Projects per year
“We are exploring the interactions between malignant B cells and their microenvironment since these represent the Achilles’ heel of these cancers”
Professor dr S.T. Pals (Steven) MD, PhD
KEY KNOWLEDGE AREAS:
Malignant lymphoma, Multiple Myeloma (Kahler's disease), Lymphocyte homing, Adhesion molecules, Intracellular signalling.
The research themes of the Immuno- and Hematopathology laboratory are “B-cell development and neoplasia” and “Cell adhesion and migration in inflammation and cancer”. Our mission is: i) to advance the insight into the fundamental biological processes underlying B cell development and cell migration; ii) to acquire knowledge required to improve the diagnosis and treatment of B cell malignancies and to control inflammation and cancer metastasis.
CLINICAL AND INDUSTRY RELEVANCE:
Malignant Lymphoma and Multiple Myeloma are common cancers with a high patient morbidity and mortality. Genetic defects in concert with cues from the tumor microenvironment activate signalling pathways that drive tumor growth, survival, and dissemination. Targeting these pathways by small-molecule drugs and antibodies has recently been shown to be highly effective in Lymphoma and Myeloma treatment. In our laboratory, new targets are being explored by in vitro studies as well as in by employing mouse models.
“In the past, workers in a Pathology department like ours would visually inspect patient tissue for signs of disease. Now we are actually delving into the molecular details of pathologies, lymphoma and multiple myeloma in our case. Some very complex and highly interesting details are coming to light. We know now that both normal and malignant B cells require 'homing receptors' to direct them to specific tissues or organs, where they recognize ‘address molecules’. Once arrived, the B cells are highly dependent on the microenvironment for their growth and survival; we are exploring which environmental cues are crucial. We thusfar discovered that WNTs and hepatocyte growth factor (HGF) support Multiple Myeloma growth, and also promote the bone damage typically seen in this disease. Moreover, recent studies from our laboratory have shown that interfering with the homing and retention of malignant B cells is a highly effective treatment for patients with several types of non-Hodgkin's lymphoma, including chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and Waldestrom Macroglobilinemia. Specifically, we demonstrated that the impressive therapeutic effect of the "break through" Bruton's tyrosine kinase (BTK) inhibitor ibrutinib and the PI3Kd inhibitor idelalisib is largely based on induction of cell death by anoikis (homelessness).
RESEARCHER'S QUALIFICATIONS, EXPERIENCE:
Professor of Immuno- and Hematopathology. MD, PhD, Head Molecular Immuno- and Hematopathology laboratory. STP is member of the Scientific Board of the Dutch Cancer Society, and the Scientific Advisory Board for the Fight against Cancer of the Royal Dutch Academy of Science.
Expertise related to UN Sustainable Development Goals
In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):
Collaborations and top research areas from the last five years
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Aberrantly expressed LGR4 empowers Wnt signaling in multiple myeloma by hijacking osteoblast-derived R-spondinsvan Andel, H., Ren, Z., Koopmans, I., Joosten, S. P. J., Kocemba, K. A., de Lau, W., Kersten, M. J., de Bruin, A. M., Guikema, J. E. J., Clevers, H., Spaargaren, M. & Pals, S. T., 2017, In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 114, 2, p. 376-381
Research output: Contribution to journal › Article › Academic › peer-review27 Citations (Scopus)
Loss of CYLD expression unleashes Wnt signaling in multiple myeloma and is associated with aggressive diseasevan Andel, H., Kocemba, K. A., de Haan-Kramer, A., Mellink, C. H., Piwowar, M., Broijl, A., van Duin, M., Sonneveld, P., Maurice, M. M., Kersten, M. J., Spaargaren, M. & Pals, S. T., 2017, In: Oncogene. 36, 15, p. 2105-2115
Research output: Contribution to journal › Article › Academic › peer-review35 Citations (Scopus)
MET Signaling Mediates Intestinal Crypt-Villus Development, Regeneration, and Adenoma Formation and Is Promoted by Stem Cell CD44 IsoformsJoosten, S. P. J., Zeilstra, J., van Andel, H., Mijnals, R. C., Zaunbrecher, J., Duivenvoorden, A. A. M., van de Wetering, M., Clevers, H., Spaargaren, M. & Pals, S. T., 2017, In: Gastroenterology. 153, 4, p. 1040-+
Research output: Contribution to journal › Article › Academic › peer-review34 Citations (Scopus)
High prevalence of oncogenic MYD88 and CD79B mutations in primary testicular diffuse large B-cell lymphomaKraan, W., van Keimpema, M., Horlings, H. M., Schilder-Tol, E. J. M., Oud, M. E. C. M., Noorduyn, L. A., Kluin, P. M., Kersten, M. J., Spaargaren, M. & Pals, S. T., 2014, In: Leukemia. 28, 3, p. 719-720
Research output: Contribution to journal › Comment/Letter to the editor › Academic80 Citations (Scopus)
The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemiade Rooij, M. F. M., Kuil, A., Geest, C. R., Eldering, E., Chang, B. Y., Buggy, J. J., Pals, S. T. & Spaargaren, M., 2012, In: Blood. 119, 11, p. 2590-2594
Research output: Contribution to journal › Article › Academic › peer-review455 Citations (Scopus)