Department of Hematology Amsterdam UMC
Richard WJ Groen, PhD
Our research focuses on the investigation of the bidirectional interaction of tumor cells and the bone marrow (BM) microenvironment.
Dissecting the role of the BM microenvironment in hematological malignancies.
It is well established that the BM microenvironment plays an essential role of the in development, maintenance, and progression of hematological cancers. To study the interactions in the BM we have previously developed the "humanized" BM-like scaffold (huBMsc) model (Groen et al. Blood 2012), which was initially used to study patient-derived multiple myeloma (MM) cells, and now has proven to be suitable for other hematologic malignancies (AML, CML, and T-ALL) and to simulate bone metastatic lesions of solid tumors. Currently, we are studying the effect of incorporating human endothelial cells and the in vivo development of human vessels on the engraftment potential of hematological malignancies.
Overcoming MM-induced bone disease through osteogenic induction.
MM is characterized by osteolytic lesions in up to 80% of patients, being a major cause of morbidity. MM-induced bone disease is a result of decreased osteoblastic activity and increased osteoclastic activity. Even when suppressing osteoclasts with bisphosphonates or in the absence of disease activity bone lesions remain, probably due to the longstanding suppression of BM stromal cells (BMSCs). Therefore, there is an unmet need for therapeutics aiming to induce osteogenic differentiation of BMSCs. Recently, using the huBMsc model, we have characterized the molecular impact of MM cells on osteogenic differentiation and confirmed established disease biomarkers as well as identified novel mediators of MM disease progression and bone disease. Currently, we are investigating the functional and therapeutic implications of these MM-induced changes in stromal cells using genetically manipulated induced pluripotent stem cell (iPSC) lines that are differentiated in stromal cells (iMSCs).
Efficacy evaluation of novel pharmacological and cellular combination therapy for hematological malignancies.
Through our in vitro and in vivo bioluminescent imaging-based models for hematological malignancies, we facilitate the evaluation of novel pharmacological and cellular therapies targeting these malignancies for other members of the department, external academic collaborators, or pharmaceutical companies.
The Groen lab is grateful for having received research funding from Dutch Cancer Society (KWF), Stichting Leukemie.nl, European Commission (Marie Skłodowska-Curie Fellowship) Leukemia & Lymphoma Society, National Institutes of Health (NIH/R01), Worldwide Cancer Research and its collaborations with the pharmaceutical companies Johnson and Johnson, Genmab, Onkimmune, Gadeta, and Takeda.
Members of the group
Jiaxian Wang MSc | PhD-student
Ruud Ruiter | technician
Thomas Baardemans | technician
Bioluminescent images of vehicle and daratumumab-treated T-ALL engrafted huBMsc mice
Dr. Groen studied Pharmacochemistry at the VU University Amsterdam. After pursuing a PhD in the laboratory of Prof. Dr. Pals at the Academic Medical Center in Amsterdam, where he investigated the microenvironmental regulation of multiple myeloma (MM). He continued his studies on myeloma at the University Medical Center Utrecht (Dr. Martens and Prof. Dr. Lokhorst) and through a individual Marie Skłodowska-Curie Fellowship in the laboratory of Dr. Constantine Mitsiades at the Dana-Farber Cancer Institute. During this period, he developed the "humanized" bone marrow-like scaffold model, which has proven to be suitable to study not only patient-derived MM cells but also other hematologic malignancies as well as to simulate bone metastatic lesions of solid tumors. An achievement that resulted in the acceptance to the prestigious Translational Research Training in Hematology (TRTH), a joint effort of the European Hematology Association (EHA) and the American Society of Hematology (ASH). In 2015, Dr. Groen joined the MM program of VU University Medical Center (headed by Prof. Dr. Zweegman) as Assistant Professor, where he now utilize this model to study the influence of the BM microenvironment on tumor progression and therapy resistance, and to inform the design of novel pharmacological and cellular therapies targeting these malignancies.
Reconstructing the human hematopoietic niche in immunodeficient mice: opportunities for studying primary multiple myeloma.
Blood. 2012 Jul 19;120(3):e9-e16.
Groen RW, Noort WA, Raymakers RA, Prins HJ, Aalders L, Hofhuis FM, Moerer P, van Velzen JF, Bloem AC, van Kessel B, Rozemuller H, van Binsbergen E, Buijs A, Yuan H, de Bruijn JD, de Weers M, Parren PW, Schuringa JJ, Lokhorst HM, Mutis T, Martens AC.
Establishing human leukemia xenograft mouse models by implanting human bone marrow-like scaffold-based niches.
Blood. 2016 Dec 22;128(25):2949-2959.
Antonelli A, Noort WA, Jaques J, de Boer B, de Jong-Korlaar R, Brouwers-Vos AZ, Lubbers-Aalders L, van Velzen JF, Bloem AC, Yuan H, de Bruijn JD, Ossenkoppele GJ, Martens AC, Vellenga E, Groen RW *, Schuringa JJ *.
CD38 as a therapeutic target for adult acute myeloid leukemia and T-cell acute lymphoblastic leukemia.
Haematologica. 2019 Mar;104(3):e100-e103.
Naik J, Themeli M, de Jong-Korlaar R, Ruiter RWJ, Poddighe PJ, Yuan H, de Bruijn JD, Ossenkoppele GJ, Zweegman S, Smit L, Mutis T, Martens ACM, van de Donk NWCJ, Groen RWJ.
Liposomal dexamethasone inhibits tumor growth in an advanced human-mouse hybrid model of multiple myeloma.
J Control Release. 2019 Feb 28;296:232-240.
Deshantri AK, Fens MH, Ruiter RWJ, Metselaar JM, Storm G, van Bloois L, Varela-Moreira A, Mandhane SN, Mutis T, Martens ACM, Groen RWJ, Schiffelers RM.
Preclinical evidence for an effective therapeutic activity of FL118, a novel survivin inhibitor, in patients with relapsed/refractory multiple myeloma.
Haematologica. 2019 May 23.
Holthof LC, van der Horst HJ, van Hal-van Veen SE, Ruiter RWJ, Li F, Buijze M, Andersen MN, Yuan H, de Bruijn J, van de Donk NWCJ, Lokhorst HM, Zweegman S, Groen RWJ *, Mutis T *.
Bone Morphogenetic Protein 4 Gene Therapy in Mice Inhibits Myeloma Tumor Growth, But Has a Negative Impact on Bone.
JBMR Plus. 2019 Nov 22;4(1):e10247.
Westhrin M, Holien T, Zahoor M, Moen SH, Buene G, Størdal B, Hella H, Yuan H, de Bruijn JD, Martens A, Groen RW, Bosch F, Smith U, Sponaas AM, Sundan A, Standal T.