“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.

RESEARCH FOCUS:
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.

RESEARCHER'S BRIEF:
“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.