Division of Molecular and Computational Toxicology

Division of Molecular and Computational Toxicology is specialized in developing strategies for the understanding and prediction of kinetics and safety of chemicals (including pharmaceuticals) and nanoparticles. The primary focus tissues are the liver and kidney. The research combines and integrates several tracks:

  1. Experimental approaches for phase I and phase II metabolism prediction including the influences of polymorphisms
  2. Computational methods for metabolism prediction 
  3. In vitro experimental approaches focusing on molecular mechanisms of chemical induced perturbations and associated stress. 

Activities also include defining and verifying adverse outcome pathways (AOPs) and development and deployment of software solutions to manage advanced in silico workflows. 

The laboratory is a specialized in:

  • analytical chemistry
  • cell culture
  • toxicity determination
  • omic analysis

The group is a partner in several EU level projects on drug and chemical safety including EUToxRisk, OpenRiskNet, in3 and the recently finished IMI projects StemBANCC and MIP-DILI.

Prof. Dr. Paul Jennings

Paul-JenningsPaul Jennings is the Chair of the Division of Molecular and Computational Toxicology, VU, Amsterdam. His background is in epithelial and renal biology, in vitro cell culture system development and mechanistic toxicology. Current research interests include:

  • Development of improved human renal and hepatic in vitro models
  • Mechanistic understanding using integrated omic approaches in carefully designed exposure scenarios (transcriptomics, proteomics, metabolomics and epigenetics)
  • The understanding of how cells deal with stress and the delineation of stress response pathways, including oxidative stress (Nrf2), DNA damage (p53), hypoxia (HIF-1alpha) and the unfolded protein response.
  • Chemical induced dedifferentiation and recovery after exposure
  • In vitro biokinetic studies
  • Integrating cheminformatics, kinetics and dynamics into computational systems toxicological models
  • Collaboration with specialists to build tiered integrated approaches for testing and assessment (IATA) / integrated testing systems (ITS) – (eg. BBB, liver, lung, brain, heart, skin) which are regulatory relevant (i.e. built with application to Adverse Outcome Pathways)
  • Understanding genetic diversity of dynamics and kinetics using iPSC.
  • Development of clinically-translational mechanistic biomarkers

Links: VU Research Portal, Pubmed, Google Scholar, Research Gate
Projects: in3 project, EUToxRisk, OpenRiskNet
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Assoc. Prof. Dr. Jan N.M. Commandeur

Jan CommandeurJan Commandeur studied Pharmacochemistry at the Vrije Universiteit Amsterdam. He graduated in 1985 with a specialization in Molecular Toxicology. He obtained his PhD in 1991 at the Vrije Universiteit on the subject: “Molecular Mechanisms of Chemically Induced Nephrotoxicity:  role of the mercapturic acid pathway in the bioactivation of halogenated hydrocarbons.” He was appointed as assistant and associate professor in 1991 and 2006, respectively, at the division of Molecular and Computational Toxicology at the Vrije Universiteit, Amsterdam.

His research interests are focused on the role of drug metabolism in the toxicity of drugs, and the consequences of genetic polymorphisms of drug metabolising enzymes as risk factors for toxic side effects of drugs, with special interest in drugs causing idiosyncratic liver toxicity and agranulocytosis. 

These studies include:

  • Characterization of wild-type and mutants of drug metabolising enzymes involved in formation and inactivation of reactive metabolites of drugs: e.g. human cytochromes P450, peroxidases, UGTs glutathione S-transferases and quinone reductases.
  • Characterization of the reactive drug metabolites and their cellular targets.
  • Simulation of the consequences of variability of bioactivating and inactivating enzymes using recombinant human enzymes and cell lines overexpressing drug metabolizing enzymes.  
  • Development and application of novel mutants of bacterial CYP102A1 (P450 BM3) which can be used as biocatalysts for large scale production of human drug metabolites and which can serve as model proteins for biochemical, biophysical and computational studies into the mechanism of action of P450s.  
  • Characterization of essential cytochrome P450s from Mycobacterium Tuberculosis as potential targets for new generations of antituberculosis drugs.

Links: VU Research Portal, PubMed

Ass. Prof. Dr. Chris Vos

Chris VosDr. ir. J.C. Vos studied Molecular Sciences at the Agricultural University of Wageningen. He received his PhD in 1993 at the University of Amsterdam for his work carried out at the European Molecular Biology Laboratory (EMBL) at Heidelberg, Germany, on vaccinia virus gene regulation. He spent two post-doctoral terms at the Dutch Cancer Institute in Amsterdam studying (i) DNA transposition in Caenorhabditis elegans, and (ii) the structure of the human Transporter Associated with Antigen Processing. In 2000, he moved to the section of Biochemistry and Molecular Biology (BMB) of the Vrije Universiteit focusing on the macromolecular interactions involved in the biogenesis of ribosomes in Saccharomyces cerevisiae. Since June 2006, he is member of the section of Molecular Toxicology, studying (i) stress-responses in yeast and human cells related to drug bioactivation by cytochrome P450 biotransformation, (ii) characterizing biotransformation enzymes and (iii) phenotyping primary human hepatocytes.

Link: VU Research Portal

Ass. Prof. Dr. Daan Geerke

Daan GeerkeDaan Geerke obtained his PhD degree in 2007 within the Laboratory for Physical Chemistry at the ETH Zürich, under supervision of Prof. Dr. Wilfred F. van Gunsteren. Afterwards he joined the research group of Dr. Julia E. Rice and Dr. William C. Swope at the IBM Almaden Research Center in San Jose, California, for a postdoctoral fellowship. In 2009 Daan Geerke has been appointed assistant-professor within MCT. Currently, he is as associate-professor supervising a senior scientist and three PhD students, and he lectures a variety of bachelor and master courses in the fields of computational chemistry, (bio-)molecular modeling, structural biology and (statistical) thermodynamics. 

His research focuses on in silico rationalization and prediction of drug metabolism and action upon binding to flexible enzymes such as human and bacterial Cytochrome P450s, proteases or methyl transferases, in direct collaboration with ‘wet-chemistry’ colleagues within MCT, VU medical centers and industry. In addition he has since many years worked on development of biomolecular force fields and on inclusion of quantum and electronic polarization effects in simulation. 

He has published more than 40 scientific publications within these research fields. In 2009, he has been awarded a NWO-Veni grant, in 2013 he has been awarded a NWO-Vidi grant, in 2015 a NWO / NLeSC eScience grant (together with prof. Gunnar Klau / CWI) and since 2016 several HPC grants from the VU High Performance Computing council. In addition, he has been coordinator of scientific activities at VU University in the context of the H2020 OpenRiskNet project and the IMI-JU eTOX project on in silico prediction of toxicities.

Link: VU Research Portal
Projects: NWO-Vidi, NLeSC-ASDI, OpenRiskNet

Dr. Anja Wilmes

Anja-WilmesAnja Wilmes graduated with a Diplom in “Biology” from the University of Heidelberg, Germany in 2004. She then completed her PhD thesis in “Cell and Molecular Biology” in 2008 at Victoria University of Wellington, New Zealand under thervision of Prof. John Miller. Her PhD thesis was entitled “Differences  in Mode of Action between Peloruside A and Paclitaxel, two Microtubule Stabilizing Agents”. She joined Pauls Jenning’s group at the Medical University of Innsbruck, Austria as a PostDoc in 2009 where she habilitated in “Physiology” with the thesis "Molecular investigations of chemical stress induction in the renal proximal tubule” in 2016. Her work focuses on the development of human renal cell culture models for toxicity screening with a major focus on iPS cell differentiation into proximal tubular cells and glomerulus cells. She is currently involved in the StemBANCC and the in3 project. Her works also focusses on studying functional roles of claudin expression and water transport in renal proximal tubular epithelial cells. In 2017, she moved with the Jennings group to the Vrije Universiteit Amsterdam in the Netherlands. 

Links: Pubmed, Google Scholar, Research Gate

Dr. Alice Limonciel

Alice-LimoncielAlice Limonciel studied the life sciences at the University of Nice - Sophia-Antipolis, France, before entering the engineer school Polytech’ Nice-Sophia in 2005. In Polytech’, she first studied pharmacology before specialising in toxicology. She graduated with an Engineer’s degree in "Toxicology and Health and Environment Security" in 2008. Dr. Limonciel completed her PhD entitled "Characterisation of the molecular stress responses of cultured human renal proximal tubule cells exposed to industrial and pharmaceutical nephrotoxins" in the Renal group of the Department of Physiology and Medical Physics of the Medical University of Innsbruck, Austria, in October 2013. She received several prizes for her work on mechanistic toxicology, including the Lush prize for Young Researcher in 2013 and the CEFIC-LRI award in 2015. Dr. Limonciel’s work is focused on the molecular responses of mammalian cells to xenobiotics and stress, with a particular focus on stress response pathways and the use of omic methodologies to unravel mechanisms of toxicity.

Links: Pubmed, Google Scholar, Research Gate

Giada Carta.MSc

Giada-CartaGiada Carta graduated with a bachelor in Cellular and Molecular Biology at the University of Rome “Tor Vergata” in 2012 with a neuroscience based experimental thesis performed at Medical University of Innsbruck. She continued her studies at the Leopold-Franzens-University in Innsbruck, and graduated with a Master in Cell Molecular and Developmental biology in 2015. In 2016 she started her PhD in the Molecular Cell Biology program under the supervision of Ass. Prof. Priv.-Doz. Dr. Paul Jennings in the renal group at the Division of Physiology of the Medical University Innsbruck.Her study focuses on the development of integrated testing strategies for in vitro assessment of chemical induced organ injury via mitochondria-mediated toxicity to predict human in vivo adverse outcome as part of the EU-ToxRisk21 project. In 2017 she moved with the Jennings lab to the division of Molecular and Computational Toxicology at the Vrije Universiteit, Amsterdam.

Link: VU Research Portal, Pubmed

Vidya Chandrasekaran.MTech

Vidya-ChandrasekaranVidya Chandrasekaran received the integrated Master’s degree in Industrial Biotechnology from the SASTRA University, India in 2015. For her Master’s thesis, Vidya worked in the Laboratory of Kidney Toxicology and Regeneration, Brigham and Women’s Hospital, Boston, towards understanding the pathophysiology of kidney disease. She also had a yearlong experience in developing a cell based bioassay for identifying predictive toxicity signatures at Laboratory of System Pharmacology, Harvard Medical School, Boston. To advance her scientific knowledge in the field of invitro toxicology, she joined in3 project through Prof. Dr. Paul Jennings’s lab at the Division of Molecular and Computational Toxicology, Vrije Universiteit, Amsterdam. Her work focuses mainly on differentiation of renal proximal tubule-like cells from iPSC and application to nephrotoxicity testing.

In3 website

Cormac Murphy.MSc

Cormac-MurphyCormac Murphy gained his undergraduate degree in Zoology from Trinity College Dublin in 2014 with a thesis project in the field of Developmental Biology. He graduate with an MSc in  Regenerative medicine from National university of Ireland Galway in 2015 where he worked on a project to model a rare form of familial retinitis pigmentosa using induced pluripotent stem(iPS) cells. He worked for fifteen months as a research scientist in Biotalentum, Hungary. In 2017 he stared his PhD as part of the Marie Skłodowska- Curie - International Training Network In3 project under the Supervision of Prof. Paul Jennings in the Molecular and Computation Toxicology division of the Vrije Universiteit, Amsterdam. His project focuses on the generation of a glomerular model from IPS cells and their application for nephrotoxicity testing. 

Links: VU Research Portal, In3 website

Sandra Ortega Ugalde. MSc

Sandra OrtegaSandra Ortega Ugalde, MSc. studied Pharmacy at the University of the Basque Country (Spain) and worked thereafter as a pharmacist in Ireland for two years. In 2013 she started the Master in Drug Discovery and Safety at the Vrije Universiteit (VU), Amsterdam, where she graduated with specialization in Molecular Toxicology. In July 2015, Sandra was awarded with one of the personal NWO AIMMS STAR (scientific top training in antimicrobial research) grants in the field of antimicrobials. With this grant Sandra started in September 2015 with a PhD research in the Molecular Toxicology and Molecular Microbiology research groups at the VU University. Her research aims at novel strategies to target Mycobacterium tuberculosis drug resistance by identifying and inhibiting constitutive and stress-induced mycobacterial cytochromes P450s (P450s) that are essential for the survival of the pathogen, avoiding off-target interaction with human P450s.

Links: VU Research Portal, Pubmed