My group aims to facilitate the drug development process by integrating existing data. The biomedical life sciences have progressed considerably in the last decade. This has resulted in an enormous amount of publications and related information, which opens up opportunities but also poses challenges. Integrating the available information with the help of artificial intelligence (AI) may yield new insights, reveal connections between physiological systems and predict drug effects which can all aid the drug discovery process. In the meantime, we need ways to adequately assess and weigh the quality of the available data.
In our group we make use of these opportunities and address the challenges. Our projects primarily center around the analysis, mapping and prediction of pharmacological processes. Projects range from machine learning and meta-analyses of preclinical studies, via characterization of ADME processes, and mapping of adverse outcome pathways to pharmacoepidemiological studies, biomarker identification and clinical studies.
We have a special interest in psychoneuroimmunopharmacology. With our projects we identify novel drug targets, generate maps for complex systems, build new hypotheses, and identify knowledge gaps for further research in this field. From a methodological point of view, our research may help define best practices for animal studies and inform human studies as well as in vitro models for disease.
We work closely together with the immunopharmacology and experimental pharmacology groups within our Pharmacology division, and collaborate with the division of pharmacoepidemiology and clinical pharmacology within UIPS.
Impact of data synthesis in pharmacology (2014-2024)
- Mechanism of action & disease pathways
- We identified components of anxiety that are affected by SSRIs (Heesbeen et al 2023, 2024)
- We mapped how TNFalpha may affect conditioned fear (adjusted AOP approach; Heesbeen et al, 2024, major revision)
- we provided an overview of the microbiome in animal models for Parkinson’s disease (Elford et al., SRMA ongoing)
- Worked examples / sharing methods & method development:
- IB deRisk tool: concentration- effect analysis of cannabidiol (Kwee et al, 2022)
- Risk of bias assessment tool in vitro studies (under review; Hameete et al)
- Bayesian meta- analysis for small sample studies (animal studies; Kwee et al, 2023; Heesbeen et al., 2023)
- Adjusted AOP approach in neuro-immune research (major revision)
- Target evaluation
- Evaluation of endocannabinoid enhancing drugs ~anxiety disorder (Kwee et al., 2023)
- Minor endocannabinoids: an inventory of their potential for treatment of psychiatric disorders (under review; diGamma et al)
- Research methods: 3Rs, Validity and Translational value of animal models
- BBB permeability and conventional photon radiotherapy (radiation exposure (clinical gain) and model selection (preclinical gain) (t Hart et al, 2022 )
- Renal drug clearance; methods and validity: what species to use (Jansen et al, 2020)
- Unconditioned anxiety (GPDV); 3Rs
- Conditioned anxiety (Fear potentiated startle); translational value, methodology
Recent grants:
PhD project (2019): Role of the immune system in the development of anxiety disorders
NWO-TTW grant (2018): Maternal immune activation during pregnancy –a dietary intervention to restore immune fitness in the offspring (2018). Post-doctoral position and 2 graduate students, in collaboration with dr A Hogenkamp (UU) and dr T Plosch (UMCG).
- Bart Hameete
- Naomi Hofsink
ZonMW Meer Kennis met Minder Proefdieren. Programma Synthesis of evidence in de praktijk.
-Pharmacology of the fear-potentiated startle (2020).
-Interspecies Differences in Renal Clearance Based on Physicochemical Drug Properties (2018) ism prof dr R Masereeuw, K Janssen & C Pou Casellas;
-Prenatal maternal infection: a systematic review on immune parameters in the poly(lC) model (2017).
NWO Food, Cognition & Behaviour program (2014). Prenatal maternal infection: how diet influences behaviour in the offspring. Post-doctoral position, in collaboration with dr A Hartog (Nutricia Research), dr A Hogenkamp (UU) and dr L de Witte (UMCU).
ZonMW Program Translational Research (2014) Co-applicant, in collaboration with dr JMP Baas (Fac Social Sciences),dr DC Cath (Altrecht), prof AJLM van Balkom (Ingeest VuMC) and dr N Batelaan (Ingeest VuMC). Augmentation treatment with cannabidiol in combination with exposure therapy in treatment refractory social anxiety and panic disorder patients.
Graduate students and finished graduate projects
Hameete B (2019-present) Prenatal maternal infection and immune function in the offspring. Promotores dr L Groenink, prof J Garssen, co-promotor dr A Hogenkamp, prof T Plosch (UMCG)
Hofsink N (2019-present) The consequences of maternal immune activation- Fetal programming by early life exposure. Promotores Prof dr T Plosch (UMCG), co-promotor dr L Groenink
Heesbeen EJ (2019- present) Role of the immune system in the development of anxiety disorders. Promotores dr L Groenink, prof J Garssen, co-promotor dr EY Bijlsma
Kwee C (2024) Cannabidiol in the treatment of anxiety. Promotores JMP Baas, D Cath, A van Balkom; co-promotores N Batelaan & L Groenink
Zhao Y (2019) Studying experimental factors to optimize the translational value of the rat fear-potentiated startle paradigm. Promotor: prof dr J Garssen; copromotores dr L Groenink, dr EY Bijlsma.
Milienne-Petiot MBM (2018) Manipulating the dopaminergic system to delineate mechanisms contributing to aspects of bipolar mania. Promotores: prof dr M Geyer (UCSD), prof dr J Garssen; copromotores: dr J Young (UCSD), dr L Groenink.
Douma TN (2013) CRF, stress and psychosis, Utrecht University. Promotor: prof dr B Olivier, copromotor: dr L Groenink.
Bijlsma EY (2010) CRF system out of control - implications for affective disorders. Promotor: prof dr B Olivier, copromotor: dr L Groenink.
Vinkers CH (2009) cum laude. Brain mechanisms underlying Stress-induced hyperthermia. Promotor: prof dr B Olivier, co-promotores: dr L Groenink, dr SM Korte.
Breuer ME (2009) Chronic animal models of depression. Utrecht University. Promotor: prof dr B Olivier, co-promotores: dr L Groenink, dr RS Oosting.
van Bogaert MJV (2006) Predisposed to anxiety. Utrecht University. Promotor: prof dr B. Olivier, co-promotores: dr L. Groenink, dr RS Oosting.
van den Bergh FS (2006) Targetting impulsivity. Utrecht University. Promotor: prof dr B. Olivier, co-promotores: dr RS Oosting, dr L. Groenink.
de Jongh R (2003) Fear versus anxiety- the role of corticotropin releasing factor. Promotor: prof dr B. Olivier, co-promotor: dr L. Groenink.
Pattij T (2002) 5-HT1A receptor knock-out mice and anxiety – behavioral and physiological studies. Promotor: prof dr B. Olivier, co-promotores: dr L. Groenink, dr J. van der Gugten.
Dirks A (2001) Corticotropin-releasing hormone, stress and anxiety- physiological, neuroendocrine and behavioral studies. Utrecht University. Promotor: prof dr B. Olivier, co-promotores: dr L. Groenink, dr J. van der Gugten.
Research Qualifications:
Senior research qualification (SKO, since 2007), Certified Pharmacologist (since 2012)