Short Biosketch PI
Eric Eldering was trained as molecular biologist/biochemist at the University of Amsterdam (PhD 1992). His research group at the Department of Experimental Immunology was formed in 2002, and he became Professor of Molecular Immuno-Hematology in 2012. Initially studying apoptosis regulation in normal and pathological immune cells, this had expanded to include wider fundamental and translational aspects in Immuno-Hematology, with focus on Chronic Lymphocytic Leukemia (CLL).
The group is currently led together with hematologist Arnon Kater, and is positioned as the foremost CLL center in the Netherlands, and is internationally well recognized. We maintain a biobank of CLL and other B cell malignancies. We regularly partner with pharmaceutical companies in collaborative projects to investigate novel anti-cancer drugs.
Focus of Research
Apoptosis, or programmed cell death, is of crucial importance in the immune system and in cancer, and remains a pillar of our research. We study Bcl-2 family members in B cell malignancies, novel drugs such as kinase inhibitors and BH3 mimetics, and drug resistance mechanisms.
In recent years, we shifted towards immunometabolism, with focus on the intrinsic metabolic changes in CLL as well as the impact of malignant cells on (CAR) T cell function and metabolism.
We study four interrelated areas (+ collaborations):
a) CLL genetics and molecular diagnostics (Dept of Clinical Genetics)
b) The leukemic microenvironment and novel drugs (Dept of Pathology - LYMMCARE)
c) Interaction between the immune system and CLL (Dept of Hematology - VUmc)
d) Metabolism and cell stress in B cell malignancies (Lab of Genetic Metabolic Diseases)
Latest grant
TKI-IXA grant 2021 CLOSIT CLL Lymph node Organoids for Screens and Intelligent Testing - With bioinformatician dr Perry Moerland from Dept. of Epidemiology and Data Science, partners Astra Zeneca and Bristol Myers Squibb. Project aims to develop 3D CLL organoids to faithfully mimic the leukemic microenvironment in CLL patient's lymh nodes, and provide a scalable platform for full molecular characterization, drug screens and AI-based modeling.
Groupmembers
Several of our PhD students are members of (inter)national consortia, as indicated.
Faculty
Prof. dr. Eric Eldering PhD (photo)
Prof. dr. Arnon P. Kater MD PhD
Postdocs
Fleur Peters PhD
Helga Simon Molas PhD
Marco Haselager PhD
Armando van Bruggen PhD
PhD Students recently graduated
Anne Martens (PhD Jan 2022)
Francesca Favaro (METACAN - https://www.metacan.eu/) (PhD May 24 2023)
Karoline Kielbassa MSc. - (Target to B! - https://www.target-to-b.nl/about/) (PhD Oct 13 2023)
Current PhD students
Chaja Jacobs MD
Chiara Montironi (METACAN - https://www.metacan.eu/)
Demi Both
Elena Camerini
Nienke Goedhart
Zhenghao Chen
Research technicians
Ingrid Derks
Joanne Rietveld
Gaspard Cretenet
Jamie Lee Roos
Marjolein Dijkema
Morris Mes (partly based at VUmc location)
Biobank technicians
Dennis de Rooij
Ilse Ligtenberg
Bianca van Driel
Ilona Twickler (partly based at VUmc location)
Biobank coordinator
Julie Dubois MD PhD
10 recent publications - (former) group members in BOLD
1. In Vitro 3D Spheroid Culture System Displays Sustained T Cell-dependent CLL Proliferation and Survival. Haselager MV, van Driel BF, Perelaer E, de Rooij D, Lashgari D, Loos R, Kater AP, Moerland PD, Eldering E. Hemasphere. 2023 Aug 23;7(9):e938. doi: 10.1097/HS9.0000000000000938. eCollection 2023 Sep
2. T-cell dysfunction by pseudohypoxia and autocrine purinergic signaling in chronic lymphocytic leukemia. Montironi C, Jacobs CF, Cretenet G, Peters FS, Schomakers BV, van Weeghel M, Kater AP, Simon-Molas H, Eldering E. Blood Adv. 2023 Aug 8: bloodadvances.2023010305. doi: 10.1182/bloodadvances.2023010305.
3. Electron transport chain and mTOR inhibition synergistically decrease CD40 signaling and counteract venetoclax resistance in chronic lymphocytic leukemia. Chen Z, Cretenet G, Carnazzo V, Simon-Molas H, Kater AP, Windt GJWV, Eldering E. Haematologica. 2023 Jul 13. doi: 10.3324/haematol.2023.282760.
4. Ibrutinib sensitizes CLL cells to venetoclax by interrupting TLR9-induced CD40 upregulation and protein translation. Kielbassa K, Haselager MV, Bax DJC, van Driel BF, Dubois J, Levin MD, Kersting S, Svanberg R, Niemann CU, Kater AP, Eldering E. Leukemia. 2023 Jun;37(6):1268-1276.
5. Negligible role of TRAIL death receptors in cell death upon endoplasmic reticulum stress in B-cell malignancies. Favaro F, Both D, Derks IAM, Spaargaren M, Muñoz-Pinedo C, Eldering E.
Oncogenesis. 2023 Feb 8;12(1):6.
6. JAK-STAT signalling shapes the NF-κB response in CLL towards venetoclax sensitivity or resistance via Bcl-XL. Haselager MV, Thijssen R, Bax D, Both D, De Boer F, Mackay S, Dubois J, Mellink C, Kater AP, Eldering E.
Mol Oncol. 2022 Dec 22. doi: 10.1002/1878-0261.13364. Online ahead of print.
7. SMG1, a nonsense-mediated mRNA decay (NMD) regulator, as a candidate therapeutic target in multiple myeloma. Leeksma AC, Derks IAM, Garrick B, Jongejan A, Colombo M, Bloedjes T, Trowe T, Leisten JC, Howarth M, Malek M, Mortensen DS, Blease K, Groza MC, Narla RK, Loos R, Kersten MJ, Moerland PD, Guikema JEJ, Kater AP, Eldering E, Filvaroff EH.
Mol Oncol. 2023 Feb;17(2):284-297.
8. Characterization of metabolic alterations of chronic lymphocytic leukemia in the lymph node microenvironment. Chen Z, Simon-Molas H, Cretenet G, Valle-Argos B, Smith LD, Forconi F, Schomakers BV, van Weeghel M, Bryant DJ, van Bruggen JAC, Peters FS, Rathmell JC, van der Windt GJW, Kater AP, Packham G, Eldering E.
Blood. 2022 Aug 11;140(6):630-643.
9. Combined ibrutinib and venetoclax treatment vs single agents in the TCL1 mouse model of chronic lymphocytic leukemia. Kater AP, Slinger E, Cretenet G, Martens AW, Balasubramanian S, Leverson JD, Eldering E. Blood Adv. 2021 Dec 14;5(23):5410-5414.
10. Regulation of Bcl-XL by non-canonical NF-κB in the context of CD40-induced drug resistance in CLL. Haselager M, Thijssen R, West C, Young L, Van Kampen R, Willmore E, Mackay S, Kater A, Eldering E.
Cell Death Differ. 2021 May;28(5):1658-1668.