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Nicole Kleinstreuer, Ph.D.

Headshot of nicole Kleinstreuer
Nicole Kleinstreuer, Ph.D.
Deputy Director - NICEATM
Tel 919-541-7997
nicole.kleinstreuer@nih.gov
530 Davis Dr
Keystone Building
Durham, NC 27713

Nicole C. Kleinstreuer, Ph.D., began her role as Deputy Director of the NTP Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) in 2016. NICEATM conducts data analyses, workshops, independent validation studies, and other activities to assess new, revised, and alternative test methods and strategies and provides support for the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). Kleinstreuer leads NICEATM’s computational toxicology work, helps provide oversight of the NICEATM support contract and assists Warren Casey, Ph.D., in achieving the ICCVAM goals as articulated in the ICCVAM Authorization Act of 2000. She also holds a secondary appointment in the NIEHS Biostatistics and Computational Biology Branch.

Prior to joining NTP, Kleinstreuer worked for Integrated Laboratory Systems, Inc., as a senior staff computational toxicologist and director of the ILS computational toxicology group supporting NICEATM.

Kleinstreuer received her Ph.D. in bioengineering from the University of Canterbury in Christchurch, New Zealand, and B.S. degrees in mathematics and biomedical engineering from the University of North Carolina at Chapel Hill (UNC-CH). Prior to joining ILS, she completed postdoctoral training at the EPA National Center for Computational Toxicology. Kleinstreuer also maintains an adjunct faculty appointment at the Eshelman School of Pharmacy at UNC-CH.

Kleinstreuer’s research focuses on mathematical and computational modeling of biological systems and their susceptibility to perturbations that result in adverse health outcomes. She was a key contributor to a strategy that combines in vitro high throughput assay data with computational models for measuring estrogen receptor bioactivity. This strategy has been accepted by the U.S. Environmental Protection Agency (EPA) as an alternative to three existing Tier 1 tests in the Endocrine Disruptor Screening Program. She leads current efforts to identify alternative testing strategies to screen for androgen receptor bioactivity, as well as international efforts to facilitate regulatory acceptance of skin sensitization test methods that do not use animals. Kleinstreuer also worked closely with the Halifax Project and on associated NIEHS initiatives to identify low-dose chemical effects on cancer hallmark pathways.

Kleinstreuer has won numerous awards including the 2016 F. Clarke Fraser New Investigator Award from the Teratology Society, the 2015 Edward Carney Award for Predictive Toxicology from the American Society for Cellular and Computational Toxicology, an NIEHS group merit award, the Burroughs Wellcome Fund Innovation in Regulatory Science Award, and the B.H. Neumann Prize from the Australian Mathematical Society.

Selected Publications and Reports:

  1. Miller MF, Goodson WH III, Manjili MH, Kleinstreuer N, Bisson WH, Lowe L. Low-Dose Mixture Hypothesis of Carcinogenesis Workshop: Scientific Underpinnings and Research Recommendations. Environmental Health Perspectives 2016 ():-. [Abstract]
  2. Strickland J, Zang Q, Paris M , Lehmann DM, Kleinstreuer N, Allen D, Choksi N, Matheson J, Jacobs A, Casey W. Multivariate models for prediction of human skin sensitization hazard. Journal of applied toxicology: JAT 2016 ():-.  [Abstract]
  3. Kleinstreuer NC, Sullivan K, Allen D, Edwards S, Mendrick DL, Embry M, Matheson J, Rowlands JC, Munn S, Maull E, Casey W. 2016. Adverse Outcome Pathways: From Research to Regulation. Scientific Workshop Report. Regulatory Toxicology & Pharmacology 76:39-50. [Abstract]
  4. Strickland J, Zang Q, Kleinstreuer N, Paris M, Lehmann DM, Choksi N, Matheson J, Jacobs A, Lowit A, Allen D, Casey W. 2016. Integrated Decision Strategies for Skin Sensitization Hazard. Journal of Applied Toxicology doi: 10.1002/jat.3281. [Abstract]
  5. Kleinstreuer NC, Ceger P, Allen D, Strickland J, Chang X, Hamm J, Casey W. (2015) A Curated Database of Rodent Uterotrophic Bioactivity. Environmental Health Perspectives DOI:10.1289/ehp.1510183
  6. Browne P, Judson R, Casey W, Kleinstreuer N, Thomas R. 2015. Screening Chemicals for Estrogen Receptor Bioactivity Using a Computational Model. Environmental Science & Technology. [Abstract]
  7. Goodson W, Lowe L… Kleinstreuer N, et al. (Review article: 139 authors).2015. Assessing the Carcinogenic Potential of Low Dose Exposures to Chemical Mixtures in the Environment: The Challenge Ahead. Carcinogenesis 36 (Suppl 1): S254-S296 doi:10.1093/carcin/bgv039. [Abstract]
  8. Hu Z, Brooks SA, Dormoy V, Hsu C, Hsu H, Lin L, Massfelder T, Rathmell WK, Xia M, Kleinstreuer NC. (2015) Environmental Chemicals in Tumor Angiogenesis. Carcinogenesis 36: S184-S202 [Abstract]
  9. Alves VM, Muratov E, Fourches D, Strickland J, Kleinstreuer NC, Andrade CH, Tropsha A. (2015) Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds. Toxicology and Applied Pharmacology. [Abstract]
  10. Alves VM, Muratov E, Fourches D, Strickland J, Kleinstreuer NC, Andrade CH, Tropsha A. (2015) Predicting chemically-induced skin reactions. Part II: QSAR models of skin permeability and the relationships between skin permeability and skin sensitization. Toxicology and Applied Pharmacology. [Abstract]
  11. McKim J, Goldberg A, Kleinstreuer N, Busquet F, Andersen M. 2015. A Vision of Toxicity Testing in the 21st Century. Applied In Vitro Toxicology 1(1): 10-15. [Abstract]
  12. Chang X, Kleinstreuer NC, Ceger P, Hisieh J-H, Allen D, Casey W. (2014) Application of Reverse Dosimetry to Compare In vitro and In vivo Estrogen Receptor Activity. Applied In Vitro Toxicology, 1(1): 33–44
  13. Kleinstreuer N, Houck K, Yang J, Knudsen T, Dix D, Kavlock R, Richard A, Martin M, Reif D, Judson R, Polokoff M, Berg E. 2014. Phenotypic screening of the ToxCast chemical library to classify toxic and therapeutic mechanisms. Nature Biotechnology 32, 583-591. [Abstract]
    • **Featured in: Westmoreland, C. & Carmichael, P. L. (2014) Chemical safety without animals. Nat Biotech 32, 541-543. [Abstract]
  14. Tal TL, McCollum CW, Harris P, Padilla S, Kleinstreuer NC, Bondesson M, Knudsen TK and Hemmer MK. 2014. Immediate and long-term consequences of vascular toxicity during development using a quantitative vascular disruption assay in zebrafish. Reproductive Toxicology. [Abstract]
  15. Pirone J, Smith M, Kleinstreuer NC, Burns T, Strickland J, Dancik Y, Morris R, Rinckel L, Casey W, Jaworska J. 2014. Open Source Software Implementation of an Integrated Test Strategy for Skin Sensitization Potency Based on a Bayesian Network. ALTEX. [Abstract]
  16. Wambaugh J, Setzer W, Pitruzzello A, Liu J, Reif D, Kleinstreuer N, Ching N, Wang Y, Sipes N, Martin M, Das K, DeWitt J, Strynar M, Judson R, Houck K, Lau C. 2013. Dosimetric Anchoring of In Vivo and In Vitro Studies for Perfluorooctanoate and Perfluorooctanesulfonate. Toxicol Sci136(2):308-27. [Abstract]
  17. Kleinstreuer N, Dix D, Rountree M, Baker N, Sipes N, Reif D, Spencer R, Knudsen T. 2013. A Computational Model Predicting Disruption of Blood Vessel Development. PLoS Comput Biol 9(4): e1002996. [Abstract]
  18. Allard P, Kleinstreuer NC, Knudsen TB, Colaiacovo MP. 2013.  A C. elegans screening platform for the rapid assessment of chemical disruption of germline function. Environ Health Perspect.   [Abstract]
  19. Kleinstreuer N, Dix D, Houck K, Kavlock R, Knudsen T, Martin M, Paul K, Reif D, Crofton K, Hamilton K, Hunter R, Shah I, Judson R. 2013. In vitro Perturbations of Targets in Cancer Hallmark Processes Predict Rodent Chemical Carcinogenesis. Toxicol Sci. Jan; 131(1):40-55. [Abstract]
  20. Kavlock R, Chandler KJ, Dix DJ, Houck KA, Hunter ES, Judson RS, Kleinstreuer NC, Knudsen TB, Martin M, Padilla S, Reif DM, Richard AM, Rotroff D, Sipes NS. 2012. Update on EPA’s ToxCast Program: Providing High Throughput Decision Support Tools for Chemical Risk Management. Chemical Research in Toxicology 25(7):1287-302. [Abstract]
  21. Knudsen TB and Kleinstreuer NC. 2012. Disruption of Embryonic Vascular Development in Predictive Toxicology. Birth Defects Res C Embryo Today, 93(4): p. 312-23. [Abstract]
  22. Padilla S, Corum D, Padnos B, Hunter DL, Beam A, Houck KA, Sipes NS, Kleinstreuer NC, Knudsen T, Dix DJ, Reif DM. 2011. Zebrafish developmental screening of the ToxCastTM Phase I chemical library. Reprod Toxicol. [Abstract]
  23. Kleinstreuer NC, Smith AM, West PR, Conard KR, Fontaine BR, Weir-Hauptman AM, Palmer JA, Knudsen TB, Dix DJ, Donley EL, Cezar GG. 2011. Identifying Developmental Toxicity Pathways for a Subset of ToxCast Chemicals Using Human Embryonic Stem Cells and Metabolomics. Toxicology and Applied Pharmacology. 257(1): 111-21. [Abstract]
  24. Sipes NS, Martin MT, Reif DM, Kleinstreuer NC, Judson RS, Singh AV, Chandler KJ, Dix DJ, Kavlock RJ and Knudsen TB. 2011. Predictive models of prenatal developmental toxicity from ToxCast high-throughput screening data. Toxicol. Sci. 124(1): 109-27. [Abstract]
  25. Kleinstreuer N, Judson R, Reif D, Sipes N, Singh A, Chandler KJ, DeWoskin R, Dix D, Kavlock R and Knudsen T. 2011. Environmental Impact on Vascular Development Predicted by High Throughput Screening (HTS). Environ. Hlth. Perspect. 119(11): 1596-603. [Abstract]
  26. Chandler KJ, Barrier M, Jeffay S, Nichols HP,  Kleinstreuer NC, Singh AV, Reif DM, Sipes NS, Judson RS, Dix DJ, Kavlock R, Hunter ES, and Knudsen TB. 2011. Evaluation of 309 Environmental Chemicals Using a Mouse Embryonic Stem Cell Adherent Cell Differentiation and Cytotoxicity Assay. PLoS One. ; 6(6): e18540. [Abstract]
  27. Knudsen TB, Houck KA, Sipes NS, Singh AV, Judson RS, Martin MT, Weissman A, Kleinstreuer NC, Mortensen HM, Reif DM, Rabinowitz JR, Setzer RW, Richard AM, Dix DJ and Kavlock RJ. 2011. Activity profiles of 309 ToxCast chemicals evaluated across 292 biochemical targets. Toxicology 282: 1-15. [Abstract]