Philip Hewitt

I am still energized to improve our understanding of mechanisms of toxicity, and how we can improve our early predicitvity of human safety liabilities.

Perspective

I originally arrived at our company from San Francisco as a short term step before heading back to the UK! But, I have been enormously lucky over the years - and quickly realized that I really love my job and don't want to leave!

I have spent 20 years establishing and managing a molecular toxicology group in the Non-Clinical Safety (NCS) department. This has included the establishment of new labs, recruitment of personnel, and initiating tissue culture and molecular biology techniques. The current group includes many students, both undergraduates and post-graduates. We have been involved in multiple large EU  projects over the past 15 years and collaborated with many other experts in the safety field. 

After 20 years in the company, I am still energized to improve our understanding of mechanisms of toxicity, and how we can improve our early predicitvity of human safety liabilities. We need to reduce (and finally replace) animals in pharmaceutical research, but also be sure that we are progressing the right drug candidate in to the clinics. To this aim over the last 9 months I have been very active in pushing the implementation of a new Innovative Safety Lab within NCS - with a major focus on innovative, translational cell models. This currently includes assessing 3D systems, organ-on-a-chip (OoaC) technologies, as well as the potential of 3D bioprinting. In the future the embedding of micro biosensors into these systems is of high interest and we are currently discussing with our Life Science colleagues, Innovation Centre and external partners on how to achieve this. Another important topic is the source of cells we use - and to this end we are actively working with pluripotent stem cells, which theoretically can be differentiated in to all the different cell types of the body. But there is still along way to go.

These aspirations are now starting to bear fruit, with clear support from management - which maybe has not always been the case over the past 5 years. Acquiring sufficient funding, technical expertise and personnel is still a challenge. But a recent OoaC workshop at our company clearly shows the huge excitement across multiple functions within our company.

It is clear that replacement of animals will not happen in the near future - BUT if we can reduce the numbers used (e.g., because of better understanding of mechanisms of toxicity; novel biomarkers that can increase the sensitivity / predicitivity of an animal model) or refine current studies (e.g., reduce the degree of animal suffering by choosing only candidates that have been shown in vitro NOT to cause organ toxicity), we are moving in the right direction. And with the rapid development of MPS/organ-on-a-chip technologies I see this as an inevitability in the coming years. And importantly, as Merck KGaA, Darmstadt, Germany is such a diverse company, we can be at the fore-front of these advances.

I am still energized to improve our understanding of mechanisms of toxicity, and how we can improve our early predicitvity of human safety liabilities.

Philip Hewitt

Head of early Investigative Toxicology.

Profile

Joined Merck KGaA, Darmstadt, Germany: 1998

Key research fields and topics:

  • Toxicology: in vitro; alternative methods; 3Rs
  • Understanding mechanism of toxicity relating to liver and intestine
  • 3D Microphysiological systems and organ-on-a-chip technologies
  • Use of pluripotent stem cells in research
  • Novel biomarkers for organ specific toxicity assessment
  • Potential of micro biosensors to improve animal studies and implementation in to 3D in vitro systems

Prizes and awards:

PhD student awards for my lab:- 

  • Nadine Zidek; Gerhard-Zbinden Young Scientist award at Eurotox 2005
  • Jens Hrach; Young Scientist award at Eurotox 2007
  • Kathleen Bohme; Young Scientist award at Eurotox 2009
  • Birthe Lauer; Bo Holmstedt Poster award at Eurotox 2010
  • Germaine Truisi; Young Scientist award at Eurotox 2012

CV & Scientific activities

CV: Education

CV: Education

CV: Professional Career

CV: Professional Career

Memberships

Memberships

References

Publications

  • Physiological and toxicological evaluation of advanced 3D liver models for toxicological profiling in the pharmaceutical industryVolume 4, Number 1, 2018. APPLIED IN VITRO TOXICOLOGY
  • Long-Lasting and Fast-Acting in Vivo Efficacious Antiplasmodial Azepanylcarbazole Amino Alcohol.  Nada Abla, Sridevi Bashyam, Susan A. Charman, Béatrice Greco, Philip Hewitt, Maria Belén Jiménez-Díaz, Kasiram Katneni, Holger Kubas, Didier Picard, Yuvaraj Sambandan, Laura Sanz, Dennis Smith, Tai Wang, Paul Willis, Sergio Wittlin, and Thomas Spangenberg. Med Chem Lett. 2017 Nov 28;8(12):1304-1308
  • Test systems in drug discovery for hazard identification and risk assessment of human drug-induced liver injury. Weaver RJ, Betts C, Blomme EAG, Gerets HHJ, Gjervig Jensen K, Hewitt PG, Juhila S, Labbe G, Liguori MJ, Mesens N, Ogese MO, Persson M, Snoeys J, Stevens JL, Walker T, Park BK.Expert Opin Drug Metab Toxicol. 2017 Jul;13(7):767-782
  • Investigative Toxicology review paper: under review at Nature Reviews Drug Discovery 2017. 
  • Drug mechanism predominates over toxicity mechanisms in drug induced gene expression. Ying-Ying Jiang, Tobias C. Fuchs, Kristina Erdeljan, Bojana Lazerevic, Philip Hewitt, Gordana Apic & Robert . Russell. Under review at ALTEX
  • "Assessing the mechanism and therapeutic potential of modulators of the human mediator complex-associated protein kinases" (2016). eLIFE, Dec 9;5
  • Key challenges and opportunities associated with the use of in vitro models to detect human DILI: integrated risk assessment and mitigation plans (2016). Franck A. Atienzar, Eric A. G. Blomme, Minjun Chen, Philip Hewit, Gerry Kenna, Gilles Labbe, Frederic Moulin, Francois Pognan, Adrian Roth, Laura Suter-Dick, Okechukwu Ukairo, Richard Weaver, Yvonne Will and Donna Dambach. Journal of Biomedical Research International, Epub September 5, 2016
  • Toxicogenomics in preclinical development. Tobias C Fuchs, Germaine L Truisi, Philip G Hewitt - to be published in "A Comprehensive Guide to Toxicology in Preclinical Drug Development. Book Chapter accepted for publication:
  • In-house validation of a cell-based test system for the prediction of human neurotoxicity in early preclinical drug development. Alexander Kunz*, Johanna Sebbel, Christoph van Amsterdam. Philip Hewitt. In preparation
  • A multi-center assessment of the use of primary human hepatocytes, HepG2, HepaRG and Upcyte cells, with basic measures of cell health, as single cell models of acute hepatotoxicity. Rowena Sison-Young, Volker M. Lauschke, Esther Johann, Eliane Alexandre, Sebastien Antherieu, Hélène Aerts, Helga Gerets, Gilles Labbe, Christopher Schofield, Simone Stahl, Cerys Lovatt, Julie Holder, Lysiane Richert, Neil Kitteringham, Robert Jones, Mohamed Elmasry, Richard Weaver, Phil Hewitt, Magnus Ingelman-Sundberg, Chris Goldring and Kevin Park. Toxicological Sciences, online 26th June 2016
  • Evidence-based selection of training compounds for use in the mechanism-based integrated prediction of drug-induced liver injury in man. (2016) Archioves of Toxicology, Dec, 90(12), 2979-3003
  • Comparative Proteomic Characterization of 4 Human Liver-Derived Single Cell Culture Models Reveals Significant Variation in the Capacity for Drug Disposition, Bioactivation, and Detoxication. Sison-Young RL, Mitsa D, Jenkins RE, Mottram D, Alexandre E, Richert L, Aerts H, Weaver RJ, Jones RP, Johann E, Hewitt PG, Ingelman-Sundberg M, Goldring CE, Kitteringham NR, Park BK. Toxicol Sci. 2015;147(2):412-24.
  • Nephron Toxicity Profiling via Untargeted Metabolome Analysis Employing a High Performance Liquid Chromatography-Mass Spectrometry-based Experimental and Computational Pipeline. Ranninger C, Rurik M, Limonciel A, Ruzek S, Reischl R, Wilmes A, Jennings P, Hewitt P, Dekant W, Kohlbacher O, Huber CG. J Biol Chem. 2015;290(31):19121-32
  • Drug biokinetic and toxicity assessments in rat and human primary hepatocytes and HepaRG cells within the EU-funded Predict-IV project. Mueller SO, Guillouzo A, Hewitt PG, Richert L. Toxicol In Vitro. 2015;30:19-26.
  • Kinetics and dynamics of cyclosporine A in three hepatic cell culture systems. Bellwon P, Truisi GL, Bois FY, Wilmes A, Schmidt T, Savary CC, Parmentier C, Hewitt PG, Schmal O, Josse R, Richert L, Guillouzo A, Mueller SO, Jennings P, Testai E, Dekant W. Toxicol In Vitro. 2015;30:62-78.
  • Transcriptomics hit the target: Monitoring of ligand-activated and stress response pathways for chemical testing. Limonciel A, Mönks K, Stanzel S, Truisi GL, Parmentier C, Aschauer L, Wilmes A, Richert L, Hewitt P, Mueller SO, Lukas A, Kopp-Schneider A, Leonard MO, Jennings P. Toxicol In Vitro. 2015
  • Understanding the biokinetics of ibuprofen after single and repeated treatments in rat and human in vitro liver cell systems. Truisi GL, Consiglio ED, Parmentier C, Savary CC, Pomponio G, Bois F, Lauer B, Jossé R, Hewitt PG, Mueller SO, Richert L, Guillouzo A, Testai E. Toxicol Lett. 2015
  • Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Savary CC, Jiang X, Aubry M, Jossé R, Kopp-Schneider A, Hewitt P, Guillouzo A. Toxicol In Vitro. 2015
  • Development of an in vitro renal epithelial disease state model for xenobiotic toxicity testing.. Crean D, Bellwon P, Aschauer L, Limonciel A, Moenks K, Hewitt P, Schmidt T, Herrgen K, Dekant W, Lukas A, Bois F, Wilmes A, Jennings P, Leonard MO. Toxicol In Vitro. 2014
  • Biokinetics of chlorpromazine in primary rat and human hepatocytes and human HepaRG cells after repeated exposure. Broeders JJ, Parmentier C, Truisi GL, Jossé R, Alexandre E, Savary CC, Hewitt PG, Mueller SO, Guillouzo A, Richert L, van Eijkeren JC, Hermens JL, Blaauboer BJ. Toxicol In Vitro. 2014
  • Application of RNA interference to improve mechanistic understanding of omics responses to a hepatotoxic drug in primary rat hepatocytes. Adler M, Leich E, Ellinger-Ziegelbauer H, Hewitt P, Dekant W, Rosenwald A, Mally A. Toxicology. 2014
  • Application of RPTEC/TERT1 cells for investigation of repeat dose nephrotoxicity: A transcriptomic study. Aschauer L, Limonciel A, Wilmes A, Stanzel S, Kopp-Schneider A, Hewitt P, Lukas A, Leonard MO, Pfaller W, Jennings P Toxicol In Vitro. 2014
  • Mechanism of cisplatin proximal tubule toxicity revealed by integrating transcriptomics, proteomics, metabolomics and biokinetics. Wilmes A, Bielow C, Ranninger C, Bellwon P, Aschauer L, Limonciel A, Chassaigne H, Kristl T, Aiche S, Huber CG, Guillou C, Hewitt P, Leonard MO, Dekant W, Bois F, Jennings P Toxicol In Vitro. 2014
  • Interleukin-19 as a translational indicator of renal injury. Jennings P, Crean D, Aschauer L, Limonciel A, Moenks K, Kern G, Hewitt P, Lhotta K, Lukas A, Wilmes A, Leonard MO. Arch Toxicology, 2014
  • A rat toxicogenomics study with the Calcium Sensitizer EMD 82571 reveals a pleiotropic cause in teratogenicity. Phil G. Hewitt, Prafull Kumar Singh, Arun Kumar, Carsten Gnewuch, Gerhard Liebisch, Gerd Schmitz and Juergen Borlak. Submitted to Toxicological Sciences
  • Genomic applications for assessing toxicities of liver and kidney injury. P Hewitt and E Johann. To be published in Predictive Toxicology from Vision to Reality. Eds.: Friedlieb Pfannkuch and Laura Suter-Dick, Wiley-VCH Publisher
  • Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME. Godoy et al. (2013). Arch Toxicol. 2013 Aug;87(8):1315-530
  • Transcriptomic hepatotoxicity signature of chlorpromazine after short- and long-term exposure in primary human sandwich cultures. Parmentier C, Truisi GL, Moenks K, Stanzel S, Lukas A, Kopp-Schneider A, Alexandre E, Hewitt PG, Mueller SO, Richert L. Drug Metab Dispos. 2013 Oct;41(10):
  • Application of integrated transcriptomic, proteomic and metabolomic profiling for the delineation of mechanisms of drug induced cell stress. Wilmes A, Limonciel A, Aschauer L, Moenks K, Bielow C, Leonard MO, Hamon J, Carpi D, Ruzek S, Handler A, Schmal O, Herrgen K, Bellwon P, Burek C, Truisi GL, Hewitt P, Di Consiglio E, Testai E, Blaauboer BJ, Guillou C, Huber CG, Lukas A, Pfaller W, Mueller SO, Bois FY, Dekant W, Jennings P. J Proteomics. 2013 Feb 21;79:180-94
  • Delineation of the key aspects in the regulation of epithelial monolayer formation" by Lydia Aschauer, Leonhard Gruber, Walter Pfaller, Alice Limonciel, Toby Athersuch, Rachel Cavill, Abdulhameed Khan, Gerhard Gstraunthaler, Johannes Grillari, Regina Grillari, Philip Hewitt, Martin Leonard, Anja Wilmes, and Paul Jennings. Mol Cell Biol. 2013 Jul;33(13):2535-50
  • An Exploratory Evaluation of the Utility of Transcriptional and Urinary Kidney Injury Biomarkers for the Prediction of Aristolochic Acid-Induced Renal Injury in Male Rats.. Tobias Christian Fuchs; Angela Mally; Assaf Wool; Merav Beiman; Philip Hewitt. Vet Pathol. 2013 Aug 2. [Epub ahead of print]
  • Toxicology Overview. P Hewitt, C Schuetz, T Wahl and H Maibach. To be published in Cosmaceuticals – Drugs vs Cosmetics, 3rd Edition. To be published 2012
  • Toxicogenomics. C. S. Schmitt and P. Hewitt. In Drug Discovery and Evaluation: Safety Assay (D. Mayer ed). To be published 2012
  • Toxicogenomics in preclinical development. In: A comprehensive guide to Toxicology in preclinical drug development. Tobias C Fuchs, Germaine L Truisi, Philip G Hewitt. Elsevier (in press)
  • Evaluation of Novel Acute Urinary Rat Kidney Toxicity Biomarker for Subacute Toxicity Studies in Preclinical Trials. T. Fuchs, K Frick, B Emde, S Czasch, F Von Landenberg and P Hewitt. Toxicol Pathol. 2012 Oct;40(7):1031-48(2012)
  • A Sposny and P Hewitt. SELDI-TOF Mass Spectrometry-Based protein profiling of tissue samples for toxicological studies. In: Methods in Molecular Biology; Springer Sciences and Business (2012)
  • In vitro systems in pharmacology, toxicology and basic research: Review article submitted to Xenobiotica, 2012
  • Development of a pharmaceutical hepatotoxicity biomarker panel using a discovery to targeted proteomics approach. Ben C. Collins, Christine Miller, Alexandra Sposny, Phillip Hewitt, Martin Wells, William M. Gallagher, and Stephen R. Pennington. Mol Cell Proteomics. 2012 Aug;11(8):394-41
  • Systemic Toxicity. G Truisi and P Hewitt; In Dermatotoxicity, Marzulli and Maibach (eds) 8th Edition, Informa Healtghcare. To be published in 2012
  • Cryopreserved HepaRG Cells for Multiparameter High Content Analysis. Aarati Ranade, Simone Graeber, Philip Hewitt, Stefan O. Mueller, Jeff Till, Andrew J. Ball. Poster SOT 2012
  • Preclinical perspective of urinary biomarkers for the detection of nephrotoxicity – What we know and what we need to know. Tobias C. Fuchs and Philip Hewitt. Biomarkers Med. (Future Medicine) 5 (6), 763-779 (2011)
  • Biomarkers for Drug-induced Renal Damage and Nephrotoxicity - An Overview for Applied Toxicology. Tobias C. Fuchs and Philip Hewitt. The AAPS Journal (2011), online 04.10.11
  • Development of an in vitro liver toxicity prediction model based on longer term primary rat hepatocyte culture. J. Hrach, S.O. Mueller, P. Hewitt. Toxicology Letters, 2011, 206, 189-196
  • Poster Tobias Eurotox 2011 Establishment of an in-vitro screening assay for the early detection of nephrotoxicity. Tobias C. Fuchs, Birthe Lauer and Philip Hewitt
  • Poster Birthe Eurotox 2011
  • Retrospective gene expression analysis using formalin-fixed tissue blocks from toxicological studies. F. v. Landenberg, S.O. Mueller and P. Hewitt, C.S. Schmitt. Poster and oral presentation at SOT 2011
  • State-of-the-art detection of nephrotoxicity by urinary protein biomarkers. T. C Fuchs, B. Emde, S. Czasch, F. v Landenberg, P. Hewitt. Poster and oral presentation at SOT 2011
  • Genomic Profiling uncovers a molecular pattern for toxicological characterisation of mutagens and promutagens in vitro. Boehme K, Dietz Y, Hewitt P, Mueller S. Tox. Sci., 2011, 122(1) 185-197
  • Mechanistic Investigation of EMD335823s Hepatotoxicity using Multiple Omics Profiling Technologies. Hewitt PG, Sposny A, Schmitt C, in “Handbook of Systems Toxicology”, ed DA Casciano and SC Sahu, Chichester UK: Wiley and Sons Ltd, 389-406, 2011
  • Cross-study and cross-omics comparisons of three nephrotoxic compounds reveal mechanistic insights and new candidate biomarkers. Matheis KA, Com E, Gautier JC, Guerreiro N, Brandenburg A, Gmuender H, Sposny A, Hewitt P, Amberg A, Boernsen O, Riefke B, Hoffmann D, Mally A, Kalkuhl A, Suter L, Dieterle F, Staedtler F. Toxicol Appl Pharmacol. 2010 Nov 21. [Epub ahead of print]
  • The enhanced value of combining conventional and "omics" analyses in early assessment of drug-induced hepatobiliary injury. Ellinger-Ziegelbauer H, Adler M, Amberg A, Brandenburg A, Callanan JJ, Connor S, Fountoulakis M, Gmuender H, Gruhler A, Hewitt P, Hodson M, Matheis KA, McCarthy D, Raschke M, Riefke B, Schmitt CS, Sieber M, Sposny A, Suter L, Sweatman B, Mally A. Toxicol Appl Pharmacol. 2010 Oct 1. [Epub ahead of print]
  • Evaluation of a urinary kidney biomarker panel in rat models of acute and subchronic nephrotoxicity. Hoffmann D, Fuchs TC, Henzler T, Matheis KA, Herget T, Dekant W, Hewitt P, Mally A. Toxicology. 2010 Nov 9;277(1-3):49-58. Epub 2010 Sep 9.
  • Activation of P53 in HepG2 cells as surrogate to detect mutagens and promutagens in vitro. Boehme K, Dietz Y, Hewitt P, Mueller SO. Toxicol Lett. 2010 Oct 5;198(2):272-81. Epub 2010 Jul 22.
  • Assessment of candidate biomarkers of drug-induced hepatobiliary injury in preclinical toxicity studies. Adler M, Hoffmann D, Ellinger-Ziegelbauer H, Hewitt P, Matheis K, Mulrane L, Gallagher WM, Callanan JJ, Suter L, Fountoulakis MM, Dekant W, Mally A. Toxicol Lett. 2010 Jun 16;196(1):1-11. Epub 2010 Apr 1
  • Hoffmann, D., Adler, M., Vaidya, V., Rached, E., Mulrane, L., Gallagher, W. M., Callanan, J. J., Gautier, J. C., Matheis, K., Staedtler, F., Dieterle, F., Brandenburg, A., Sposny, A., Hewitt, P., Ellinger-Ziegelbauer, H., Bonventre, J. V., Dekant, W. and Mally, A. (2010). Performance of novel kidney biomarkers in preclinical toxicity studies. Toxicol Sci 116, 8-22.
  • Use of SELDI MS to discover and identify potential biomarkers of toxicity in InnoMed PredTox: a multi-site, multi-compound study.. Collins BC, Sposny A, McCarthy D, Brandenburg A, Woodbury R, Pennington SR, Gautier JC, Hewitt P, Gallagher WM. Proteomics. 2010 Apr;10(8):1592-608
  • Development of an in vitro liver toxicity prediction model based on longer term primary rat hepatocyte cultures. J Hrach and P Hewitt (2009). Toxicology Letters, 189S, S92
  • Toxicogenomics applications: Liver toxicity of a PTP-1B inhibitor drug candidate. P Yu, V Barbie, F Goretta, M Ardizzone, S Peano and P Hewitt (2009). Toxicology Letters, 189S, S89
  • Genomics and its surrounding technologies. Looking to the future of toxicogenomics. C Schmitt and P G Hewitt, (2009). Toxicology Letters, 189S, S30
  • A novel in vitro system for the toxicological evaluation of genotoxic compounds. K Boehme, Y Dietz, P G Hewitt, SO Mueller (2009). Toxicology Letters, 189S, S90
  • Evaluation of urinary kidney biomarkers in rat models of acute and subchronic nephrotoxicity. D Hoffmann, T Henzler, T Herget, S Callahan, W Dekant, P Hewitt, A Mally (2009). Toxicology Letters, 189S, S152
  • Assessment of candidate biomarkers of drug induced liver injury in preclinical toxicity studies. M Adler, D Hoffmann, H Ellinger, P Hewitt, K Matheis, L Mulrane, WM Gallagher, L Suter-Dick, MM Fountoulakis, W Dekant and A Mally (2009). Toxicology Letters, 189S, S152 
  • Value of new biomarkers for safety testing in drug development. T Herget and P Hewitt (2009). Expert Review of Molecular Diagnostics, 9(6), 531-536 
  • Gene expression profiling in toxicological studies using FFPE tissues. C Schmitt, A Walijew, P Hewitt and JH Harleman. Experimental and Toxicological Pathology, (2009), 61, 387-413
  • Serum-free collagen sandwich cultures of adult rat hepatocytes maintain liver-like properties long term: A valuable model for in vitro toxicity and drug-drug interaction studies. Tuschl G, Hrach J, Walter Y, Hewitt PG and Mueller SO. Chem Biol Interact. 2009 May 29
  • Protein extraction from FFPE tissues for toxicological evaluation. GL Truisi, CS Schmitt and PG Hewitt. Naunyn-Schmiedeberg's Archives of Pharmacology, Volume 379, Supplement 1 (2009)
  • Toxicogenomics in drug safety assessment. Hewitt P and Walijew A. Pharmacogenomics (2008) 9(4):379-82
  • Pathway analysis tools and toxicogenomics reference databases for risk assessment. Ganter B, Zidek N, Hewitt P, Müller D, Vladimirova A. Pharmacogenomics (2008) 9(1):35-54
  • In vivo and in vitro mechanistic analyses of lipopolysaccharide (LPS)-induced hepatotoxicity demonstrate similar toxicity patterns. B Ganter, N Zidek, P Hewitt, D Mueller, DL Abramovitz, DN Halbert and A Vladimirova. Toxicological Sciences (suppl), 102 (1), 1123, 2008 
  • Gene expression profiling in toxicological studies using FFPE tissues. P Hewitt and C Schmitt. Toxicological Sciences (suppl), 102 (1), 1570, 2008
  • Genomics and proteomics analysis of cultured primary rat hepatocytes. J Beigel, K Fella, P-J Kramer M Kroeger and P G Hewitt. Toxicology in Vitro. (2008) 22(1):171-81
  • Development of an in vitro liver toxicity prediction model based on long term primary hepatocyte cell culture. J Hrach and P Hewitt. Toxicology Letters, S32-S246 (2008)
  • Gene expression profiling in toxicological studies: a comparison between FFPE and fresh frozen liver tissue. C Schmitt, A Walijew, JH Harleman and P Hewitt. Naunyn-Schmiedeberg's Archives of Pharmacology, Volume 377, Supplement 1 (2008)
  • Long-term cell culture models for the analysis of hepatotoxicity in vitro. G Tuschl, J Hrach, L Richert, C Chesne, PG Hewitt and SO Mueller. Toxicology Letters, S1-S240 (2007)
  • Affymetrix and Illumina, a rat toxicogenomic based interplatform comparison. J Hrach, A von Heydebreck, P Hewitt. Toxicology Letters, S1-S240 (2007)
  • Acute hepatotoxicity: A predictive model based on focussed Illumina microarrays. N Zidek, P-J. Kramer, PG. Hewitt. Toxicological Sciences, (2007) 99(1):289-302
  • Functional Characterisation of Long-term Primary Rat Hepatocyte Cultures as a Model for Repeat-Dose Toxicity. G Tuschl, J Hrach, PG Hewitt, and SO Mueller. Naunyn-Schmiedeberg’s Archives of Pharmacology (2007), Vol 375(1), 481
  • Comparison of gene expression changes caused by selective and mixed PPAR-agonists in primary human hepatocytes in vitro. H Hrach, P-J Kramer and P G Hewitt. Archives of Pharmacology, 372 (S1), 2006
  • Gene expression profiling delineates species-specific action of mixed and selective PPAR agonists. Tuschl, G., Heydebreck, A. v., Hewitt, P. G. and Mueller, S. O. Archives of Pharmacology 372 (Suppl.1), 128, 2006
  • Early characterisation of hepatotoxicants by custom made illumine microarrays. N Zidek, P-J Kramer and P G Hewitt. Archives of Pharmacology, 372 (S1), 2006
  • Early characterisation of hepatotoxicants by focused illumina microarray. N Zidek, P-J Kramer and P G Hewitt. Toxicology Letters, 164S, S295, 2006
  • Toxicogenomics and proteomics. P Hewitt and M Kroeger. In: Drug Discovery and Evaluation: Safety and Pharmacokinetic Assays. H G Vogel (ed). Springer-Verlag, 2006
  • Establishment of Illumina custom arrays for hepatotoxicity screening. Zidek N, Kramer PJ, Hewitt PG (2005). Toxicology Letters, 158 (suppl. 1), S35
  • Gene expression in rat liver in vivo after exposure to the positive hepatotoxin lipopolysaccharide. Zidek N, Kramer PJ, Hewitt PG (2005). Toxicology Letters, 158 (suppl. 1), S36
  • Effects of cell culture on cell morphology and differential gene expression in primary rat hepatocytes. Hrach J, Hewitt PG (2005). Toxicology Letters, 158 (suppl. 1), S37
  • Effects of cell culture on primary hepatocytes – cell morphology and differential gene expression. Tuschl G, Hrach J, Hewitt PG, Mueller S (2005). Archives of Pharmacology, 371 (suppl.), R127
  • Gene expression in rat liver in vivo after exposure to the positive hepatotoxin lipopolysaccharide. Zidek N, Kramer PJ, Hewitt PG (2005). Archives of Pharmacology, 371 (suppl.), A496
  • Toxicogenomics applied to teratogenicity studies (2005). P G Hewitt, P-J Kramer and J Borlak. Toxicogenomics (J Borlak, ed) Wiley-VCH Verlag.
  • Phase 1 and 2 enzyme characterisation of two sources of HepG2 cell lines. Nicola J. Hewitt and Philip Hewitt (2004). Xenobiotica. 34(3):243-56
  • Systemic Toxicity. Philip Hewitt and Howard Maibach (2003) in: Condensed Handbook of Occupational Dermatology, Kanerva L, Elsner P, Wahlberg JE and Maibach HI (eds). Springer-Verlag, Heidelberg, pp. 25-33.
  • A toxicogenomic approach to predict teratogenicity of new drug candidates. Borlak J, Bosio A, Kramer P-J, Hewitt PG (2002). Toxicology Letters 135 (suppl. 1), S83
  • Gene expression profiling in cultures of HepG2 and primary human hepatocytes. Hewitt PG, Kramer PJ, Bosio A, Borlak J (2002). Toxicology Letters 135 (suppl. 1), S120
  • Polymers effect on estradiol partition coefficient between powdered human stratum corneum and water (2002). Wester RC, Hui X, Hewitt PG, Hostynek J, Krauser S, Chan T, Maibach HI.J Pharm Sci.  91(12): 2642-5.
  • Use of a reporter gene assay with known genotoxic compounds. Hewitt, PG, Kramer P-J, Schneider J (2000). Toxicology Letters 116 (suppl 1), 36
  • Dermatotoxicology. Philip Hewitt and Howard Maibach (2000) in: Cosmeceuticals: Drugs vs. Cosmetics, P. Elsner and H.I. Maibach (eds).Marcel Dekker Inc., New York, pp. 203-221.
  • Metabolism of fluroxypyr, fluroxypyr methyl ester and the herbicide fluroxypyr methylheptyl ester. I: During percutaneous absorption through fresh rat and human skin in vitro. Hewitt PG, Perkins J, Hotchkiss SAM (2000). Drug Metabolism and Disposition, 28 (7), 748-754.
  • 97. Metabolism of fluroxypyr, fluroxypyr methyl ester and the herbicide fluroxypyr methylheptyl ester. II: In rat skin homogenates. Enzyme kinetics and enzyme inhibition. Hewitt PG, Perkins J, Hotchkiss SAM (2000). Drug Metabolism and Disposition, 28 (7), 755-759.
  • 98. Systemic Toxicity. Philip Hewitt and Howard Maibach (2000) in: Handbook of Occupational Dermatology, Kanerva L, Elsner P, Wahlberg JE and Maibach HI (eds). Springer-Verlag, Heidelberg, pp. 43-55
  • 99. Dermatotoxicology. Philip Hewitt and Howard Maibach (2000) in: Handbook of Occupational Dermatology, Kanerva L, Elsner P, Wahlberg JE and Maibach HI (eds). Springer-Verlag, Heidelberg, pp. 32-421999
  • 100. In vitro cutaneous disposition of a topical diclofenac lotion in human skin: Effect of a multi-dose regimen. Philip G Hewitt, Nicholas Poblete, Ronald C Wester, Howard Maibach and J Zev Shainhouse (1999) in Percutaneous Absorption – Drugs – Cosmetics – Mechanism – Methodology, 3rd Edition, Bronaugh R and Maibach HI (eds). Marcel Dekker, New York, Chapter 54, pp. 915-928
  • In vivo bioavailability and metabolism of topical diclofenac lotion in human volunteers. Hui X, Hewitt PG, Poblete N, Maibach HI, Shainhouse JZ and Wester RC (1998). Pharmaceutical Research, 15 (10), 1589-1595.
  • In vitro cutaneous disposition of a topical diclofenac lotion in human skin: Effect of a multi-dose regimen. Philip G Hewitt, Nicholas Poblete, Ronald C Wester, Howard Maibach and J Zev Shainhouse (1998). Pharmaceutical Research, 15 (7), 988-992.
  • Metabolism of fluroxypyr methyl ester and fluroxypyr methylheptyl ester by rat skin homogenates in vitro. P. Hewitt, S.A. Hotchkiss and J. Perkins (1996). Human and Experimental Toxicology, 15 (9), 663.
  • Decontamination procedures after topical exposure to 4,4’-methylene-bis-2-chloroaniline and 4,4’-methylenedianiline to rat and human skin in vitro. P.Hewitt, S.A.M. Hotchkiss and J. Caldwell (1995). Fundamental and Applied Toxicology, 26, 91-98.
  • Transdermal metabolism of fluroxypyr methylheptyl ester during percutaneous absorption in vitro. P. Hewitt, S.A. Hotchkiss and J. Perkins (1995). In: Prediction of Percutaneous Penetration. Methods, Measurement and Modelling (Volume 4b), K.R. Brain, V.J. James and K.A. Walters (eds), STS publishing, Cardiff, pp. 233-2401994
  • In vitro:in vivo correlations in human skin absorption of pharmaceutical agents. P. Hewitt, K. Brockelsby and S.A.M. Hotchkiss (1994). British Journal of Clinical Pharmacology, 38 (2), 163P.
  • Percutaneous absorption of agrochemicals through human skin in vitro. P. Hewitt, S.A. Hotchkiss and J. Perkins (1994). Human and Experimental Toxicology, 13 (9), 638.1993
  • Cutaneous reservoir formation and localization after topical application of 4,4’-methylene-bis-2-chloroaniline and 4,4’-methylenedianiline to rat and human skin in vitro. P.G. Hewitt, S.A.M. Hotchkiss and J. Caldwell (1993). In: Prediction of Percutaneous Penetration. Methods, Measurement and Modelling (Volume 3b), K.R. Brain, V.J. James and K.A. Walters (eds), STS publishing, Cardiff, pp. 638-645.
  • Comparison of the percutaneous absorption of two formulations of fenazaquin through rat and human skin in vitro. P.Hewitt, S.A.M. Hotchkiss, W.L Chen, J.M. Perkins and R.R. Rowe (1993). In: Prediction of Percutaneous Penetration. Methods, Measurement and Modelling (Volume 3a) abstract, K.R. Brain, V.J. James and K.A. Walters (eds), STS publishing, Cardiff.
  • Percutaneous absorption of 4,4’-methylene-bis-2-chloroaniline and 4,4’-methylenedianiline through rat and human skin in vitro. S.A.M. Hotchkiss, P.Hewitt and J. Caldwell (1993). Toxicology in vitro, 7, 141-148.
  • Comparison of the percutaneous absorption of two formulations of fenazaquin through rat and human skin in vitro. S.A.M. Hotchkiss, P.Hewitt, W.L Chen, J.M. Perkins and R.R. Rowe (1993). In: Prediction of Percutaneous Penetration. Methods, Measurement and Modelling (Volume 3b) pp658-665, K. Brain, V. James and K. Walters (eds), STS publishing, Cardiff.
  • Comparison of the percutaneous absorption of MbOCA and MDA through rat and human skin in vitro. P.G. Hewitt, S.A. Hotchkiss and J. Caldwell (1992). Human and Experimental Toxicology, 11, 585.
  • Percutaneous absorption of nicotinic acid, phenol, benzoic acid and triclopyr butoxyethyl ester through rat and human skin in vitro: Further validation of an in vitro  model by comparison with in vivo data. S.A.M. Hotchkiss, P.Hewitt, J. Caldwell, W.L Chen and R.R. Rowe (1992). Food and Chemical Toxicology, 30, 891-899.
  • Percutaneous absorption of topically applied chemicals through human skin in vitro. S.A.M. Hotchkiss, A. Garnett, P. Hewitt, A. Mint and J. Caldwell (1992). British Journal of Clinical Pharmacology, 34, 148P.
  • Absorption of nicotinic acid, phenol and benzoic acid through rat and human skin in vitro. S.A.M. Hotchkiss, P.Hewitt, J. Caldwell, W.L. Chen and R.R. Rowe (1991). In: Prediction of Percutaneous Penetration. Methods, Measurement and Modelling (Volume 2) pp472-482, R.C. Scott, R.H. Guy, J. Hadgraft and H.E. Boddé (eds), IBC Technical Services.
  • Metabolism and disposition of topically applied chemicals in the skin. J. Caldwell, S.A. Hotchkiss, A. Garnett, P. Hewitt and P. Nasseri-Sina (1991). Acta Pharmaceutica Nordica, 3, 115.

Oral presentations:

  • Manchester; Biomarkers, 25-26th February
  • Kirkstall, Barcelona, 30 May – June 1st
  • Geneva lecture: 15th September
  • New Frontiers in 3D Conference. Baltimore, October 13th 2016. Physiological and Toxicological evaluation of advanced 3D liver models for toxicological profiling in the pharmaceutical industry. November, Lisbon
  • Potential translational safety biomarkers for the small intestine: miRNA vs CitrullinePresented at the annual EUROTOX meeting, 13th-16th September. Barcelona
  • The MIP-DILI initiative: physiological, pharmacological and toxicological evaluation of current and novel test systems for understanding hepatotoxicityPresented at the Predictive Toxicology Summit, 16th-18th february 2015, London
  • The MIP-DILI initiative. To be presented at the Tissue Engineering for Drug Development and Substance Testing (TEDD) “Advanced in vitro liver models for toxicological profiling”. June 24th 2014
  • Identifying biomarkers of kidney and liver toxicity by integrating toxicogenomics datasets with biological networks. Presented at the Biomarkers and Diagnostics World Congress, Philadelphia, May 6-8, 2013
  • SPS
  • Use of multiplex technologies for measuring biomarkers in early non-clinical safety assessment. Presented as part of the EMD Millipore Tox Webinar Series, May 3, 2013Renal Biomarkers. To be presented at the annual Safety Pharmacology Society meeting, Rotterdam, 18-19 September, 2013
  • State-of-the-Art Detection of Nephrotoxicity by Urinary Protein Biomarkers. Presented at the 6th Annual Biomarkers Congress, Manchester, 23-24 February 2012.
  • Validation of in vivo nephrotoxicity biomarkers and evaluation of an in-vitro nephrotoxicity screening system. Presented at the ADMET meeting, Brussels, 26th-27th January 2012
  • Biomarker World Congress, May 2011
  • State-of-the-Art detection of nephrotoxicity by urinary protein biomarkers. Presented at the 6th Annual Biomarker Congress (Oxford Global). 23rd-24th February, 2011
  • Profiling the toxicity of new drugs: A non-animal-based approach integrating toxico-dynamics and biokinetics. Presented at the ADMET meeting, Brussels, 27th-28th January 2011
  • Screening tools for toxicity and drug discovery. Presented at Cell Based Assay, London, 20-21 September, 2010. 
  • Technologies for identifying and analysing novel toxicity biomarkers, presented at the SMi Biomarker Summit, January 2010. 
  • INTEGRATION OF GENOMICS, PROTEOMICS AND METABOLOMICS TECHNOLOGIES IN DRUG SAFETY ASSESSMENT: The need for collaboration and external funding, presented at IUTOX, Barcelona, July 2010
  • Organised and Chaired Symposium at the 2009 Eurotox meeting in Dresden
  • Predictive Safety Biomarkers in Non-Clinical Development. Presented at The Biomarker World Congress, Philadelphia, March 2009
  • New assays/methods in molecular toxicology. Presented at the 4th Mannheimer Biotech-Workshop, March 2009
  • Predictive Safety Biomarkers in Non-Clinical Development. Presented at The 4th Annual Biomarker Congress, Manchester, February 2009
  • Improve Detection of Hepatotoxicity with Predictive Toxicogenomics Studies. Presented at Reducing Toxicity in drug compounds, London, January 2009
  • Presented at the 11th MipTec conference, Basel, October 2008
  • Predictive Toxicology – an Integrated Project within the “Innovative Medicinesfor Europe Initiative“. Presented at the Molecular Medicine TriConference, San Francisco, March 2008
  • Recent and future applications of DNA microarray technologies in toxicology. Presented at the Annual BTS congress, Guildford, April 2008
  • Predictive Toxicology in Europe - An Integrated Project within the 'Innovative Medicines for Europe' Initiative. Presented at the Discovery Summit, Monte-Carlo, March-April 2008
  • Predictive Toxicology – an Integrated Project within the “Innovative Medicinesfor Europe Initiative“. Presented at ADMET, Brussels, January 2008
  • Recent and future applications of DNA microarray technologies in toxicology. Presented at “Toxicogenomics in Drug Safety Assessment” London, December, 2007
  • In vivo : In vitro hepatotoxicity. A comparative toxicogenomics study with lipopolysaccharide. Presented at “Microarrays in Clinical Development – Maturation of an Exploratory Tool”. Berlin, September 2007
  • Gene expression profiling in toxicology studies. Presented at “Developments in Gene Expression Profiling”, London, May 2007
  • Applied Toxicogenomics: Evaluation of LPS-induced hepatotoxicity. Presented at the Molecular Medicine TriConference, San Francisco, March 2007
  • Early characterization of hepatotoxicants by focused Illumina microarrays. Presented at the World Pharmaceutical Congress, Philadelphia, May 2006
  • Establishment of Illumina Gene Expression Arrays for Hepatotoxicity Screening. Presented at the SOT, San Diego March 2006
  • Establishment of Illumina Gene Expression Arrays for Hepatotoxicity Screening. Presented at Drug Discovery Technology, Europe, London March 2006.
  • Examining the aim of alternative test systems. Presented at Applications for Risk Assessment in Pharmaceutical Toxicology, London November 2005
  • Early Detection of Liver Toxicity using Toxicogenomics. Presented at Predictive Toxicology in Early Drug Development, Amsterdam September 2004
  • Fine tuning the numerous data from toxicogenomics to produce an early assessment of potentially toxic compounds. Presented at the TOX ’03: Toxicology for the Pharmaceutical Industry, London, 9th December 2003.
  • Use of a Reporter Gene Assay for Toxicity Screening. Presented at the 6th Annual meeting of the Society of Biomolecular Screening, Vancouver, 8th September 2000.
  • Metabolism of fluroxypry methyl ester and fluroxypyr methylheptyl ester by rat skin homogenates in vitro. Presented at the British Toxicology Society meeting, York, 2nd April 1996
  • Transdermal metabolism of fluroxypyr, fluroxypyr methyl ester and fluroxypyrmethylheptyl ester during percutaneous absorption through human skin invitro. Presented at the Drug Metabolism Group meeting, St. Mary’s Hospital, 15th December, 1994

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