Publications and Presentations

2017

Publications

Woodhead, J.L., Watkins, P.B., Howell, B.A., Siler, S.Q., Shoda, L.K.M., 2017. The role of quantitative systems pharmacology modeling in the prediction and explanation of idiosyncratic drug-induced liver injury. Drug Metab. Pharmacokinet. 32, 40–45. doi:10.1016/j.dmpk.2016.11.008

Yang, K., Battista, C., Woodhead, J.L., Stahl, S.H., Mettetal, J.T., Watkins, P.B., Siler, S.Q., Howell, B.A., 2017. Systems pharmacology modeling of drug-induced hyperbilirubinemia: Differentiating hepatotoxicity and inhibition of enzymes/transporters. Clin. Pharmacol. Ther. 101, 501–509. doi:10.1002/cpt.619

Longo, D.M., Generaux, G.T., Howell, B.A., Siler, S.Q., Antoine, D.J., Button, D., Caggiano, A., Eisen, A., Iaci, J., Stanulis, R., Parry, T., Mosedale, M., Watkins, P.B., 2017. Refining Liver Safety Risk Assessment: Application of Mechanistic Modeling and Serum Biomarkers to Cimaglermin alfa (GGF2) Clinical Trials. Clin. Pharmacol. Ther. doi:10.1002/cpt.711

2016

Publications

Woodhead, J.L., Brock, W.J., Roth, S.E., Shoaf, S.E., Brouwer, K.L.R., Church, R., Grammatopoulos, T.N., Stiles, L., Siler, S.Q., Howell, B.A., Mosedale, M., Watkins, P.B., Shoda, L.K.M., 2016. Application of a Mechanistic Model to Evaluate Putative Mechanisms of Tolvaptan Drug-Induced Liver Injury and Identify Patient Susceptibility Factors. Toxicol. Sci. Off. J. Soc. Toxicol. doi:10.1093/toxsci/kfw193 

Longo, D.M. et al. (2016). Elucidating Differences in the Hepatotoxic Potential of Tolcapone and Entacapone With DILIsym(®), a Mechanistic Model of Drug-Induced Liver Injury. CPT Pharmacometrics Syst Pharmacol. 2016 Jan;5(1):31-9. doi: 10.1002/psp4.12053.

Yang, Y., et al. (2016). Sandwich-Cultured Hepatocytes as a Tool to Study Drug Disposition and Drug-Induced Liver Injury. J Pharm Sci. 2016 Feb;105(2):443-59. doi: 10.1016/j.xphs.2015.11.008.

2015

Presentations

Leveraging Pre-clinical and Clinical Data to Predict the Hepatotoxic Potential of New Drug Candidates in Patients using DILIsym®, presented by Dr. Brett Howell, Applied Pharmaceutical Software Conference, 16-September, 2015, Cambridge, Massachusetts.

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Mechanistic Modeling of Drug-Induced Liver Injury: Translation of In Vitro Bile Acid Transporter Inhibition Data to Clinical Hepatotoxicity, presented by Dr. Kyunghee Yang, Annual  Applied Pharmaceutical Analysis Meeting, 14-Sep, 2015. Cambridge, MA, USA.

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Predicting Hepatotoxic Potential of New Drug Candidates in Patients using DILIsym®, presented by Dr. Brett Howell, Japanese Society of Toxicology Annual Meeting, 1-July, 2015, Kanazawa, Japan.

2014

Publications

Yang, Y., et al. (2014). MITOsym®: A Mechanistic, Mathematical Model of Hepatocellular Respiration and Bioenergetics. Pharm Res (12 Dec 2014). [Epub ahead of print].

Woodhead, J.L., et al. (2014). Exploring BSEP inhibition-mediated toxicity with a mechanistic model of drug-induced liver injury. Front Pharmacol. 2014 Nov 7;5:240. doi: 10.3389/fphar.2014.00240. eCollection 2014.

Yang, K., et al. (2014). Systems pharmacology modeling predicts delayed presentation and species differences in bile acid-mediated troglitazone hepatotoxicity. Clin Pharmacol Ther (28 July 2014). doi:10.1038/clpt.2014.158.

Woodhead, J.L., et al. (2014). Mechanistic Modeling Reveals the Critical Knowledge Gaps in Bile Acid-Mediated DILI. CPT Pharmacometrics Syst Pharmacol. 2014 Jul 9;3:e123. doi: 10.1038/psp.2014.21.

Howell, B. A., et al. (2014). Use of a systems model of drug-induced liver injury (DILIsym®) to elucidate the mechanistic differences between acetaminophen and its less-toxic isomer, AMAP, in mice . Toxicol Lett 226(2): 163-172.

Howell, B. A., et al. (2014). A Mechanistic Model of Drug-Induced Liver Injury Aids the Interpretation of Elevated Liver Transaminase Levels in a Phase I Clinical TrialCPT Pharmacometrics Syst Pharmacol 3: e98.


 


Presentations

Use of a mathematical model of drug-induced liver injury to interpret safety biomarker data from early clinical trials for Entolimod, a treatment for life threatening radiation poisoning, presented by Dr. Diane Longo, PKUK 2014 Meeting, 6-Nov, 2014, Bath, UK.

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Systems pharmacology modeling predicts hepatotoxic potential of troglitazone and pioglitazone, presented by Dr. Kyunghee Yang (poster No. 292). 19th North American ISSX meeting/29th JSSX meeting. 19-Oct, 2014, San Francisco, CA.

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Mechanistic modeling of drug-induced liver injury that involves bile acid transport inhibition: a case study with troglitazone, presented by Dr. Kyunghee Yang (invited talk). 12th Annual Discovery on Target: Screening Drug Transporter Proteins, 9-Oct, 2014, Boston, MA.

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Modeling drug- and chemical-induced hepatotoxicity with systems biology approaches, presented by Dr. Brett Howell, Microsomes and Drug Oxidations, 18-May, 2014, Stuttgart, Germany.

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In Silico Models: Where are we Today?, presented by Dr. Brett Howell, Drug-Induced Organ Injury 2014 DIA Conference, 9-May, 2014, Bethesda, MD.

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DILI Biomarkers – in silico Insights, presented by Dr. Brett Howell, FDA/AASLD DILI Conference XIV, 20-Mar, 2014, Bethesda, MD.

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Modeling susceptibility factors: the case study with troglitazone, presented by Dr. Kyunghee Yang (invited talk). FDA DILI Conference XIV, 19-Mar, 2014, Hyattsville, MD.

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Serum Cytokeratin-18 as a Biomarker for Liver Injury?, presented by Dr. Brett Howell, FDA/AASLD DILI Conference XV, 19-Mar, 2015, Bethesda, MD.

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Mechanistic modeling of drug induced liver injury predicts species differences in bile acid-mediated troglitazone hepatotoxicity, presented by Dr. Kyunghee Yang (podium presentation). ASCPT 2014 Annual Meeting. 18-Mar, 2014, Atlanta, GA.


2013

Publications

Shoda, L. K. M., et. al. (2013). Linking physiology to toxicity using DILIsym®, a mechanistic mathematical model of drug-induced liver injury. Biopharm Drug Dispos 35(1): 33-49.


Presentations

DILIsym®, a Mechanistic Model of Drug-Induced Liver Injury, Supports the Interpretation of Elevated Liver Transaminase Levels in a Healthy Volunteer Pooled Safety Population for an Orphan Drug Designed for a Life-Threatening Situation, presented by Dr. Brett Howell (poster), ASCPT Pre-session - Quantitative Systems Pharmacology: An Integrating Framework for Translational Medicine, 5-Mar, 2013, Indianapolis, IN.

The quantitative relationship between intracellular lithocholic acid (LCA) and hepatotoxicity in rat; incorporation into a mechanistic model of drug-induced liver injury (DILI), presented by Kyunghee Yang (poster No. 1059), SOT Annual Meeting and ToxExpo, 12-Mar, 2013, San Antonio, TX. 
Mechanistic modeling illuminates the most important unknowns in bile acid mediated DILI, presented by Dr. Jeffrey Woodhead (poster No. 881), SOT Annual Meeting and ToxExpo, 12-Mar, 2013, San Antonio, TX. 

Computational Exploration of the Role of a Prototypical Damage-Associated Molecular Pattern (DAMP) Molecule in Acetaminophen Hepatotoxicity, presented by Dr. Lisl Shoda (poster), The Role of Drug Metabolism in Immune-Mediated Drug Toxicity: Molecular, Clinical and Mechanistic Aspects (ISSX meeting), 18-Apr, 2013, Cambridge, MA.

Use of a Mechanistic Model of Drug-Induced Liver Injury (DILIsym™) to Support Interpretation of Elevated Liver Transaminase Levels in a Healthy Volunteer Pooled Safety Population for an Orphan Drug Designed for a Life-Threatening Situation, presented by Dr. Brett Howell (poster), American Conference on Pharmacometrics, 14-May, 2013, Fort Lauderdale, FL.

Practical Applications of DILIsym™, a Mechanistic Model of Drug-Induced Liver Injury, presented by Dr. Yuching Yang, Integrated Drug Safety Risk Assessments (World Pharma Congress), 5-Jun, 2013, Philadelphia, PA.

Using the DILIsym™ and MITOsym™ mathematical models to predict in vivo mitochondria-based DILI based on in vitro screening data, presented by Dr. Scott Siler (poster), 246th ACS National Meeting, 10-Sept, 2013, Indianapolis, IN.

Systems biology approaches to yield mechanistic insight from in vitro data, presented by Dr. Brett Howell, In vitro markers and endpoints of hepatotoxicity workshop, 17-Sept, 2013, Liverpool, United Kingdom.

2012

Publications

Bhattacharya, S., et. al. (2012). Modeling drug- and chemical-induced hepatotoxicity with systems biology approaches. F Phys 3(462): 1-18.


Woodhead, J. L., et al. (2012). An analysis of N-acetylcysteine treatment for acetaminophen overdose using a systems model of drug-induced liver injury. J Pharmacol Exp Ther 342(2): 529-540.

Howell, B. A., et al. (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 Phar 39(5): 527-541.


Presentations

Computational Prediction of Liver Toxicity Using the DILIsymTM Model, presented by Dr. Brett Howell, American Chemical Society (ACS) National Meeting, 20-Aug, 2012, Philadelphia, PA.


Impact of Modeling & Simulation in Drug Development-DILIsymTM, presented by Dr. Scott Siler, Rosa World-Wide Webinar, 19-Jun, 2012.


Insights into the Management of Acetaminophen Poisoning from DILIsymTM – An In Silico Model of the Liver, presented by Dr. Brett Howell, American Association for the Study of Liver Diseases Clinical Single Topic Conference, 9-Jun, 2012, Atlanta, GA.


Using the DILIsymTM Model to Understand Mechanisms of Hepatotoxicity, presented by Dr. Scott Siler, World Pharma Congress Drug Safety Summit, 7-Jun, 2012, Philadelphia, PA.


An Analysis of N-Acetylcysteine Treatment for Acetaminophen Overdose Using A Systems Model of Drug-Induced Liver Injury, presented by Dr. Jeffrey Woodhead, Society of Toxicology Annual Meeting, 12-Mar, 2012, San Francisco, CA.

2011

Presentations

DILI-sim: An in silico Approach to Understanding and Predicting Drug-Induced Liver Injury, presented by Dr. Brett Howell, World Pharma Congress Drug Safety Summit, 9-Jun, 2011, Philadelphia, PA.


Applications of a Computational Model for Predicting Drug-Induced Liver Injury (DILI), presented by Dr. Brett Howell, Defense Threat Reduction Agency Monthly Seminar, 7-Mar, 2011, Washington, DC.


Applications of a Computational Model for Predicting Drug-Induced Liver Injury (DILI), presented by Dr. Brett Howell, Society of Toxicology Annual Meeting, 8-Mar, 2011, Washington, DC.


Prediction of Drug-Induced Liver Injury Using a Mechanism-Based Computational Model, presented by Dr. Brett Howell, American Society of Clinical Pharmacology and Therapeutics Annual Meeting, 4-Mar, 2011, Dallas, TX.

2010

Presentations

DILI-Sim: A Mechanistically Based Computational Model for Predicting Drug Induced Liver Injury (DILI), presented by Dr. Brett Howell, American Institute of Chemical Engineers Annual Meeting, 7-Nov, 2010, Salt Lake City, UT.


Biosimulation of Drug-Induced Liver Injury, presented by Dr. Harvey Clewell, American Chemistry Society National Meeting, 22-Aug, 2010, Boston, MA.


Biosimulation of Acetaminophen-Induced Liver Injury Using the Entelos PhysioLab® Platform, presented by Dr. Harvey Clewell, American Association for the Study of Liver Diseases, 24-Mar, 2010, Silver Spring, MD.

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