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Pharmacology: Olaf van Tellingen

Van Tellingen Liggend

Olaf van Tellingen, Ph.D.Group leader

About Olaf van Tellingen

Olaf van Tellingen

Glioblastoma (GBM) is a uniformly fatal disease. The location and invasive nature of GBM renders complete surgical resection impossible. Although radiotherapy is important for disease management, side effects prohibit the delivery of curative doses. Despite the successful introduction of novel targeted therapeutics in some other solid cancer types, clinical trials in GBM have all failed. The mission of our preclinical research group is to develop and validate more effective pharmacotherapies for this disease. One of the spearheads of our research is aimed at highlighting the important role of the blood-brain barrier (BBB) in treatment failures. Although disruption of the BBB is common, this grossly affects areas of the tumor that can be surgically resected. However, the non-resectable tumor cells that have colonized the surrounding normal brain tissue are protected by the BBB and are the source of the inevitable recurrence. Just a few mainly small hydrophobic drugs display some efficacy against GBM. In particular, drug transporting proteins like ABCB1 (P-gp) and ABCG2 (BCRP) hinder the entry of most of the other effective anticancer agents, including many targeted agents. Thus, in order to develop more successful pharmacotherapy, our research aims to identify potentially useful agents that are no or weak substrates of these drug transporters. Alternatively, we are trying to improve drug penetration into brain tumors by using drug efflux pump inhibitors or carrier systems. 

Other hurdles to effective pharmacotherapies for GBM are the combined activation of multiple oncogenic pathways and intra-tumor heterogeneity. With multiple aberrant signaling pathways driving GBM, single target-single agent pharmacotherapies are likely to fail, even when using drugs that can penetrate the BBB. Consequently, we are exploring combinations of targeted agent that should cause concomitant inhibition of the common glioma associated oncogenic signaling pathways. Moreover, as radiotherapy is the cornerstone of the standard therapy, we are also actively investigating the options of radiosensitization by small molecule drugs. For this we closely collaborate with the research group of Gerben Borst. 

GBM is a highly complex disease that cannot be modelled with high-fidelity using in vitro models only. Consequently, we rely heavily on in vivo models for our research. We have developed and acquired a range of experimental mouse models of GBM that mimic many aspects of GBM in patients very closely. These include genetically engineered mouse models and human and murine transplantable glioma models. With our top-class animal facility housing 7T MRI, image-guided radiotherapy system and molecular and optical imaging modalities, we can make optimal use our state-of the-art models for interrogating the effects of experimental interventions. The impact of the drug transporters in the BBB is being studied by using transporter knockout mouse models. In collaborations with the research group of Jacco van Rheenen we are also implementing intravital imaging as a tool to visualize the response of intracranial tumors to therapies. With the help of these models, we try to uncover potentially exploitable vulnerabilities of gliomas in order to improve the prospects of patients that suffer from this devastating disease.

Student positions Van Tellingen lab: If you are interested in performing a research internship (>6 months) in our lab, please send a motivation letter and CV to o.v.tellingen@nki.nl. Candidates with backgrounds in chemistry, biology, laboratory animal science and related fields are welcome to apply.

Co-workers

Ceren Citirikkaya

Ceren Çitirikkaya

Technician

Experience

I started my internship as a graduate student in the lab of dr. Olaf van Tellingen in 2016. My project was mainly focused on obtaining therapeutically active plasma levels in mice. I received my Bachelor of Science degree and animal experimental license from the University of Applied Sciences Leiden in 2017.

After my graduation I joined the Van Tellingen lab as a research technician, working on various in vitro and in vivo projects that aim to develop a better treatment for glioblastoma

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Çolakoğlu, Hilâl

Hilal Çolakoğlu

Technician

Experience

I joined the Van Tellingen lab in November 2017 as a bachelor student from the Biology and Medical Laboratory Research program at the University of Rotterdam of Applied Sciences. My main focus was studying the efficacy of motor protein inhibitors against glioblastoma. After obtaining my Bachelor of Science degree in July 2018, I have continued working in the Van Tellingen lab as a technician, mainly focusing on developing new treatment strategies for glioblastoma.

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De Gooijer, Mark

Mark de Gooijer

Postdoc

Experience

As a PhD student in the lab of dr. Olaf van Tellingen, my research mainly focuses on the treatment of brain tumors and overcoming the challenge that the blood-brain barrier poses to the development of effective therapies.

Prior to joining the Division of Pharmacology at the NKI, I received training as a student in the labs of prof. Thomas Wurdinger at the Cancer Center Amsterdam (CCA) and dr. Bakhos Tannous at Massachusetts General Hospital, Boston, whilst obtaining my Master of Science degree in Oncology from VU university in Amsterdam.

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Research updates View All Updates

  • Pint of Science Festival

    The Pint of Science festival aims to deliver interesting, fun, relevant talks on the latest science research in an accessible format to the public - all in the pub! During the upcoming edition on May 20th, Paul Slangen, Mark de Gooijer and Inge Verbrugge will be hosting an evening themed 'The Brain: can we beat this obstacle course?'.

    The event is freely admissible, but registration is required and can be done by following the link below. We hope to see you all there!

     

    The Brain: can we beat this obstacle course?
  • Thesis Mark de Gooijer

    On Wednesday January 23rd, 2019, Mark de Gooijer defended his thesis in Pharmaceutical Sciences at the University of Utrecht and was honoured with a cum laude distinction. He was also awarded a silver UIPS medal.

    Mounting an attack on the glioblastoma triad: proliferation, invasion and resistance.

    Malignant brain tumors respond very poorly to treatment because of uncontrolled cell proliferation, strong invasiveness and resistance to therapy. PhD researcher Mark de Gooijer has shown that, although new treatments can efficiently attack each of these problems separately, combining them will be necessary to provide better prognoses for patients with brain tumors.

    https://www.uu.nl/en/background/mounting-an-attack-on-glioblastoma

    https://stophersentumoren.nl/Archief2019/mark-de-gooijer-verdedigde-met-succes-zijn-hersentumorproefschrift

Key publications View All Publications

  • Identification of a druggable pathway controlling glioblastoma invasiveness.

    Cell Rep. 2017;20(1):48-60

    Pencheva N, De Gooijer MC, Vis DJ, Wessels LFA, Wurdinger T, Van Tellingen O, Bernards R.

    Link to PubMed
  • Overcoming the blood-brain tumor barrier for effective glioblastoma treatment

    Drug Resist Updat. 2015;19:1-12

    Van Tellingen O, Arik-Yetkin B, De Gooijer MC, Wesseling P, Wurdinger T, De Vries EH.

    Link to PubMed
 
 

Recent publications View All Publications

  • MELK Inhibition in Diffuse Intrinsic Pontine Glioma

    Clin Cancer Res. 2018 Nov 15;24(22):5645-5657. doi: 10.1158/1078-0432.CCR-18-0924. Epub 2018 Jul 30

    Meel MH, De Gooijer MC, Guillén Navarro M, Waranecki P, Breur M, Buil LCM, Wedekind LE, Twisk JWR, Koster J, Hashizume R, Raabe EH, Montero Carcaboso A, Bugiani M, Van Tellingen O, Van Vuurden DG, Kaspers GJL, Hulleman E.

    Link to Pubmed
  • ABCB1 Attenuates the Brain Penetration of the PARP Inhibitor AZD2461

    Mol Pharm. 2018 Nov 5;15(11):5236-5243

    De Gooijer MC, Buil LCM, Çitirikkaya CH, Hermans J, Beijnen JH, Van Tellingen O

    Link to PubMed
 

Contact

  • Office manager

    Thea Eggenhuizen

  • E-mail

    t.eggenhuizen_at_nki.nl

  • Telephone Number

    020-5122035

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