This website uses cookies

This websites contains videos from YouTube. This company uses cookies (third party cookies). If you do not want them to use these cookies, you can indicate so here. However, this does mean that you will not be able to watch videos on this website. We also make use of our own cookies in order to improve our website. We don't share our data with other parties. Which cookies are involved?

This website uses cookies to enable video and to improve the user experience. If you do not want to accept these cookies, indicate so here. Which cookies are involved?

Ga direct naar de inhoud, het hoofdmenu, het servicemenu of het zoekveld.

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

silhouette_geen_foto_thumb_vrouw.jpg

Chrysiida Baltira

Ph.D. student

Experience

As an undergraduate student I received my training at Karolinska Institute, Stockholm. After my graduation I pursued a master's degree in Neurosciences at VU University in Amsterdam, including an internship at the Netherlands Institute for Neuroscience. Having an interest in neuro-oncology I joined the group of dr. Olaf van Tellingen to perform my Master thesis work.

Following my graduation I continued working in the lab as a PhD student. My project aims to identify the molecular signaling cascades triggered by therapy-induced senescence in glioblastoma. My ultimate goal is to provide glioblastoma patients with improved treatment options.

Close this window
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

Close this window
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.

Close this window
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.

Close this window

Research updates View All Updates

  • Vacancy PhD Student

    Preclinical Pharmacokinetics - Pharmacodynamics of small molecule drugs for treatment of cancer.

    Your function within the department

    One of the research aims of the research group of Olaf van Tellingen at the Division of Pharmacology is to improve the predictive value of preclinical murine models of cancer. Although the work in his team is centered around brain tumors, the scope of this project will also be on other tumor types. Mouse models of cancer are central in the development of anticancer therapy. Unfortunately, promising results observed in preclinical models often fail to translate to clinical benefit in patients. Although there likely are several factors that contribute to this lack of predictivity, one often neglected aspect is the pharmacological translation from experimental species to patients. In this project, you will investigate the pharmacokinetic - pharmacodynamic (PK-PD) relationship of anticancer drugs and their respective targets in preclinical models. You will focus on the differences in drug exposure between rodents and humans and drug distribution between ectopic and orthotopic tumor models. The ultimate aim of the project is to demonstrate how taking the pharmacological translation into consideration can improve the predictive value of preclinical cancer models.

    Your profile

    We are seeking an ambitious, highly motivated PhD student with a strong commitment to science and a keen interest to work at the intersection of Pharmacology and Medical biology. You are attracted to interact in a strong team, but capable to work independently. This work will involve analytical (LC-MS/MS) and biological assays, in vitro (cell culture) and in vivo (mouse/rat) models. An MSc in Pharmacology or Oncology and experience with any of these techniques is advantageous. The possession of or commitment to acquire an animal license (Art. 9) is mandatory.

    You will join a dynamic international research division and collaborate with scientists and clinicians within and outside the NKI-AVL with expertise in different disciplines. Graduate students at the NKI participate in the education program of the Oncology Graduate School (OOA) Amsterdam. Supervision and promotion of career will be carried out by experts in their respective fields.

    Your career opportunities and terms of employment

    Your temporary employment is for a period of 4 years with a possible extension of another year. The gross salary per month will be from € 2,798 to € 3,446, according to the standard PhD scales. The terms of employment will be in accordance with the CAO Ziekenhuizen (Collective Labour Agreement for Hospitals) and can be consulted at http://www.nvz-ziekenhuizen.nl/cao-kenniscentrum/cao/download

    Amsterdam is a very lively city with many cultural amenities. The institute is located within a 20 minute tram or bicycle ride from the city center and within 20 minutes from Schiphol airport by car, bus or bicycle.

    Interested?

    For further information about the position, please contact. dr. Olaf van Tellingen, Division of Pharmacology (tel. +31 20 512 2792, e-mail o.v.tellingen@nki.nl). To apply for the position, please follow the link below.

    Apply for the position
  • 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

    https://medidact.com/oncologie/het-opzetten-van-een-gelijktijdige-aanval-op-de-glioblastoomtriade/

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

  • MEK/MELK inhibition and blood-brain barrier deficiencies in atypical teratoid/rhabdoid tumors.

    Neuro Oncol. 2020;22(1):58-69

    Meel MH, Guillen-Navarro M, de Gooijer MC, Metselaar DS, Waranecki P, Breur M, Lagerweij T, Wedekind LE, Koster J, van de Wetering MD, Schouten N, Aronica E, van Tellingen O, Bugiani M, Vandertop WP, Phoenix T, Kaspers GJL, Hulleman E.

    Link to PubMed
  • 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
 

Contact

  • Office manager

    Lara Spee

  • Telephone Number

    +31 20 512 2035

Share this page