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Stephen S. Ferguson, Ph.D.

Molecular Toxicology & Genomics Group

Stephen Ferguson, Ph.D.
Stephen S. Ferguson, Ph.D.
Chemist
Tel (919) 541-3799
stephen.ferguson@nih.gov
530 Davis Dr
Keystone Building
Durham, NC 27713

Delivery Instructions
Image Of Xenobiotic sensing receptor hepatic receptor pathways
Xenobiotic sensing receptor hepatic receptor pathways and their downstream sentinel gene targets in response to receptor activation.
Cultures of HepaRG cells form cord-like structures
Cultures of HepaRG cells form cord-like structures of hepatocytes at high seeding densities. CDFDA staining (substrate for the efflux transporter MRP2) demonstrates a polarized epithelium & functional biliary efflux transport.

Stephen S. Ferguson is a scientist in the Molecular Toxicology and Genomics Group within the Biomolecular Screening Branch (BSB) of National Toxicology Program (NTP). Ferguson is also adjunct faculty in the National Toxicology Program Laboratories (NTPL).

In his current role, Ferguson leads NTP efforts to develop and apply more physiologically-relevant in vitro toxicology screening models as part of Phase III of the Tox21 program. Working with the BSB and NTPL, Ferguson’s current research focuses on development of organotypic liver models (96- and 384-well) that better reflect tissue functionality and liver-like xenobiotic metabolism competence. These models are being integrated with data-rich molecular assay platforms (i.e. transcriptomics, metabolomics) and cellular phenotypes (i.e. cell growth, cell viability, stress response) to explore chemical-biological interactions and toxicity potential. Quantitative in vitro to in vivo extrapolation (IVIVE) methods are being developed with these approaches to relate in vitro responses to human/clinical significance for risk assessment.

Prior to joining NTP, Ferguson led the ADME/Tox research program at Life Technologies (formerly CellzDirect) where his group investigated and developed in vitro tools for hepatic biology, drug clearance, and drug-drug interaction pathway research. Ferguson also has a background in contract research management serving for multiple years as a Study Director on numerous non-clinical drug metabolism and pharmacokinetics (DMPK) studies for pharmaceutical research.

Ferguson obtained his B.S. in Chemistry from North Carolina State University followed by a Ph.D. in Chemistry (Bioinorganic focus) with a minor in Biotechnology from North Carolina State University.

 

Recent Publications:

  1. Wetmore BA, Wambaugh JF, Allen B, Ferguson SS, Sochaski MA, Setzer RW, Houck KA, Strope CL, Cantwell K, Judson RS, LeCluyse E, Clewell HJ, Thomas RS, Andersen ME. Toxicol Sci. 2015 Nov;148(1):121-36. doi: 10.1093/toxsci/kfv171. Epub 2015 Aug 6. [Abstract]
  2. Kirman CR, Aylward LL, Wetmore BA, Thomas RS, Sochaski M, Ferguson SS, Csiszar SA, and Olivier J. Applied In Vitro Toxicology. 2015 Jun; 1(2):140-146. doi:10.1089/aivt.2014.0008. Epub 2015 Feb12. [Abstract]
  3. Bonzo JA, Rose K, Freeman K, Deibert E, Amaral K, Ferguson SS, Anderson ME, Witek, RP, LeCluyse EL. Applied In Vitro Toxicology. 2015 Mar; 1(1):45-54. doi:10.1089/aivt.2014.0004. Epub 2015 Feb11. [Abstract]
  4. Richardson VM, Ferguson SS, Sey YM, Devito MJ. Xenobiotica. 2014 May;44(5):391-403. doi:10.3109/00498254.2013.847990. Epub 2013 Oct 31. [Abstract]
  5. Elcombe CR, Peffer RC, Wolf DC, Bailey J, Bars R, Bell D, Cattley RC, Ferguson SS, Geter D, Goetz A, Goodman JI, Hester S, Jacobs A, Omiecinski CJ, Schoeny R, Xie W, Lake BG. Crit Rev Toxicol. Jan; 44(1):64-82. doi: 10.3109/10408444.2013.835786. Epub 2013 Nov 4. Review. [Abstract]
  6. Wetmore BA, Wambaugh JF, Ferguson SS, Li L, Clewell HJ 3rd, Judson RS, Freeman K, Bao W, Sochaski MA, Chu TM, Black MB, Healy E, Allen B, Andersen ME, Wolfinger RD, Thomas RS.  2013.  Relative impact of incorporating pharmacokinetics on predicting in vivo hazard and mode of action from high-throughput in vitro toxicity assays. Toxicol Sci. 132(2):327-346. [Abstract]
  7. Wang D, Li L, Yang H, Ferguson SS, Baer MR, Gartenhaus RB, Wang H. 2013. The constitutive androstane receptor is a novel therapeutic target facilitating cyclophosphamide-based treatment of hematopoietic malignancies. Blood. 121(2):329-38. [Abstract]
  8. Lynch C, Pan Y, Li L, Ferguson SS, Xia M, Swaan PW, Wang H. 2013. Identification of novel activators of constitutive androstane receptor from FDA-approved drugs by integrated computational and biological approaches. Pharm Res. 30(2):489-501. [Abstract]
  9. Smith CM, Nolan CK, Edwards MA, Hatfield JB, Stewart TW, Ferguson SS, Lecluyse EL, Sahi J. J. 2012. A comprehensive evaluation of metabolic activity and intrinsic clearance in suspensions and monolayer cultures of cryopreserved primary human hepatocytes. Pharm Sci. 101(10):3989-4002. [Abstract]
  10. Zhang SY, Surapureddi S, Coulter S, Ferguson SS, Goldstein JA. 2012. Human CYP2C8 is post-transcriptionally regulated by microRNAs 103 and 107 in human liver. Mol Pharmacol. 2012 Jun 20 82(3):529-40. [Abstract]
  11. Black MB, Budinsky RA, Dombkowski A, Cukovic D, LeCluyse EL, Ferguson SS, Thomas RS, Rowlands JC. 2012.Cross-species comparisons of transcriptomic alterations in human and rat primary hepatocytes exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol Sci. 127(1):199-215. [Abstract]
  12. Wetmore BA, Wambaugh JF, Ferguson SS, Sochaski MA, Rotroff DM, Freeman K, Clewell HJ 3rd, Dix DJ, Andersen ME, Houck KA, Allen B, Judson RS, Singh R, Kavlock RJ, Richard AM, Thomas RS. 2012. Integration of dosimetry, exposure and high-throughput screening data in chemical toxicity assessment. Toxicol Sci. 125(1):157-74. [Abstract]
  13. Wang D, Li L, Fuhrman J, Ferguson S, Wang H. 2011.The role of constitutive androstane receptor in oxazaphosphorine-mediated induction of drug-metabolizing enzymes in human hepatocytes. Pharm Res. 28(8):2034-44. [Abstract]
  14. Rana R, Surapureddi S, Kam W, Ferguson S, Goldstein JA. Med25 is required for RNA polymerase II recruitment to specific promoters, thus regulating xenobiotic and lipid metabolism in human liver. Molecular and cellular biology. 2011;31(3):466-81. PMCID: 3028616.
  15. Li Y, Zhou D, Ferguson SS, Dorff P, Simpson TR, Grimm SW. 2010. In vitro assessment of metabolic drug–drug interaction potential of AZD2624, neurokinin-3 receptor antagonist, through cytochrome P(450) enzyme identification, inhibition, and induction studies. Xenobiotica. 40(11):721-9. [Abstract]
  16. Martinez SM, Bradford BU, Soldatow VY, Kosyk O, Sandot A, Witek R, Kaiser R, Stewart T, Amaral K, Freeman K, Black C, LeCluyse EL, Ferguson SS, Rusyn I. 2010. Evaluation of an in vitro toxicogenetic mouse model for hepatotoxicity. Toxicol Appl Pharmacol. 249(3):208-216. [Abstract]
  17. Li L, Hassan HE, Tolson AH, Ferguson SS, Eddington ND, Wang H. 2010. Differential activation of pregnane X receptor and constitutive androstane receptor by buprenorphine in primary human hepatocytes and hepG2 cells. J Pharmacol Exp Ther. 335(3):562-571. [Abstract]
  18. Budinsky RA, LeCluyse EL, Ferguson SS, Rowlands JC, Simon T. 2010. Human and rat primary hepatocyte CYP1A1 and 1A2 induction with 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,7,8-tetrachlorodibenzofuran, and 2,3,4,7,8-pentachlorodibenzofuran. Toxicol Sci. 118(1):224-235. [Abstract]
  19. Rotroff DM, Wetmore BA, Dix DJ, Ferguson SS, Clewell HJ, Houck KA, Lecluyse EL, Andersen ME, Judson RS, Smith CM, Sochaski MA, Kavlock RJ, Boellmann F, Martin MT, Reif DM, Wambaugh JF, Thomas RS. 2010. Incorporating human dosimetry and exposure into high-throughput in vitro toxicity screening. Toxicol Sci. 117(2):348-358. [Abstract]
  20. Li, H, Ferguson, S.S., Wang, H. 2010. Synergistically enhanced CYP2B6 inducibility between a polymorphic mutation in CYP2B6 promoter and pregnane X receptor activation. 2010. Mol Pharmacol. 78(4):704-713. [Abstract]
  21. Rotroff DM,  Beam AL, Dix DJ, , Farmer A, Freeman KM,  Houck KA, Judson RS, LeCluyseEL, Martin MT, Reif DM, Ferguson SS. 2010. Xenobiotic metabolizing enzyme and transporter gene expression in primary cultures of human hepatocytes modulated by ToxCast chemicals.  J. Toxicol.Env. Health B Crit Rev. 13(2-4):329-346. [Abstract]
  22. Rana R, Chen Y, Ferguson S, Kissling GE, Surapureddi S, Goldstein JA. Hepatocyte nuclear factor 4α regulates rifampicin-mediated induction of CYP2C genes in primary cultures of human hepatocytes. Drug Metabolism and Disposition 2010; 38:591-599. [Abstract]

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