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Richard S. Paules, Ph.D.

Acting Chief, Biomolecular Screening Branch

Richard S. Paules, Ph.D.
Richard S. Paules, Ph.D.
Acting Chief, Biomolecular Screening Branch
Tel 984-287-3171
paules@niehs.nih.gov
P.O. Box 12233
Mail Drop K2-17
Durham, N.C. 27709

Richard S. Paules, Ph.D., is the Acting Chief of the Biomolecular Screening Branch (BSB) in the Division of the National Toxicology Program at the National Institute of Environmental Health Sciences (NIEHS), NIH. He also holds adjunct faculty appointments as Professor in the Department of Pathology and Laboratory Medicine and Member in the Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill.

tox21

The Biomolecular Screening Branch (BSB) develops and carries out programs in medium and high throughput screening of environmental substances for rapid detection of biological activities of significance to toxicology. The branch administers the NTP high-throughput screening (HTS) program initiative to implement its vision for toxicology in the 21st century. This NTP vision places an increased emphasis on the use of alternative assays for targeting the key pathways, molecular events, or processes linked to disease or injury, and attempts to incorporate them into a research and testing framework. In support of this program, BSB scientists represent NTP in the Toxicology in the 21st Century (Tox21) Partnership, which includes NTP, United States Environmental Protection Agency, U.S. Food and Drug Administration, and the National Center for Advancing Translational Sciences (NCATS) at NIH.

The research interests of Paules include integrating conventional studies of environmental exposures and toxicity with global "omics" approaches, or toxicogenomics. These efforts are designed to relate alterations in global gene expression to adverse events as defined by conventional parameters of toxicity and pathology, with the ultimate goal of applying genomic information to human risk assessment. Additionally, toxicogenomic studies are being performed to provide insight into mechanisms of injury and disease as well as to establish signatures of adverse effects to develop putative biomarkers of exposure or adverse effects. Paules is also involved in the application of new approaches to understand genetic and epigenetic differences in susceptibility to toxicity and disease. Using the tools of toxicology, bioinformatics and comparative genetic analysis, the identification of human orthologs of causally related animal genes will aid the extrapolation between animal models and human toxicity and disease related to environmental, occupational, and/or medicinal exposures.

Paules received his Ph.D. from the Department of Pathology at the University of North Carolina at Chapel Hill and then received postdoctoral training with George F. Vande Woude at the National Cancer Institute, NIH before joining NIEHS in 1990. At NIEHS, Paules lead a research group in the Division of Intramural Research for over 20 years that investigated the signal transduction pathways that control cell cycle arrest and DNA damage signaling following double stranded DNA breaks, signaling pathways that involve the ATM, ATR and DNA-PK protein kinases. He also served as director of the NIEHS Microarray Core and the NIEHS Molecular Genomics Core Facility, utilizing genomic approaches to investigate DNA damage responses on a systems biology level. This research interest expanded to investigation of biological stress responses to environmental exposures in a new field referred to as toxicogenomics, an interest that he brought to the Division of the National Toxicology Program, NIEHS, when he joined in 2013.

He has authored approximately 100 peer-reviewed articles in leading biomedical journals, as well as 19 book chapters and invited publications. He holds appointments as Adjunct Professor in the Department of Pathology and Laboratory Medicine and Adjunct Member of the Lineberger Comprehensive Cancer Center at University of North Carolina at Chapel Hill. He also serves as Associate Editor of BMC Genomics and serves on the Editorial Board of Current Opinion in Toxicology and the Editorial Review Board of Environmental Health Perspectives.

Since joining the NIEHS, he has been recognized with four NIH Merit Awards, the NIH Director's Award, as well as the Society of Toxicology's Leading Edge in Basic Science Award at the 2010 SOT Annual Meeting.

Selected Publications

  1. Bushel PR, Fannin RD, Gerrish K, Watkins PB, Paules RS. Blood gene expression profiling of an early acetaminophen response. JAMA 2016 ():-. [Abstract]
  2. Fannin RD, Gerrish K, Sieber SO, Bushel PR, Watkins PB, Paules RS. Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clinical pharmacology and therapeutics 2016 99(4):432-441. [Abstract]
  3. Merrick BA, Paules RS and Tice RR. Intersection of Toxicogenomics and High Throughput Screening in the Tox21 Program. (2015). An NIEHS Perspective. Int. J. Biotechnology 14(1):7-27. [Abstract]
  4. Cui Y, Palii SS, Innes CL, Paules RS. Depletion of ATR selectively sensitizes ATM-deficient human mammary epithelial cells to ionizing radiation and DNA-damaging agents. Cell cycle (Georgetown, Tex.) 2014 13(22):3541-3550. [Abstract]
  5. Wang C, Gong B, Bushel PR, Thierry-Mieg J, Thierry-Mieg D, Xu J, Fang H, Hong H, Shen J, Su Z, Meehan J, Li X, Yang L, Li H, Łabaj PP, Kreil DP, Megherbi D, Gaj S, Caiment F, van Delft J, Kleinjans J, Scherer A, Devanarayan V, Wang J, Yang Y, Qian HR, Lancashire LJ, Bessarabova M, Nikolsky Y, Furlanello C, Chierici M, Albanese D, Jurman G, Riccadonna S, Filosi M, Visintainer R, Zhang KK, Li J, Hsieh JH, Svoboda DL, Fuscoe JC, Deng Y, Shi L, Paules RS, Auerbach SS, Tong W5. The concordance between RNA-seq and microarray data depends on chemical treatment and transcript abundance. Nature Biotechnology 2014 32(9):926-932. [Abstract]
  6. Zhang L, Simpson DA, Innes CL, Chou J, Bushel PR, Paules RS, Kaufmann WK, Zhou T. Gene expression signatures but not cell cycle checkpoint functions distinguish AT carriers from normal individuals. Physiological genomics 2013 45(19):907-916.
    [Abstract]
  7. Hesse JE, Liu L, Innes CL, Cui Y, Palii SS, Paules RS. 2013. Genome-Wide Small RNA Sequencing and Gene Expression Analysis Reveals a microRNA Profile of Cancer Susceptibility in ATM-Deficient Human Mammary Epithelial Cells. PloS One,  8(5):e64779. [Abstract]
  8. Innes, C.L., J.E. Hesse, S.S. Palii, B.A. Helmink, A.J. Holub, B.P. Sleckman and R.S. Paules. 2013. DNA damage activates a complex transcriptional response in murine lymphocytes that includes both physiological and cancer-predisposition programs. BMC Genomics, 14(163):online-online. [Abstract]
  9. Palii SS, Cui Y, Innes CL, Paules RS. Dissecting Cellular Responses to Irraditaion Via Targeted Disruptions of the ATM - CHK1 – PP2A Circuit. Cell cycle (Georgetown, Tex.) 2013 12(7):1105-1118. [Abstract]
  10. Innes, C.L., J.E. Hesse, S.S. Palii, B.A. Helmink, A.J. Holub, B.P. Sleckman and R.S. Paules. 2013. DNA damage activates a complex transcriptional response in murine lymphocytes that includes both physiological and cancer-predisposition programs. BMC Genomics, 14(163):online-online. [Abstract]
  11. Vacchi-Suzzi C, Bauer Y, Berridge BR, Bongiovanni S, Gerrish K, Hamadeh HK, Letzkus M, Lyon J, Moggs J, Paules RS, Pognan F, Staedtler F, Vidgeon-Hart MP, Grenet O, Couttet P. 2012. Perturbation of microRNAs in rat heart during chronic doxorubicin treatment. PloS One, 7(7):e40395. [Abstract]
  12. Cui, Y., Huang, Q., Auman, J.T., Knight, B., Jin, X., Blanchard, K.T., Chou, J., Jayadev, S., and Paules, R.S. 2011. Genomic-derived markers for early detection of calcineurin inhibitor immunosuppressant-mediated nephrotoxicity. Toxicological sciences, 124(1):23-34. [Abstract]
  13. Paules, R.S., Aubrecht, J., Corvi, R., Garthoff, B., Kleinjans, J.C. 2011. Moving forward in human cancer risk assessment. Environmental health perspectives, 119(6):739-743. [Abstract]
  14. Shi L, Campbell G, Jones WD, Campagne F, Wen Z, Walker SJ, Su Z, Chu TM, Goodsaid FM, Pusztai L, Shaughnessy JD Jr, Oberthuer A, Thomas RS, Paules RS, Fielden M, Barlogie B, Chen W, Du P, Fischer M, Furlanello C, Gallas BD, Ge X, Megherbi DB, Symmans WF, Wang MD, Zhang J, Bitter H, Brors B, Bushel PR, Bylesjo M, Chen M, Cheng J, Cheng J, Chou J, Davison TS, Delorenzi M, Deng Y, Devanarayan V, Dix DJ, Dopazo J, Dorff KC, Elloumi F, Fan J, Fan S, Fan X, Fang H, Gonzaludo N, Hess KR, Hong H, Huan J, Irizarry RA, Judson R, Juraeva D, Lababidi S, Lambert CG, Li L, Li Y, Li Z, Lin SM, Liu G, Lobenhofer EK, Luo J, Luo W, McCall MN, Nikolsky Y, Pennello GA, Perkins RG, Philip R, Popovici V, Price ND, Qian F, Scherer A, Shi T, Shi W, Sung J, Thierry-Mieg D, Thierry-Mieg J, Thodima V, Trygg J, Vishnuvajjala L, Wang SJ, Wu J, Wu Y, Xie Q, Yousef WA, Zhang L, Zhang X, Zhong S, Zhou Y, Zhu S. The MicroArray Quality Control (MAQC)-II study of common practices for the development and validation of microarray-based predictive models. Nature biotechnology 2010 28(8):827-38.  [Abstract]
  15. Huang, J., Shi, W., Zhang, J., Chou, J.W., Paules, R.S., Gerrish, K., Li, J., Luo, J., Wolfinger, R.D., Bao, W., Chu, T.M., Nikolsky, Y., Nikolskaya, T., Dosymbekov, D., Tsyganova, M.O., Shi, L., Fan, X., Corton, J.C., Chen, M., Cheng, Y., Tong, W., Fang, H., and Bushel, P.R. 2010. Genomic indicators in the blood predict drug-induced liver injury. The pharmacogenomics journal, 10(4):267-277. [Abstract]
  16. Fu, D., Brophy, J., Chan, C.T., Atmore, K.A., 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. Molecular and cellular biology, 30(10):2449-2459. [Abstract]
  17. Cui, Y., and R.S. Paules. 2010. Use of transcriptomics in understanding mechanisms of drug-induced toxicity. Pharmacogenomics, 11(4):573-585. [Abstract]
  18. Bredemeyer, A.L., B.A. Helmink, C.L. Innes, B. Calderon, L.M. McGinnis, G.K. Mahowald, E.J. Gapud, L.M. Walker, J.B. Collins, B.K. Weaver, L. Mandik-Nayak, R.D. Schreiber, P.M. Allen, M.J. May, R.S. Paules, C.H. Bassing, and B.P. Sleckman. 2008. DNA double-strand breaks activate a multi-functional genetic program in developing lymphocytes. Nature, 456 (7223):819-823. [Abstract]
  19. Lobenhofer, E.K., Auman, J.T., Blackshear, P.E., Boorman, G.A., Bushel, P.R., Cunningham, M.L., Fostel, J.M., Gerrish, K., Heinloth, A.N., Irwin, R.D., Malarkey, D.E., Merrick, B.A., Sieber, S.O., Tucker, C.J., Ward, S.M., Wilson, R.E., Hurban, P., Tennant, R.W., and R.S. Paules. 2008. Gene expression response in target organ and whole blood varies as a function of target organ injury phenotype. Genome Biology, 9 (6):R100. [Abstract]
  20. Arlander, S.J.H., Greene, B.T., Innes, C.L., and R.S. Paules. 2008. DNA protein kinase-dependent G2 checkpoint revealed following knockdown of ataxia-telangiectasia mutated in human mammary epithelial cells. Cancer Research, 68 (1):89-97. [Abstract]
  21. Bushel, PR, Heinloth AN, Li J, Huang L, Chou JW, Boorman GA, Malarkey DE, Houle CD, Ward SM, Wilson RE, Fannin RD, Russo MW, Watkins PB, Tennant RW, and R.S. Paules. 2007. Blood gene expression signatures predict exposure levels. Proceedings of the National Academy of Sciences of the United States of America, 104(46):18211-18216. [Abstract]
  22. Heinloth, A.N., R.D. Irwin, G.A. Boorman, P. Nettesheim, R.D. Fannin, S.O. Sieber, M.L. Snell, C. J. Tucker, L. Li, G.S. Travlos, G. Vansant, P.E. Blackshear, R.W. Tennant, M.L. Cunningham, and R.S. Paules. 2004. Gene expression profiling of rat livers reveals indicators of potential adverse effects. Toxicol. Sci., 80, 193-202. [Abstract]
  23. Heinloth, A.N., R.E. Shackelford, C.L. Innes, L. Bennett, L. Li, R.P. Amin, S.O. Sieber, K.G. Flores, P.R. Bushel, and R.S. Paules. 2003. Identification of distinct and common gene expression changes after oxidative stress and gamma and ultraviolet radiation. Mol. Carcinog., 37, 65-82. [Abstract]
  24. Heinloth, A.N., R.E. Shackelford, C.L. Innes, R.P. Amin, S.O. Sieber, K.G. Flores, L. Bennett, P.R. Bushel, and R.S. Paules. 2003. ATM-dependent and ATM-independent gene expression changes in response to oxidative stress, γ-radiation and UV-radiation. Rad. Res., 160, 273-290. [Abstract]
  25. Harding, H.P, Y. Zhang, H. Zeng, I. Novoa, P.D. Lu, B. Popko, R.S. Paules, T. Hettmann, J.M. Leiden, and D. Ron. 2003. An integrated stress response promotes resistance to oxidative stress through amino acid sufficiency. Mol. Cell, 11, 619-633. [Abstract]
  26. Hamadeh, H.K., P.R. Bushel, S. Jayadev, K. Martin, O. DiSorba, S. Sieber, L. Bennett, R. Tennant, R. Stoll, J.C. Barrett, K. Blanchard, R.S. Paules, and C.A. Afshari. 2002. Gene expression analysis reveals chemical-specific profiles. Toxicol. Sci., 67, 219-231. [Abstract]
  27. Wolfinger, R.D., G. Gibson, E.D. Wolfinger, L. Bennett, H. Hamadeh, P. Bushel, C.A. Afshari, and R.S. Paules. 2001. Assessing gene significance from cDNA microarray expression data via mixed models. J. Comp. Biol., 8, 625-637. [Abstract]
  28. Shackelford, R.E, C.L. Innes, S.O. Sieber, A.N. Heinloth, S.A. Leadon, and R.S. Paules. 2001. The ataxia telangiectasia gene product is required for oxidative stress-induced G1 and G2 checkpoint function in human fibroblasts. J. Biol. Chem., 276, 21951-21959. [Abstract]
  29. Shackelford, R.E., W.K. Kaufmann, and R.S. Paules. 2000. Oxidative stress and cell cycle checkpoint function. Free Radic. Biol. Med., 28, 1387-1404. [Abstract]