Molecular Toxicology & Genomics Group
Alison Harrill, Ph.D.
P.O. Box 12233Mail Drop K2-17Durham, N.C. 27709
Alison Harrill is a scientist in the Molecular Toxicology & Genomics Group within the Biomolecular Screening Branch (BSB) of the National Toxicology Program (NTP).
Harrill is leading efforts toward developing models that incorporate host genetic susceptibility into risk assessment. Genetics plays a key role in metabolism and response to drugs and chemicals, yet the systematic study of population dynamics in toxicity responses is in its infancy and understanding these dynamics may have important implications for human health risk assessment. Her current research includes investigation of population dynamics in response to drugs and chemicals, identification of gene variants that influence toxicity responses, and study of different transcriptional alterations that occur in affected tissues of sensitive versus resistant individuals. These efforts will take aim at reducing uncertainty when extrapolating risk from animal species to human populations.
Prior to joining the NTP, Harrill was an Assistant Professor at the University of Arkansas for Medical Sciences and, prior to her academic tenure, Head of the Translational Pharmacogenetics Laboratory at the Hamner Institutes for Health Sciences. In these roles, she worked to qualify population-based rodent models, such as Diversity Outbred mice, for pharmaceutical safety testing and identification of pharmacogenetics toxicity risk factors that might enable precision medicine strategies. In addition, she has led safety biomarker discovery and qualification efforts that translated from animal species to clinical populations, with particular emphasis on liver and kidney injury biomarkers.
Harrill received her Ph.D. in Toxicology from the University of North Carolina at Chapel Hill and her B.S. in Genetic Engineering from Cedar Crest College (Allentown, PA). She currently serves as a co-chair on the Application of Genomics for Risk Assessment Committee of ILSI/HESI, a member of the Contemporary Concepts in Toxicology Committee within the Society of Toxicology, and an executive committee member within the Toxicology Division of the American Society for Pharmacology and Experimental Therapeutics. She has been honored to receive many awards for her research, most recently: The Best Paper Published in Toxicological Sciences Award (2016) and the Burroughs Wellcome Fund Innovation in Regulatory Sciences Award (2013-2016).
Publications in Pharmacogenomics and Drug and Herbal Safety Assessment (selected)
- Didion JP, Morgan AP, Clayshulte AM, Mcmullan RC, Yadgary L, Petkov PM, Bell TA, Gatti DM, Crowley JJ, Hua K, Aylor DL, Bai L, Calaway M, Chesler EJ, French JE, Geiger TR, Gooch TJ, Garland T Jr, Harrill AH, Hunter K, McMillan L, Holt M, Miller DR, O'Brien DA, Paigen K, Pan W, Rowe LB, Shaw GD, Simecek P, Sullivan PF, Svenson KL, Weinstock GM, Threadgill DW, Pomp D, Churchill GA, Pardo-Manuel de Villena F. (2015) A multi-megabase copy number gain causes maternal transmission ratio distortion on mouse chromosome 2. PLoS Genet 11(2):e1004850. [Abstract]
- Church RJ, Gatti DM, Urban TJ, Long N, Yang X, Shi Q, Eaddy JS, Mosedale M, Ballard S, Churchill GA, Navarro V, Watkins PB, Threadgill DW, Harrill AH. (2015) Sensitivity to hepatotoxicity due to epigallocatechin gallate is affected by genetic background in Diversity Outbred mice. Food Chem Toxicol 76:19-26. [Abstract]
- Mosedale M, Wu H, Kurtz CL, Schmidt SP, Adkins K, Harrill AH. (2014) Dysregulation of protein degradation pathways may mediate the liver injury and phospholipidosis associated with a cationic amphiphilic antibiotic drug. Toxicol Appl Pharmacol 280(10):21-9. [Abstract]
- Harrill AH, Desmet KD, Wolf KK, Bridges AS, Eaddy JS, Kurtz CL, Hall JE, Paine MF, Tidwell RR, Watkins PB. (2012) A mouse diversity panel approach reveals the potential for clinical kidney injury due to DB289 not predicted by classical rodent models. Toxicol Sci 130(2):416-26. [Abstract]
- Harrill AH, Watkins PB, Su S, Ross PK, Harbourt DE, Stylianou IM, Boorman GA, Russo MW, Sackler RS, Harris SC, Smith PC, Tennant R, Bogue MA, Paigen K, Harris C, Contractor T, Wiltshire T, Rusyn I, and Threadgill DW. (2009) Mouse population-guided resequencing reveals that variants in CD44 contribute to acetaminophen-induced liver injury in humans. Genome Res 19(9):1507-15. [Abstract]
Publications in Safety Biomarkers (selected)
- Church RJ, Otieno M, McDuffie JE, Singh B, Sonee M, Hall L, Watkins PB, Ellinger-Ziegelbauer H, Harrill AH. (2016) Beyond miR-122: Identification of MicroRNA Alterations in Blood During a Time Course of Hepatobiliary Injury and Biliary Hyperplasia in Rats. Toxicol Sci 150(1):3-14. [Abstract]
- Shi Q, Yang X, Mattes WB, Mendrick DL, Harrill AH, Beger RD. (2015) Circulating mitochondrial biomarkers for drug-induced liver injury. Biomark Med 9(11):1215-23. [Abstract]
- Harrill AH, Eaddy JS, Rose K, Cullen JM, Ramanathan L, Wanaski S, Collins S, Ho Y, Watkins PB, Lecluyse E. (2014) Liver biomarker and in vitro assessment confirm the hepatic origin of aminotransferase elevations lacking histopathological correlate in beagle dogs treated with GABAA receptor antagonist NP260. Toxicol Appl Pharmacol 277(2): 131-7. [Abstract]
- Thulin P, Nordahl G, Gry M, Yimer G, Aklillu E, Makonnen E, Aderaye G, Lindquist L, Mattsson CM, Ekblom B, Antoine DJ, Park BK, Linder S, Harrill AH, Watkins PB, Glinghammar B, Schuppe-Koistinen I. (2013) Keratin-18 and microRNA-122 complement alanine aminotransferase as novel safety biomarkers for drug-induced liver injury in two human cohorts. Liver Int 34(3):367-78. [Abstract]
- Harrill AH, Roach J, Fier I, Eaddy JS, Kurtz CL, Antoine DJ, Spencer DM, Kishimoto TK, Pisetsky DS, Park BK, Watkins PB. (2012) The effects of heparins on the liver: application of mechanistic serum biomarkers in a randomized study in healthy volunteers. Clin Pharmacol Ther 92(2):214-20. [Abstract]
Publications in Toxicogenomics, Mechanistic Toxicology, and Chemical Safety Assessment (selected)
- Church RJ, Wu H, Mosedale M, Sumner SJ, Pathmasiri W, Kurtz CL, Pletcher MT, Eaddy JS, Pandher K, Singer M, Batheja A, Watkins PB, Adkins K, Harrill AH. (2014) A systems biology approach utilizing a mouse diversity panel identifies genetic differences influencing isoniazid-induced microvesicular steatosis. Toxicol Sci 140(2):481-92. [Abstract]
- Weng Z, Zhou P, Salminen WF, Yang X, Harrill AH, Cao Z, Mattes W, Mendrick DL. (2014) Green tea epigallocatechin gallate binds to and inhibits respiratory complexes in swelling but not normal rat hepatic mitochondria. Biochem Biophys Res Communi 443(3):1097-104. [Abstract]
- Howell BA, Yang Y, Kumar R, Woodhead JL, Harrill AH, Clewell HJ 3rd, Andersen ME, Siler SQ, Watkins PB. (2012) In vitro to in vivo extrapolation and species response comparisons for drug-induced liver injury (DILI) using DILIsym™: a mechanistic, mathematical model of DILI. J Pharmacokinet Pharmacodyn 39(5):527-41. [Abstract]
- Woodhead JL, Howell BA, Yang Y, Harrill AH, Clewell HJ 3rd, Andersen ME, Siler SQ, Watkins PB. (2012) An analysis of N-acetylcysteine treatment for acetaminophen overdose using a systems model of drug-induced liver injury. J Pharmacol Ther 342(2):529-40. [Abstract]
- Harrill AH, Ross PK, Gatti DM, Threadgill DW, and Rusyn I. (2009) Population-Based Discovery of Toxicogenomics Biomarkers for Hepatotoxicity Using a Laboratory Strain Diversity Panel. Toxicol Sci 110(1):235-43. [Abstract]