Immuno-Hematology

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)

News

Recent 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

Faculty
Prof. dr. Eric Eldering PhD
Prof. dr. Arnon P.Kater MD PhD

Postdocs
Fleur Peters PhD
Helga Simon Molas PhD
Sanne Tonino MD PhD

PhD Students
Anne Martens MSc
Armando van Bruggen MSc
Chaja Jacobs MD MSc
Chiara Monitironi MSc (METACAN - https://www.metacan.eu/)
Eirini Deligianni MSc
Francesca Favaro MSc (METACAN - https://www.metacan.eu/)
Karoline Kielbassa MSc. - (Target to B! - https://www.target-to-b.nl/about/)
Marco Haselager MSc
Zhenghao Chen MSc

Research technicians
Ing. Ingrid Derks
Joanne Rietveld
Gaspard Cretenet
Bianca van Driel

Biobank technicians
Dennis de Rooij
Ilse Ligtenberg
Antoinet Schoonderwoerd

Biobank coordinator
Julie Dubois MD PhD

Key publications of last 5 years

1: Haselager M, Thijssen R, West C, Young L, Van Kampen R, Willmore E, Mackay S, Kater A, Eldering E. Regulation of Bcl-XL by non-canonical NF-κB in the context of CD40-induced drug resistance in CLL. Cell Death Differ. 2021 May;28(5):1658-1668. PMID: 33495554; PMCID: PMC8167103.

2: Haselager MV, Kielbassa K, Ter Burg J, Bax DJC, Fernandes SM, Borst J, Tam C, Forconi F, Chiodin G, Brown JR, Dubois J, Kater AP, Eldering E. Changes in Bcl-2 members after ibrutinib or venetoclax uncover functional hierarchy in determining resistance to venetoclax in CLL. Blood. 2020 Dec 17;136(25):2918-2926. PMID: 32603412.

3: Hofland T, de Weerdt I, Ter Burg H, de Boer R, Tannheimer S, Tonino SH, Kater AP, Eldering E. Dissection of the Effects of JAK and BTK Inhibitors on the Functionality of Healthy and Malignant Lymphocytes. J Immunol. 2019 Oct 15;203(8):2100-2109. PMID: 31511358.

4: Slinger E, Thijssen R, Kater AP, Eldering E. Targeting antigen-independent proliferation in chronic lymphocytic leukemia through differential kinase inhibition. Leukemia. 2017 Dec;31(12):2601-2607. PMID: 28462919.

5: van Attekum MHA, Terpstra S, Slinger E, von Lindern M, Moerland PD, Jongejan A, Kater AP, Eldering E. Macrophages confer survival signals via CCR1-dependent translational MCL-1 induction in chronic lymphocytic leukemia. Oncogene. 2017 Jun 29;36(26):3651-3660. PMID: 28192408; PMCID: PMC5584520.

6: Wensveen FM, Slinger E, van Attekum MH, Brink R, Eldering E. Antigen-affinity controls pre-germinal center B cell selection by promoting Mcl-1 induction through BAFF receptor signaling. Sci Rep. 2016 Oct 20;6:35673. PMID: 27762293; PMCID: PMC5071843.

7: Peperzak V, Slinger E, Ter Burg J, Eldering E. Functional disparities among BCL-2 members in tonsillar and leukemic B-cell subsets assessed by BH3-mimetic profiling. Cell Death Differ. 2017 Jan;24(1):111-119. PMID: 27689871; PMCID: PMC5260491.

8: Thijssen R, Ter Burg J, Garrick B, van Bochove GG, Brown JR, Fernandes SM, Rodríguez MS, Michot JM, Hallek M, Eichhorst B, Reinhardt HC, Bendell J, Derks IA, van Kampen RJ, Hege K, Kersten MJ, Trowe T, Filvaroff EH, Eldering E, Kater AP. Dual TORK/DNA-PK inhibition blocks critical signaling pathways in chronic lymphocytic leukemia. Blood. 2016 Jul 28;128(4):574-83. PMID: 27235137.

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