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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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Conchita Vens Ph.D.

Senior scientist

Experience

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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 RN.

    .

    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 KJ..

    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 Geest LG, Larsson HJ, Cats A, Verheij M.

    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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