Paul B. Watkins, M.D.

Director, Hamner-UNC Institute for Drug Safety Sciences

pwatkins@thehamner.org
pbwatkins@med.unc.edu
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Education

B.A., physical chemistry, Cornell University, Ithaca, NY, 1975.

M.D., Cornell Medical College, New York, NY, 1979.

Postdoctoral Training:

Internship (Internal Medicine), The New York Hospital - Cornell Medical Center, July 1979 - July 1980.

Residency (Internal Medicine), The New York Hospital - Cornell Medical Center, July 1980 - July 1982.

Clinical Fellow, Medical College of Virginia, McGuire Veterans Administration Medical Center, July 1982 - July 1983.

Research Fellow, NIH Training Grant, Medical College of Virginia, Division of Environmental Medicine and Clinical Toxicology, July 1983 - July 1984.

Fellowship (Gastroenterology/Hepatology), July 1982 - July 1984.

Special Experience:

Admission Ward Physician, Khao-I-Dang Cambodian Refugee Camp, Thailand, April 1982 - July 1982.
             

Research

Paul Watkins, M.D., is the Professor of Medicine, Professor of Toxicology, and Professor of Experimental Therapeutics at The University of North Carolina at Chapel Hill (UNC). As an internationally recognized expert in drug safety, Dr. Watkins has extensive research experience in drug-induced liver injury (DILI), which includes basic investigation in drug metabolism and transport, clinical studies, causation assessment, and regulatory affairs. He has been continuously funded for over 20 years by the National Institutes of Health for basic and translational research, and he is one of the most frequently cited authors in the field of pharmacology.

[Click here to view recorded webinars by Dr. Watkins]

Selected Publications - click to view

Shen, X, Yuan, Z, Mei, J, Zhang, Z, Guo, J, Wu, Z, Wu, J, Zhang, H, Pan, J, Huang, W, Gong, H, Yuan, D, Xiao, P, Wang, Y, Shuai, Y, Lin, S, Pan, Q, Zhou, T, Watkins, PB, Wu, F. Anti-Tuberculosis drug-induced liver injury in Shanghai: Validation of Hy’s Law. In press, Drug Safety, October 2013.

Steuerwald, N, Foureau, D, Norton, HJ, Zhou, J, Parsons, JC, Chalasani, N, Fontana, RJ, Watkins, PB, Lee, WM, Reddy, KR, Stolz, A, Talwalkar, J, Davern, T, Saha, D, Bell, LN, Barnhart, H, Gu, J, Serrano, J, Bonkovsky, HL. Profiles of serum cytokines in acute drug-induced liver injury and their prognostic significance. In press, PLOS ONE, October 2013.

Borlak, J, Chatterji, B, Londhe, KB, Watkins, PB. Serum acute phase reactants hallmark healthy individuals at risk for acetaminophen-induced liver injury. Genome Med 5(9):86, Sept 27 2013. [Epub ahead of print].

Antoine, DJ, Harrill, AH, Watkins, PB, Park, BK. Safety Biomarkers for Drug-induced Liver Injury-Current Status and Future Perspectives. In press, Tox Research, Sept 2013. 

Watkins, PB. Managing the risk of drug-induced liver injury. Clin Pharmacol Ther 94(6):629-631, Dec 2013.  

Davis, M, Boekelheide, K, Boverhof, DR, Eichenbaum, G, Hartung, T, Holsapple, MP, Jones, TW, Richard, AM, Watkins, PB. The New Revolution in Toxicology: The Good, the Bad, and the Ugly. Annals NY Acad Sci 1278(2013): 11- 24, 2013.

Corsini, A, Ganey, P, Ju, C, Kaplowitz, N, Pessayre, D, Roth, R, Watkins, PB, Albassam, M, Liu, B, Stancic, S, Suter, L, Bortolini, M. Current Challenges in Drug-Induced Liver Injury. Drug Saf 35(12):1099-117, Dec 2012.   

Bhattacharya, S, Shoda, LK, Zhang, Q, Woods, C, Howell, BA, Siler, SQ, Woodhead, JL, Yang, Y, McMullen, P, Watkins, PB, Andersen, ME. Modeling drug- and chemical- induced hepatotoxicity with systems biology approaches. Front Physiol 3:462, 2012.

Griffin, LM, Watkins, PB, Perry, CH, St Claire, RL, Brouwer, KL. Combination Lopinavir and Ritonavir Alter Exogenous and Endogenous Bile Acid Disposition in Sandwich-Cultured Rat Hepatocytes. Drug Metab Dispos 41(1):188-96, Jan 2013.

Zhang, L, Bushel, PR, Chou, J, Zhou, T, Watkins, PB. Identification of Identical Transcript Changes in Liver and Whole Blood during Acetaminophen Toxicity. Front Genet 3:162, 2012.

Howell, BA, Yang, Y, Kumar, R, Woodhead, JL, Harrill, AH, Clewell, HJ, Andersen, ME, Siler, SQ, Watkins, PB. 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, Oct 2012. 

Harrill, AH, DeSmet, KD, Wolf, KK, Bridges, AS, Eaddy, JC, Kurtz, CL, Hall, JE, Paine, MF, Tidwell, RR, Watkins, PB. 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, 2012. 

Urban, TJ, Shen, Y, Stolz, A, Chalasani, N, Fontana, RJ, Rochon, J, Dongliang, G, Shianna, KV, Daly, AK, Lucena, MI, Nelson, MR, Molokhia, M, Aithal, GP, Floratos, A, Serrano, J, Bonkovsky, H,  Davern, TJ,  Lee, WM, Navarro, VJ, Talwalkar, JA, Goldstein, DB, Watkins, PB, on behalf of the Drug Induced Liver Injury Network and the International Serious Adverse Events Consortium. Limited contribution of common genetic variants to risk for liver injury due to a variety of drugs. J Pharmacogenet and Genomics 22(11):784-95, 2012.

Winnike, JH, Pediaditakis, P, Wolak, J, McClelland, R, Watkins, PB, Macdonald, JM. Stable Isotope Resolved Metabolomics of Primary Human Hepatocytes Reveals a Stressed Phenotype. In Press, Metabolomics.

Woodhead, JL, Howell, BA, Yang, Y, Harrill, AH, Clewell, HJ, Andersen, ME, Siler, SQ, Watkins, PB. An analysis of N-acetylcysteine treatment for acetaminophen overdose using a systems model of drug-induced liver injury. J Pharmacol Exp Ther 342(2):529-40, 2012.

Urban, TJ, Goldstein, DB, Watkins, PB. Genetic basis of susceptibility to drug-induced liver injury: what have we learned and where do we go from here? Pharmacogenomics 13(7):735-8, 2012.  

Harrill, AH, Roach, J, Fier, I, Eaddy, JS, Kurtz, CL, Antoine, DJ, Spencer, DM, Kishimoto, TK, Pisetsky, DS, Park, BK, Watkins, PB. 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, 2012.

Bell, LN, Vuppalanchi, R, Watkins, PB, Bonkovsky, HL, Serrano, J, Fontana, RJ, Wang, M, Rochon, J, Chalasani, N for the US Drug-Induced Liver Injury Network (DILIN) Research Group. Serum proteomic profiling in patients with drug-induced liver injury. Aliment Pharmacol Ther 35(5):600-612, 2012.

Aithal GP, Watkins PB, Andrade RJ, Larrey D, Molokhia M, Takikawa H, Hunt CM, Wilke RA, Avigan M, Kaplowitz N, Bjornsson E, Daly AK. Case Definition and Phenotype Standardization in Drug-Induced Liver injury. Clin Pharmacol Ther 89(6):806-15, 2011.

Lucena MI, Molokhia M, Shen Y, Urban TJ, Aithal GP, Andrade RJ, Day CP, Ruiz-Cabello F, Donaldson PT, Stephens C, Pirmohamed M, Romero-Gomez M, Navarro JM, Fontana RJ, Miller M, Groome M, Bondon-Guitton E, Conforti A, Stricker BH, Carvajal A, Ibanez L, Yue QY, Eichelbaum M, Floratos A, Pe'er I, Daly MJ, Goldstein DB, Dillon JF, Nelson MR, Watkins PB, Daly AK; Spanish Dili Registry, EUDRAGENE, DILIN, DILIGEN, and International SAEC. Susceptibility to Amoxicillin-Clavulanate-Induced Liver Injury is influenced by Multiple HLA Class I and II Atteles. Gastroenterology 141(1):338-347, July 2011. 

Watkins. PB. Drug Safety sciences and the Bottleneck in Drug Development. Clin Pharmacol Ther 89(6):788-90, 2011.

Robertson, DG, Watkins, PB and Reily, MD. Metabolomics in toxicology: preclinical and clinical applications. Toxicol Sci 120(supp; 1):S146-S170, 2011.   

O’Connell, TM and Watkins, PB. The application of Metabolomics to predict drug-induced liver injury. Clin Pharmacol Ther 88(3):394-9, 2010.

Watkins PB, Desai M, Berkowitz S, Peters G, Horsmans Y, Larrey, D, and Maddrey W.  Evaluation of Drug-Induced Serious Hepatotoxicity (eDISH): Application of This Data Organization Tool to Phase III Clinical Trials of Rivaroxaban after Total Hip or Knee Replacement Surgery. Drug Safety 34 (3)243-252, 2011.  

Stewart JD, Horvath R, Baruffini E, Ferrero I, Bulst S, Watkins PB, Fontana RJ, Day CP, Chinnery PF.  Common POLG genetic variants increase the risk of sodium valproate induced liver injury and failure. Hepatology 52(5):1791-1796, 2010.

Wetmore BA, Brees DJ, Singh R,  Watkins PB, Andersen ME,  Loy J, and Thomas RS. Quantitative Analyses and Transcriptomic Profiling of Circulating mRNAs as Biomarkers of Rat Liver Injury. Hepatology 52(6):2127-2139, 2010.

Winnike JH, Li Z, Wright FA, Macdonald JM, O’Connell TM, and Watkins PB.  Use of Pharmacometabonomics for Early Prediction of Acetaminophen-Induced Hepatotoxicity in Humans. Clin Pharmacol Ther 88(1):45-51, 2010.

Fannin RD, Russo M, O’Connell TM, Gerrish k, Winnike JH, Macdonald J, Newton J, Malik S,  Sieber SO, Parker J, Shah R, Zhou T, Watkins PB, Paules RS.  Acetaminophen dosing of humans results in blood transcriptome and metabolome changes consistent with impaired oxidative phosphorylation. Hepatology 51(1):227-36, 2010.

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 M, Paigen K, Harris C, Contractor T, Wiltshire T, Rusyn I, Threadgill DW.   Mouse Model of the Human Population Reveals that Variants in CD44 Contribute to Acetaminophen-Induced Liver Injury in Humans.  Genome Research (9):1507-15, 2009.

Additional Scientists