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Elizabeth (Liesbeth) de Lange

Professor Predictive Pharmacology

Name
Prof.dr. E.C.M. de Lange
Telephone
+31 71 527 6330
E-mail
ecmdelange@lacdr.leidenuniv.nl
ORCID iD
0000-0001-8303-1117

Prof. Elizabeth de Lange has been trained as a chemist, with a specialization in Biophysical Chemistry (Groningen University, The Netherlands). She obtained her PhD in Pharmacology (Leiden Academic Center for Drug Research (LACDR), Leiden University, The Netherlands). She currently is the Principal Investigator on Predictive Pharmacology in the Division of Systems Pharmacology & Pharmacy at the LACDR. Her aim is to adequately predict human drug effects using predictive pharmacological (translational) approaches.

More information about Elizabeth (Liesbeth) de Lange

Curriculum Vitae

Prof. Elizabeth de Lange (PhD, PharmDhc) is staff member at the Division of Systems Pharmacology & Pharmacy of the Leiden Academic Center for Drug Research (LACDR). She has been trained as a Biophysical Chemist and had her PhD in Pharmacology on “The use of microdialysis to study drug transport across the blood-brain barrier in health and disease”. 

Liesbeth’s ultimate aim is to predict human drug effects and early neurodegenerative disease stage by translational model development on the basis of preclinical and clinical data. To that end she underscores that the rate and extent of the body (biological systems) processes are condition dependent. Therefore, the mutual coherence and time dependencies of biological systems processes should be unraveled by strategic preclinical and clinical experimentation to obtain multilevel and longitudinal data combined with mathematical modelling (Mastermind Research Approach).

As the pharmacokinetics (PK) and pharmacodynamics (PD) of a drug are dependent on the interaction of the drug with the biological system, it depends on drug properties and rate and extent of biological systems processes. It is actually the understanding of the differences in the rate and extent of those processes between biological systems that forms the basis for interspecies and condition translation and prediction. Her research focusses on measurement of the PK of the drug in plasma; drug transport into and out of the target tissue; drug distribution within the target tissue; drug equilibration to the target site; and the ability of the drug to interact with the target, and (biomarkers of) the drug’s PD. These are interdependent. Particular emphasis lies on investigations on drug distribution to target tissues protected by special barriers, like the brain. A recent success has been the development of a physiologically-based multi-CNS compartment model that adequately predicts the PK of drugs in the different compartments of the mouse, rat and human CNS, only using the physico-chemical and biological properties of the drug.

As neurodegenerative diseases develop over time. For Alzheimer’s disease there is a lack of understanding on what makes the systems processes change in the onset of the disease, and how processes interact in disease progression. Especially the information on what causes the onset and early disease progression is important for developing intervening drugs before irreversible changes will dominate, to halt or even reverse the disease progression. Also here, the Mastermind Research Approach is applied, by measuring different endogenous compounds at different locations in preclinical species (including blood, Brain sites, CSF etc), at different stages in life. This will be translated to the human situation, and lay the foundation for a blood derived biomarker fingerprint, which is more patient friendly manner of a diagnose compared to a lumbar puncture for measuring in the cerebrospinal fluid (CSF), or (expensive) imaging modalities. Especially, a blood derived biomarker fingerprint of early stage AD would be of added value.

Liesbeth currently supervises the following PhD students and Postdocs:

  • Mohammed Saleh- PhD student
  • Berfin Gulave - PhD student
  • Divakar Budda - PhD student
  • Chunyuan Yin - PhD student
  • Mengxu Zhang - PhD student
  • Ming Sun - PhD student

Research Technician:

  • Dirk-Jan van den Berg

An overview of research projects at the Predictive Pharmacology group.

  • Prediction of human (CNS) target site concentrations in health and disease
  • Predicting early Alzheimer’s disease stage in human
  • Drug-target binding kinetics in vivo
  • Spatial (3D) CNS drug distribution model
  • Prediction of human gut (colon cancer) target site concentrations and PKPD relationships
  • Pharmacometabolomics; prediction of system-wide multi-biomarker drug response.

Research Interests and Experience

  • blood-brain barrier and blood-CSF-barrier transport
  • intracerebral distribution
  • role of transporters in (CNS) drug pharmacokinetics
  • application of population mechanism-based PK and PKPD modeling
  • development of physiologically based (PB) PKPD models
  • drug target binding kinetics models
  • translational approaches
  • prediction of drug effects
  • in vitro-in vivo correlations
  • theoretical studies, simulations, modeling
  • neurodegeneration – Alzheimer’s disease, Parkinson’s disease
  • biomarkers (drug effects, disease)
  • disease progression
  • prediction of disease stage
  • early disease biomarker fingerprints
  • application and improvement of quantitative technologies

Key Publications:

 

Professor Predictive Pharmacology

  • Science
  • Leiden Academic Centre for Drug Research
  • LACDR/Pharmacology

Work address

LMUY
Einsteinweg 55
2333 CC Leiden
Room number 00.20

Contact

Publications

  • In Focus - ecmdelange Geven van cursuseen (1 maal per jaar BBB cursus), geven van advies (kleine omvang, incidenteel)
  • InFocus-ecmdelange Geven van cursussen (BBB curus 1 jaarlijks), geven van advies (kleine omvang, incidenteel)
  • Infocus www.infocus-ecmdelange.nl Directeur / eigenaar
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