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Olaf van Tellingen group

Van Tellingen Liggend

Olaf van Tellingen

Group leader

Personal details

Experience

Research interests include bioanalysis, LC-MS/MS, pharmacokinetics, mouse models of cancer and intervention studies. A major focus of my research is on the treatment of brain tumors, in particular glioblastoma, but also of metastatic brain cancer. For this research we closely collaborate with other investigators inside the Netherlands Cancer Institute (i.e. Gerben Borst, radiotherapy; Leila Akkari, brain tumor microenvironment; Jacco van Rheenen, intra-vital imaging; Rene Bernards, Targeted agents and senescence) and outside the institute, e.g. Prof Tom Wurdinger (VUMC), Dr Esther Hulleman (VUMC). Next to this work on brain tumors, my work also involves the support of intervention studies conducted by the Mouse Cancer Clinic to test novel therapies for other cancers. To this end, we conduct pharmacokinetic-pharmacodynamic studies in order to assess the systemic and tumor drug exposure in relation to the exposure in patients.

Genetic engineering and improvements in human tumor xenografts have allowed us to create mouse models of cancer that much better recapitulate the biology of the tumor as seen in cancer patients. The next challenge is to improve the predictive value of these mouse models for the treatment of cancer patients. By my work, I would like to emphasize the importance of considering the pharmacological aspects. Species differences in drug handling between mice and humans exist and may jeopardize the predictive value of preclinical studies, but using realistic systemic drug exposures as an integral part of adequate study design may help to bridge this gap.   

 Biographic sketch: Olaf van Tellingen graduated in medical chemistry (HBO-B) at the van den Broek Institute in Amsterdam in 1986. At that time he was appointed at the clinical chemistry lab of the Netherlands Cancer Institute / Antoni van Leeuwenhoek hospital where he started the implementation of HPLC for diagnostic purposes. In 1988 he joined the pharmacology working group that was initiated by Prof. Jos Beijnen, who was then recently appointed as hospital pharmacist. He graduated in 1993 at the University of Utrecht on his work on the development of bioanalytical assays and the implementation of these assays for preclinical pharmacological research. After his graduation in 1993 he remained working in the Netherlands Cancer Institute as a postdoc and associate research scientist and currently as group leader.

The bioanalytical work performed during preparation of his thesis was the basis for collaborations with Prof Piet Borst and Dr Alfred Schinkel who in 1993 had just developed the P-glycoprotein (P-gp) knockout mouse model. This and subsequently generated ABC-transporter knockout mouse models have greatly enhanced our insight in the role of ABC-transporters in xenobiotic handling of the body. The most striking results were the impact of ABC-transporters on the oral bioavailability of drugs and the protection of the brain. The finding that P-gp, and, later, also BCRP limit the brain penetration of many compounds, including many anticancer drugs, was the reason to start a research line to assess the impact of this limited brain penetration on the treatment of brain tumors. For this purpose he has spent 6 months (1996-1997) in the lab of Prof I.J. Fidler (MD Anderson Cancer Center, Houston) for training in orthotopic tumor models, in particular to learn the intracarotid injection of tumor cells as method to create brain metastases. Once back in Amsterdam, he introduced stereotactic intracranial tumor cell injections to create brain tumor models and later he generated genetically engineered mouse models of high-grade gliomas based on the Cre-loxP conditional mice developed in the lab of Prof Anton Berns. These models have now been used in several studies to demonstrate that ABC-transporter expression at the blood-brain tumor barrier indeed attenuate the efficacy of therapies against intracranial tumors.

Between 1993 and now he was co-promoter of nine PhD students and supervised numerous master students, undergraduate students and technician students.

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