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Cell Biology: Prof. dr. Marcel Verheij

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Marcel Verheij M.D. Ph.D. professorGroup leader

About Marcel Verheij

Targeted Radiosensitization

The research activities of our group extend on the interface between lab and clinic. It focuses on the identification, preclinical testing, clinical evaluation and response prediction of targeted radiosensitization.The ultimate goal is to translate these strategies into clinical application.

In close collaboration with other research groups within the NKI, new agents are identified on the basis of their mechanism of action and subsequently tested for their ability to induce (apoptotic) cell death and to increase the cytotoxic effect of radiation in vitro and in vivo. These include synthetic alkylphospholipids (Perifosine), death receptor ligands (TRAIL, CD95L), small molecule inhibitors of Bcl-2 (Gossypol, ABT-737) and PARP inhibitors (APO866, Olaparib). Our recently acquired image-guided mouse irradiator (µIGRT) unit allows us to mimic clinical protocols and optimize the safe and effective radio-sensitizing capacity of novel compounds.

In a separate project we investigate the patented concept of improved anti-cancer drug delivery by short chain sphingolipid-enriched liposomes (GC-LipoDox®) in vitro and in vivo to overcome drug resistance. We identified a well-defined class of sphingolipid analogs that effectively catalyzes drug-membrane traversal preferential for tumor cell membranes. A liposomal co-formulation of the short-chain lipid N-octanoyl-glucosylceramide (GC) and doxorubicin generated a sustained anti-tumor response and significantly improved overall survival in a genetically engineered mouse breast tumor model. Recently, we unraveled the underlying molecular mechanism that promotes this trans-membrane movement of doxorubicin. Our well-defined lipid analogues adapt to the amphiphilic drug doxorubicin, when co-inserted into the cell membrane, and assemble a transient channel that rapidly facilitates the translocation of the drug onto the intracellular membrane leaflet.

Co-workers

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Elisabetta Argenzio

Postdoctoral fellow

Experience

I received my PhD at the European School of Molecular Medicine in Milan (Italy), particularly focusing on molecular oncology. Since 2009, I have been working as a postdoctoral fellow at the NKI.

The Moolenaar lab recently discovered that LPA-induced RhoA activation leads to a rapid and reversible recruitment of the Chloride Intracellular Channel 4 (CLIC4) protein to the plasma membrane. My goal is to elucidate the biological function of CLIC4 as a novel player in Rho signaling and intracellular trafficking. I am addressing this issue by using biochemical assays and imaging techniques.

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Conchita Vens Ph.D.

Senior scientist

Experience

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Shuraila Zerp, MSc

Research technician

Experience

Shuraila Zerp has been working as a (senior) research technician in the lab of Marcel Verheij since 1997. She has worked  in the radiation research field, on apoptosis, cell signaling, angiogenesis, cell membrane trafficking, DNA repair pathways, and radiosensitizers, in vitro as well as in vivo. Gradually, the research has evolved from basic science biochemistry in the nineties, to translational research with a focus on preclinical research of clinically applicable strategies, nowadays.
Experienced in: in vitro cell culturing, western blotting, apoptosis assays, FACS analysis, biochemical assays, molecular biology, proliferation assays, immunohistochemistry, clonogenic survival assays, in vivo tumor growth delay studies.

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David Vossen

Bioinformatician

Experience

As a bioinformatician I am embedded in both the Vens-Verheij and Wessels groups. I am working on a head and neck squamous cell carcinoma project, where the main objective is to identify deleterious mutations in DNA repair pathways.

 

 

 

 

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Floot, Ben

Ben Floot

Technician

Experience

From 1976 I worked as a technician in the NKI and in 1997 I joined the group of Fiona Stewart.
My work mainly involves studying the effects of local irradiation on normal tissues in mice. However, I have also studied effects of radiation and chemotherapy on tumor growth in mice and on different cell-types in vitro.
Techniques I have used include: colony forming and cell growth assays, tumor implantation and growth studies in mice, various surgical operation techniques, genotyping, immunohistochemistry and various analytical techniques (HPLC, AAS, IHC, ELISA, qPCR, Western blotting) on blood, urine or tissues dissected from mice.

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Rosemarie de Haan

Ph.D. student

Experience

My PhD project involves clinical and translational research. The main goal is to determine the safety and tolerability of olaparib (a PARP inhibitor) combined with radiotherapy in different groups of patients: non-small-cell lung cancer, head and neck squamous cell carcinoma and breast cancer patients. PARP is involved in single strand DNA repair. PARP inhibition leads to radiosensitization through the conversion of irradiation induced single strand DNA breaks into for the cell lethal double strand DNA breaks upon replication.

The translational research includes pharmacokinetic and pharmacodynamic analysis within the trial; as well as some in vitro cell culture studies.

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Essers, Paul

Paul Essers

Postdoc

Experience

I am a biologist turned bioinformatician in the Vens-Verheij group. I use gene expression data to predict treatment response and discover tumor subtypes in head and neck squamous cell carcinoma. My project is embedded in the ARTFORCE trial.

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Research updates View All Updates

  • Targeted radiosensitization in the clinic

    Recently, the first clinical study evaluating the safety and tolerability of the PARP inhibitor Olaparib in combination with (chemo-) radiotherapy has started in locally advanced non-small cell lung cancer.

  • Improved drug delivery

    The clinical introduction of our patented concept of liposomal co-formulated GC and doxorubicin (GC-LipoDox®) has been funded by the Dutch Cancer Society, NWO and STW.

Key publications View All Publications

  • Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis.

    Nature. 1996; 380: 75-79

    Verheij M, Bose R, Lin XH, Yao B, Jarvis WD, Grant S, Birrer MJ, Szabo E, Zon LI, Kyriakis JM, Haimovitz-Friedman A, Fuks Z, Kolesnick et al.

    Link to PubMed
  • Phosphoinositide phosphatase SHIP-1 regulates apoptosis induced by edelfosine, Fas ligation and DNA damage in mouse lymphoma cells.

    Biochem J. 2011; 440(1): 127-135.

    Alderliesten MC, Klarenbeek JB, van der Luit AH, van Lummel M, Jones DR, Zerp S, Divecha N, Verheij M, van Blitterswijk WJ.

    Link to PubMed
 
 

Recent publications View All Publications

  • Targeted Radiosensitization by the Chk1 Inhibitor SAR-020106

    Int J Radiat Oncol Biol Phys. 2013; 85(4): 1110-1118

    Borst GR, McLaughlin M, Kyula JN, Neijenhuis S, Khan A, Good J, Zaidi S, Powell NG, Meier P, Collins I, Garrett MD, Verheij M, Harrington...

    Link to PubMed
  • Differences in outcomes of oesophageal and gastric cancer surgery across Europe.

    Br J Surg. 2013; 100: 83-94.

    Dikken JL, van Sandick JW, Allum WH, Johansson J, Jensen LS, Putter H, Coupland VH, Wouters MW, Lemmens VE, van de Velde CJ, van der...

    Link to PubMed
 

Contact

  • Office manager

    Mariet van den Berg

  • E-mail

    ma.vd.berg@nki.nl

  • Telephone Number

    +31 20 512 9184

Van den Berg, Mariet

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