too much DNA damage or deficiencies in the cellular response to and repair of damaged DNA can promote cancer onset and progression. My research program is focused on identifying and characterizing chemicals and nanoscale materials that damage DNA. In addition, we are identifying molecular signaling pathways associated with the response to and repair of DNA damage. Corrupted DNA damage and stress responses can be associated with cancer onset and progression. My research team has identified a stress-signaling pathway associated with translational regulation that can turn off the growth of late stage (IV) colorectal tumors. We are characterizing proteins belonging to this growth suppression pathway for use in diagnostic applications, and plan on exploiting these proteins to develop cancer therapeutics. My research program is also evaluating the use of small molecules associated with translational signaling (i.e., modified tRNA nucleosides), as biomarkers of environmental stress, DNA damage and inflammation, as they have the potential to serve as indicators of disease onset or progression. The molecular signaling potential of these modifications is also being analyzed using computational and wet bench tools, with the long-term goal of cracking a post-transcriptional stress code. We are also developing Nanoscale tools and high content immuno-based assays that will be used to assess an individuals DNA repair capacity, with these assays having applications in cancer diagnostics, occupational and environmental health.

Recent Honors and Awards:

  • Career, Leadership and University Excellence (CLUE) Training Fellow, University at Albany, SUNY
  • Visiting Scholar, Department of Environmental Health and Engineering, University of North Carolina Chapel Hill
  • Outstanding New Investigator in Environmental Health Sciences (ONES) Award, National Institutes of Environmental Health Sciences, NIH
  • James D. Watson Investigator Award, New York State Office of Science and Technology (NYSTAR)
  • Transition to Independent Positions (T.I.P.) Award, National Institutes of Environmental Health Sciences, NIH
  • Merck-MIT Computational and Systems Biology Fellowship 
  • National Research Service Award, National Institutes of Environmental Health Sciences, NIH

Recent Publications:

Dyavaiah, M., Rooney, J., and, Lin, Q., Chittur, S., and Begley T. J., Degradation of Ribonucleotide Reductase 1 Links Autophagy to Regulation of the DNA Damage Response (in press) Molecular Cancer Research

Chan, C. T. Y., Dyavaiah, M., Taghizadeh, K., Dedon, P. C., and Begley, T. J., A quantitative systems approach reveals dynamic control of tRNA modifications during cellular stress. (in press) PloS Genetics

Rooney, J., Patil, Joseph, F., Endres, L., Begley, U. A., Zappala, M. R, Cunningham, R. P., and Begley T. J., Functional Interactome Analysis Identifies DNA Repair, Translation and Aerobic Respiration as Conserved Responses to UV-induced Damage (in press) Genomics

Sanders, M., Begley, T. J., Desaintes, C., Gavin, A., Pelroy, R., Shiloh, Y., van Gent, D., Van Houten, B., Yaffe, M., and Mullenders L. 3rd US-EU Workshop on Systems level understanding of DNA damage responses. 2010 Mutation Research. 692:53-60.

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. Human ABH8 is a tRNA methyltransferase with a role in DNA damage survival. 2010 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. Saccharomyces cerevisiae genome-wide deletion mutant screen for altered sensitivity and resistance to NiSO4. 2009 BMC Genomics 10:524

Zhou, X., Arita, A., Ellen, T.P., Rooney, J. P., Begley, T.J., and Costa, M. Genome-wide responses to arsenite in Saccharomyces cerevisiae. 2009 Genomics. 94:294-307.

Rooney, J., Patil, A., Zappala, M. R., Conklin, D. S., Cunningham, R. P., and Begley T. J. A Molecular Bar-Coded DNA Repair Resource for Pooled Toxicogenomic Screens. 2008. DNA Repair. 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 3:e3717.

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.

Begley, T.J. and Samson, L.D. 2004. Reversing DNA damage with a directional bias. Nat Struct Mol Biol 8: 688-690.

Begley, T.J. and Samson, L.D. 2004. Network responses to damaging agents. DNA Repair 3:1123-1132.

Begley, T.J. and Samson, L.D. 2003. AlkB mystery solved: Oxidative demethylation of N1-methyladenine and N3-methylcytosine adducts by a direct repair mechanism. Trends in Biochemical Sciences 28: 93-96.

Begley, T.J. and Samson, L.D. 2003. A fix for RNA. Nature 421: 795-796.

Begley, T.J., Haas, B.J., Morales, J.C., Kool, E.T., and Cunningham, R.P. 2003. Kinetics and binding of the thymine-DNA mismatch glycosylase, Mig-Mth, with mismatch-containing DNA substrates. DNA Repair 2: 107-120.

Mol, C.D., Arvai, A.S., Begley, T.J., Cunningham, R.P., and Tainer, J.A. 2002. Structure and activity of a thermostable thymine-DNA glycosylase: Evidence for base twisting to remove mismatched normal DNA bases. J Mol Biol 315: 373-384.

Begley, T.J., Rosenbach, A.S., Ideker, T. and Samson, L.D. 2002. Recovery pathways in S. cerevisiae revealed by genomic phenotyping and interactome mapping. Mol Cancer Res 1: 103-112.

Recent Invited Lectures and Presentations:

International

  • International Conference on Environmental Mutagens (ICEM), Florence, Italy,
  • European Union (EU)/United States (US) Workshop on Systems Level Understanding of DNA Damage Responses. Egmond aan Zee, Netherlands, 
  • University of Montreal, Maisonneuve-Rosemont Hospital Research Center, Montreal, Canada
  • NIH-EU Workshop on Systems Biology of Environmental Cancer, Bushmills, Northern Ireland
  • International Environmental Mutagen Society Meeting, Kos, Greece

National

  • Division of Biological Engineering, Massachusetts Institute of Technology
  • Center for Complex Systems, Northeastern University 
  • Department of Computational Biology & Pittsburgh Cancer Institute
  • Oncological Sciences, Mount Sinai School of Medicine
  • Society of Toxicology National Meeting, Baltimore MD
  • National Institute of Child Health and Development, NIH
  • American Chemical, Mechanisms of Chemically-Mediated Toxicity, American Chemical Society Symposium
  • DNA Repair Focus Group, University North Carolina-Chapel Hill
  • Department of Pharmacology and Toxicology, University Louisville, KY
  • Center for Cancer Systems Biology, Dana Farber – Harvard Medical School
  • Center for Environmental Health, NYU Medical School
  • National Institute of Environmental Health Sciences, NIH
  • Department of Engineering and Environmental Health, University of North Carolina at Chapel Hill 
  • Center in Molecular Toxicology, Vanderbilt University