Brief summary of research over last five years

Leon Terstappen¬†is a medical doctor with a PhD in biophysics who is intrigued by finding technology solutions to medical problems. He has become¬†an international recognized expert in cytometry and pioneered the detection of rare cells. ¬†Early in his career he explored the differentiation pathways of hematopoietic cell lineages and identified the phenotype of the hematopoietic stem cell. With the observation of cancer cells in cell suspensions used for stem cell transplantation of breast cancer patients, he changed his focus and started his¬†pioneering work in Circulating Tumor Cells (CTC).¬†¬† He was in charge of the development of the CellSearch system, the only FDA cleared platform to enumerate CTC in blood. Using this technology, it was demonstrated that the presence of CTC in patients with no known metastatic disease are at high risk for disease recurrence. In patients with metastatic disease the CTC load is strongly associated with poor outcome and the strongest predictor of therapy response. His research efforts at the University of Twente focused on further¬†technology development to identify, isolate and characterize CTC in all patients with disseminated cancer and demonstration of the clinical utility of the developed tools through national and international collaborations with clinical research centers.¬†¬†Our[EMA(1]¬†¬†observation of small objects being present in blood of cancer patients and their load being strongly associated with clinical outcome lead to¬†the[EMA(2]¬†¬†interest in Extracellular Vesicles (EV).¬†We[EMA(3]¬†¬†baptized these objects as tumor derived EV (tdEV) and observed a large yet unexplained heterogeneity in appearance. Recently technology has been invented and developed to determine the secretome of individual CTC and assess their response to therapy. This is currently being explored in hormone sensitive metastatic prostate cancer through an NWO/KWF project in collaboration with Erasmus. The ultimate objective is to guide individual treatment of cancer patients throughout the course of their disease and along the way¬†validate the ‚Äúliquid biopsies‚ÄĚ technologies to truly enable personalized cancer care.

 In 2007, Terstappen started the department of Medical Cell BioPhysics at The University of Twente. From 1994 to 2007, he was Chief Scientific Officer at Immunicon Corporation, Huntingdon Valley, PA, USA. From 1987 to 1994, he held various research positions in the research department of Becton Dickinson Immunocytometry systems in Mountain View CA, USA. He obtained his PhD from the University of Twente and his medical degree from the University of Groningen, The Netherlands.

Expertise

  • Medicine and Dentistry

    • Circulating Tumor Cell
    • Patient
    • Cells
    • Neoplasm
    • Prostate Cancer
  • Biochemistry, Genetics and Molecular Biology

    • Sample
    • Overall Survival
    • Antibody

Organisations

Publications

2024
2023
Flow-based immunomagnetic enrichment of circulating tumor cells from diagnostic leukapheresis productMolecular oncology (E-pub ahead of print/First online). Stevens, M., Mentink, A., Coumans, F. A. W., Dathathri, E., Isebia, K. T., Kraan, J., de Wit, R., Martens, J. W. M. & Terstappen, L. W. M. M.https://doi.org/10.1002/1878-0261.13565Improving circulating tumor cell detection from diagnostic leukapheresis material: Getting the most out of it. University of Twente. Stevens, M.https://doi.org/10.3990/1.9789036559096A magnetic microneedle to isolate single immunomagnetically labeled cellsLab on a chip, 24(3), 460-466 (E-pub ahead of print/First online). Stevens, M., Harder, P. & Terstappen, L. W. M. M.https://doi.org/10.1039/d3lc00920cMeasuring antigen expression of cancer cell lines and circulating tumour cellsScientific reports, 13(1), Article 6051. Mentink, A., Isebia, K. T., Kraan, J., Terstappen, L. W. M. M. & Stevens, M.https://doi.org/10.1038/s41598-023-33179-yImproved enrichment of circulating tumor cells from diagnostic leukapheresis productCytometry. Part A, 103(11), 881-888. Stevens, M., Mentink, A., Nanou, A., Coumans, F. A. W., Isebia, K. T., Kraan, J., Hamberg, P., Martens, J. W. M. & Terstappen, L. W. M. M.https://doi.org/10.1002/cyto.a.24779Hepatocyte survival and proliferation by fibroblast growth factor 7 attenuates liver inflammation, and fibrogenesis during acute liver injury via paracrine mechanismsBiomedicine and Pharmacotherapy, 167, Article 115612. Geervliet, E., Terstappen, L. W. M. M. & Bansal, R.https://doi.org/10.1016/j.biopha.2023.115612Data from Comparing Circulating Tumor Cell Counts with Dynamic Tumor Size Changes as Predictor of Overall Survival: A Quantitative Modeling Framework. Netterberg, I., Karlsson, M. O., Terstappen, L. W. M. M., Koopman, M., Punt, C. J. A. & Friberg, L. E.https://doi.org/10.1158/1078-0432.c.6529016In Vivo Detection of Circulating Cancer-Associated Fibroblasts in Breast Tumor Mouse Xenograft: Impact of Tumor Stroma and ChemotherapyCancers, 15(4), Article 1127. Lu, T., Oomens, L., Terstappen, L. W. M. M. & Prakash, J.https://doi.org/10.3390/cancers15041127Tumor-Derived Extracellular Vesicles as Complementary Prognostic Factors to Circulating Tumor Cells in Metastatic Breast CancerJCO Precision Oncology, 7, Article e2200372. Nanou, A., Miao, J., Coumans, F. A. W., Dolce, E. M., Darga, E., Barlow, W., Smerage, J. B., Paoletti, C., Godwin, A. K., Pusztai, L., Sharma, P., Thompson, A., Hortobagyi, G. N., Terstappen, L. W. M. M. & Hayes, D. F.https://doi.org/10.1200/PO.22.00372Circulating Tumor Cells (CTC) and Tumor-Derived Extracellular Vesicles (tdEV)In Current Cancer Research (pp. 113-136). Springer Nature. Nanou, A., Beekman, P., Enciso Martinez, A. & Terstappen, L. W. M. M.https://doi.org/10.1007/978-3-031-22903-9_6Single Cell Secretome Analyses of Hepatic Stellate Cells: Aiming for Single Cell PhenomicsIn Hepatic Stellate Cells: Methods and Protocols (pp. 257-268). Humana Press. Booijink, R., Terstappen, L. & Bansal, R.https://doi.org/10.1007/978-1-0716-3207-9_16
2022
Characterizing Circulating Tumor Cells and Tumor-Derived Extracellular Vesicles in Metastatic Castration-Naive and Castration-Resistant Prostate Cancer PatientsCancers, 14(18), Article 4404. Isebia, K. T., Dathathri, E., Verschoor, N., Nanou, A., de Jong, A. C., Coumans, F. A. W., Terstappen, L. W. M. M., Kraan, J., Martens, J. W. M., Bansal, R. & Lolkema, M. P.https://doi.org/10.3390/cancers14184404StarDist Image Segmentation Improves Circulating Tumor Cell DetectionCancers, 14(12), Article 2916. Stevens, M., Nanou, A., Terstappen, L. W. M. M., Driemel, C., Stoecklein, N. H. & Coumans, F. A. W.https://doi.org/10.3390/cancers14122916Liquid Biopsy Based Circulating Biomarkers in Metastatic Prostate CancerFrontiers in oncology, 12, Article 863472. Dathathri, E., Isebia, K. T., Abali, F., Lolkema, M. P., Martens, J. W. M., Terstappen, L. W. M. M. & Bansal, R.https://doi.org/10.3389/fonc.2022.863472Karyotype diversification in colorectal cancer. University of Twente. Bollen, Y.https://doi.org/10.3990/1.9789036553506Leukapheresis increases circulating tumour cell yield in non-small cell lung cancer, counts related to tumour response and survivalBritish journal of cancer, 126, 409-418. Tamminga, M., Andree, K. C., van den Bos, H., Hiltermann, T. J. N., Mentink, A., Spierings, D. C. J., Lansdorp, P., Timens, W., Schuuring, E., Terstappen, L. W. M. M. & Groen, H. J. M.https://doi.org/10.1038/s41416-021-01634-0Efficient and error-free fluorescent gene tagging in human organoids without double-strand DNA cleavagePLoS Biology, 20(1), Article e3001527, 1-16. Bollen, Y., Hageman, J. H., van Leenen, P., Derks, L. L. M., Ponsioen, B., Buissant des Amorie, J. R., Verlaan-Klink, I., van den Bos, M., Terstappen, L. W. M. M., van Boxtel, R. & Snippert, H. J. G.https://doi.org/10.1371/journal.pbio.3001527MicroRNA in the Tumor Stroma: Diagnostic and Therapeutic ImplicationsIn The Tumor Stroma: Biology and Therapeutics. Jenny Stanford Publishing. Lu, T., Terstappen, L. W. M. M. & Prakash, J.https://doi.org/10.1201/9781003224921-8
2021
Measurement of the drug sensitivity of single prostate cancer cellsCancers, 13(23), Article 6083. Abali, F., Baghi, N., Mout, L., Broekmaat, J. J., Tibbe, A. G. J. & Terstappen, L. W. M. M.https://doi.org/10.3390/cancers13236083Dynamic changes of circulating tumor DNA predict clinical outcome in patients with advanced non-small-cell lung cancer treated with immune checkpoint inhibitorsJCO Precision Oncology, 5, 1540-1553. Weber, S., van der Leest, P., Donker, H. C., Schlange, T., Timens, W., Tamminga, M., Hasenleithner, S. O., Graf, R., Moser, T., Spiegl, B., Yaspo, M. L., Terstappen, L. W. M. M., Sidorenkov, G., Hiltermann, T. J., Speicher, M. R., Schuuring, E., Heitzer, E. & Groen, H. J. M.https://doi.org/10.1200/PO.21.00182Reconstructing single-cell karyotype alterations in colorectal cancer identifies punctuated and gradual diversification patternsNature genetics, 53(8), 1187-1195. Bollen, Y., Stelloo, E., van Leenen, P., van den Bos, M., Ponsioen, B., Lu, B., van Roosmalen, M. J., Bolhaqueiro, A. C. F., Kimberley, C., Mossner, M., Cross, W. C. H., Besselink, N. J. M., van der Roest, B., Boymans, S., Oost, K. C., de Vries, S. G., Rehmann, H., Cuppen, E., Lens, S. M. A., ‚Ķ Snippert, H. J. G.https://doi.org/10.1038/s41588-021-00891-2Presence and strength of binding of IgM, IgG and IgA antibodies against SARS-CoV-2 during CoViD-19 infectionBiosensors & bioelectronics, 183, Article 113165. Schasfoort, R. B. M., van Weperen, J., van Amsterdam, M., Parisot, J., Hendriks, J., Koerselman, M., Karperien, M., Mentink, A., Bennink, M., Krabbe, H., Terstappen, L. W. M. M. & Mulder, A. H. L.https://doi.org/10.1016/j.bios.2021.113165High throughput surface plasmon resonance imaging method for clinical detection of presence and strength of binding of IgM, IgG and IgA antibodies against SARS-CoV-2 during CoViD-19 infectionMethodsX, 8, Article 101432. Schasfoort, R. B. M., van Weperen, J., van Amsterdam, M., Parisot, J., Hendriks, J., Koerselman, M., Karperien, M., Mentink - Leusink, A., Bennink, M., Krabbe, H., Terstappen, L. W. M. M. & Mulder, A. H. L.https://doi.org/10.1016/j.mex.2021.101432

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University of Twente

Carré (building no. 15), room C4437
Hallenweg 23
7522 NH Enschede
Netherlands

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