Department of Hematology Amsterdam UMC
location VUmc
Richard WJ Groen, PhD
Our research focuses on the investigation of the bidirectional interaction of tumor cells and the bone marrow (BM) microenvironment.
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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.
Financial Support
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
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Bing Li | PhD-student
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Alejandro Holtmann | PhD-student
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Jiaxian Wang | PhD-student
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Ruud Ruiter | technician
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Thomas Baardemans | technician
Bioluminescent images of vehicle and daratumumab-treated T-ALL engrafted huBMsc mice
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.
Combining a CAR and a chimeric costimulatory receptor enhances T cell sensitivity to low antigen density and promotes persistence.
Sci Transl Med. 2021 Dec 8;13(623):eabh1962.
Katsarou A, Sjöstrand M, Naik J, Mansilla-Soto J, Kefala D, Kladis G, Nianias A, Ruiter R, Poels R, Sarkar I, Patankar YR, Merino E, Reijmers RM, Frerichs KA, Yuan H, de Bruijn J, Stroopinsky D, Avigan D, van de Donk NWCJ, Zweegman S, Mutis T, Sadelain M, Groen RWJ, Themeli M.
Bone Marrow Mesenchymal Stromal Cells Can Render Multiple Myeloma Cells Resistant to Cytotoxic Machinery of CAR T Cells through Inhibition of Apoptosis.
Clin Cancer Res. 2021 Jul 1;27(13):3793-3803.
Holthof LC, van der Schans JJ, Katsarou A, Poels R, Gelderloos AT, Drent E, van Hal-van Veen SE, Li F, Zweegman S, van de Donk NWCJ, Themeli M, Groen RWJ, Mutis T.
Genome-scale functional genomics identify genes preferentially essential for multiple myeloma cells compared to other neoplasias.
Nat Cancer. 2023 May;4(5):754-773.
de Matos Simoes R, Shirasaki R, Downey-Kopyscinski SL, Matthews GM, Barwick BG, Gupta VA, Dupéré-Richer D, Yamano S, Hu Y, Sheffer M, Dhimolea E, Dashevsky O, Gandolfi S, Ishiguro K, Meyers RM, Bryan JG, Dharia NV, Hengeveld PJ, Brüggenthies JB, Tang H, Aguirre AJ, Sievers QL, Ebert BL, Glassner BJ, Ott CJ, Bradner JE, Kwiatkowski NP, Auclair D, Levy J, Keats JJ, Groen RWJ, Gray NS, Culhane AC, McFarland JM, Dempster JM, Licht JD, Boise LH, Hahn WC, Vazquez F, Tsherniak A, Mitsiades CS.