R.W. (Rudi) Hendriks, Professor, PhD

With a fundamental background in signal transduction and gene regulation in lymphocyte differentiation, I started as head of the Pulmonary Medicine Research Laboratory at the Erasmus MC, in October 2007. The key objective of my translational research program is the identification of molecular mechanisms underlying the function of lymphocytes in health and their role in the pathogenesis of respiratory diseases. It comprises complementary immunological and molecular in vitro and in vivo approaches to gain knowledge that is required to address major unmet needs in the treatment of inflammatory disorders of the lung.

Through the generation of several mouse models (supported by a Royal Netherlands Academy of Arts and Sciences Fellowship) and analyses of patient material, we explore how B-cell receptor signaling – particularly activation of Bruton’s tyrosine kinase - contributes to B-cell differentiation, malignancies, autoimmunity and interstitial lung disease (ILD). This research is strongly embedded in the (inter)national B cell research community, involves collaboration with industry and has been supported by grants from ZonMW, The Dutch Cancer society and the Netherlands Arthritis Foundation. In this field, I’m active as a board member of the European B cell (EBC) Network and co-organizer of the EBC Summer School and EBC international conferences.  

A second, closely related, research line concerns the pathogenic roles of T cell subsets and type 2 innate lymphoid cells in various inflammatory lung diseases, including sarcoidosis and allergic asthma. These studies, funded by several grants from the Netherlands Lung Foundation, are focused on signal transduction pathways and transcription factors controlling lymphocyte identity and function. To optimize the translational impact of this research program, we (i) use physiologically relevant (e.g. house dust-mite driven) asthma animal models and (ii) study patient material, whereby our research benefits from a longstanding close collaboration with pulmonologists at Erasmus MC (sarcoidosis, ILD) and the Franciscus Gasthuis peripheral hospital (asthma). I’m active in the Netherlands Respiratory Society, e.g. as co-organiser of the yearly Advanced Technology in Lung Research symposium. Finally, I contribute to the Erasmus MC Infection and Immunity Research Master program as well as immunology courses and symposia for PhD students.

 

Description of research lines

The research laboratory of the Department of Pulmonary Medicine focuses on fundamental, translational and clinical research concerning the pathology of various respiratory disorders. In this context, the research interests include the differentiation program of lymphoid cells in health and disease, using molecular approaches and animal models. The aims comprise the characterization of signal transduction pathways and lymphoid-specific transcription factors that implement cell fate decisions at specific checkpoints. One the one hand, T and B cells are studied in a range of respiratory disorders, including sarcoidosis, lung fibrosis and community-acquired pneumonia. There is also a specific focus on Th2 cells - along with innate lymphoid cells - in type II immunity, both in mouse models for allergic airway inflammation and in patients with allergic asthma in a longstanding close collaboration with physicians at the Franciscus Gasthuis Rotterdam. On the other hand, B cell receptor signaling is an important topic, particularly the role of Bruton’s tyrosine kinase (BTK), both in B cell differentiation and in autoimmune inflammation and interstitial lung disease (ILD).

 

 Principal Investigators

 

• Ralph Stadhouders
• Odilia Corneth

 

Prof. dr. Rudi Hendriks studied Biology at the University of Utrecht, the Netherlands, and did his PhD studies on X chromosome inactivation patterns in human X-linked immunodeficiency diseases in the Department of Immunohaematology at the Leiden University Medical Center (Prof. J.J. van Rood; Dr. R.K.B. Schuurman) in 1991. After a post-doctoral training in the Genetics Laboratory of the University of Oxford, UK, where he studied genetic aspects of X chromosome inactivation, he started his own line of lymphoctye research within the lab of Prof. Frank Grosveld at the Department of Cell Biology and Genetics of the Erasmus MC Rotterdam, the Netherlands. In 1999 he moved his group to the Department of Immunology at the Erasmus MC, where he continued his research on the developmental program of lymphocytes in relation to immunodeficiency diseases and leukemia. Since 2007 Dr. Rudi W. Hendriks is head of the Pulmonary Medicine Research Laboratory. His research is focused on the role of B, T and innate lymphocytes in pulmonary immunity, in particular in allergic airway inflammation and autoimmune processes in the lung.  He is active as active as a board member of the European B cell (EBC) Network and co-organizer of the EBC Summer School and international conferences.  

• Gay ACA, Banchero M, Carpaij O, Kole TM, Apperloo L, van Gosliga D, Fajar PA, Koppelman GH, Bont L, Hendriks RW, van den Berge M, Nawijn MC (2024). Airway epithelial cell response to RSV is mostly impaired in goblet and multiciliated cells in asthma. Thorax 79:811. 
• Van der Ploeg EK, Krabbendam L, Vroman H, van Nimwegen M, de Bruijn MJW, de Boer GM, Bergen IM, Kool M, Tramper-Standers GA, Braunstahl GJ, Huylebroeck D, Hendriks RW*, Stadhouders R* (2023).  Type-2 CD8⁺ T-cell formation relies on interleukin-33 and is linked to asthma exacerbations. Nat Comm 14: 5137.
• Stikker BS, Stik G, van Ouwerkerk AF, Trap L, Spicuglia S, Hendriks RW, Stadhouders R (2022). Severe COVID-19-associated variants linked to chemokine receptor gene control in monocytes and macrophages. Genome Biol 23:96.
• Corneth OBJ, Neys SFH, Hendriks RW (2022) Aberrant B Cell Signaling in Autoimmune Diseases. Cells 11:3391.
• Heukels P, Corneth OBJ, van Uden D, van Hulst JAC, van den Toorn LM, van den Bosch AE, Wijsenbeek MS, Boomars KA, Kool M, Hendriks RW (2021). Loss of immune homeostasis in patients with idiopathic pulmonary arterial hypertension. Thorax 76:1209.
•  Van der Ploeg EK, Golebski K, van Nimwegen M, Fergusson JR, Heesters BA, Martinez-Gonzalez I, Kradolfer CMA, van Tol S, Scicluna BP, de Bruijn MJW, de Boer GM, Tramper-Stranders GA, Braunstahl GJ, van IJcken WFJ, Nagtegaal AP, van Drunen CM, Fokkens WJ, Huylebroeck D, Spits H, Hendriks RW, Stadhouders R, Bal SM (2021). Steroid-resistant human inflammatory ILC2s are marked by CD45RO and elevated in type 2 respiratory diseases. Sci Immuno. 6:eabd3489.
• Tindemans I, van Schoonhoven A, KleinJan A, de Bruijn MJ, Lukkes M, van Nimwegen M, van den Branden A, Bergen IM, Corneth OB, van IJcken WF, Stadhouders R*, Hendriks RW* (2020). Notch signaling licenses allergic airway inflammation by promoting Th2 cell lymph node egress. J Clin Invest 130:3576.
• Pal Singh S, Dammeijer F, Hendriks RW (2018). Role of Bruton's tyrosine kinase in B cells and malignancies. Mol Cancer 17:57.
•  Lim AI, Li Y, Lopez-Lastra S, Stadhouders R, Paul F, Casrouge A, Serafini N, Puel A, Bustamante J, Surace L, Masse-Ranson G, David E, Strick-Marchand H, Le Bourhis L, Cocchi R, Topazio D, Graziano P, Muscarella LA, Rogge L, Norel X, Sallenave JM, Allez M, Graf T, Hendriks RW, Casanova JL, Amit I, Yssel H, Di Santo JP (2017). Systemic Human ILC Precursors Provide a Substrate for Tissue ILC Differentiation. Cell 168:1086.
• Tindemans I, Serafini N, Di Santo JP and Hendriks RW (2014). GATA-3 function in innate and adaptive immunity. Immunity 41:191.

Current PhD students

Anne Onrust-Van Schoonhoven

Anneloes van Krimpen

Simone Olsthoorn

Lianne Trap

Bernard Stikker

Stefan Neys

Lieke de Jong

Jochem Weekers

Vicky Bogaard

Anne-Lotte Redel (Franciscus Gasthuis)

Cathelijne van Zelst (Franciscus Gasthuis)

Sanne van Deelen (Franciscus Gasthuis)

Marijn Berg (UMCG Groningen)

Alumni - PhD students

 

Claudia Ribeiro de Almeida; CTCF: A Crucial Regulator of Gene Expression in Lymphocytes

17th November 2010; http://repub.eur.nl/pub/21344

 

Van Ta; Role of Pre-B Cell Receptor Signaling Molecules in B Cell Differentiation and Tumor Suppression. 15th December 2010; http://repub.eur.nl/pub/22989

 

Bregje ten Berge; Dendritic Cells and T Lymphocytes in the Pathogenesis of Pulmonary Sarcoidosis

21st September 2011; http://repub.eur.nl/pub/26498

 

Marthe Paats; The T Helper 17 Lineage in Pulmonary Diseases cytokine analysis in local and systemic inflammation. 21st September 2012; http://repub.eur.nl/pub/37360

 

Anouk Gloudemans; Induction of Immunoglobulin A as a Therapeutic Intervention in Allergic Asthma

14th December 2012; http://repub.eur.nl/pub/38702

 

Roel Klein Wolterink; Stage-dependent Functions of GATA-3 in Lymphocyte Lineage Determination and Type-2 Immunity. 15th May 2013; http://repub.eur.nl/pub/40285

 

Marlies Heuvers; Improving Lung Cancer Survival Time to move on

11th June 2013; https://repub.eur.nl/pub/51629

 

Laurens Kil; Btk in Autoimmunity and leukemia: too much of a good thing?

3rd December 2013; http://repub.eur.nl/pub/50149

 

Adriaan van Beek; The aging immune system and dietary interventions.

18th January 2017; 392235 (wur.nl)

 

Caroline Broos; T helper 17 cells and Regulatory T cells in Pulmonary Sarcoidosis : It takes two to tangle. 31st March 2017; https://repub.eur.nl/pub/98472/

 

Lysanne Lievense; Macrophages in Mesothelioma : Improving immunotherapy in pulmonary oncology. 31st March 2017; https://repub.eur.nl/pub/98474

 

Heleen Vroman; Heterogeneity in asthma : Implications for dendritic cell activation?

23th June 2017 https://repub.eur.nl/pub/100318

 

Bobby Li; Group 2 Innate Lymphoid Cells in Allergic Airway Inflammation : Early Birds or Night Owls

9th February 2018; https://repub.eur.nl/pub/104292/

 

Irma Tindemans; Notch Signaling During T Helper 2 Cell-Mediated Inflammation in Allergic Asthma

22nd March 2018; https://repub.eur.nl/pub/105791

 

Kitty de Leur; T cell communication in kidney transplantation

2nd July 2019; https://repub.eur.nl/pub/117514

 

Simar Pal Singh; Signal Transduction Pathways in Chronic Lymphocytic Leukemia

29th October 2019; https://repub.eur.nl/pub/117514

 

Alice Muggen; Chronic Lymphocytic Leukemia: The B cell receptor and beyond

7th January 2020; https://repub.eur.nl/pub/122602

 

Pauline de Goeje; Immune Monitoring in Thoracic Malignancies.

4th February 2020; https://repub.eur.nl/pub/124272

 

Tridib Das; An act of balance: A20/TNFAIP3 in dendritic cells is essential to prevent autoimmunity

24th February 2021; https://repub.eur.nl/pub/117514

 

Jasper Rip; Bruton’s Tyrosine Kinase Signaling in Health and Disease; a molecular perspective

8th June 2021; https://repub.eur.nl/pub/135615

 

Floris Dammeijer; Immunity Unchained: Improving Cancer Immunotherapy by targeting the Tumor Macro-Environment. 5th October 2021; https://repub.eur.nl/pub/135707

 

Peter Heukels; Adaptive Immunity in Interstitial Lung Diseases and Pulmonary Hypertension

23rd November 2021; https://repub.eur.nl/pub/136997

 

Jelle Folkerts; Regulation of human mast cell Activation. 

1st June 2022;

 

Thomas Koudstaal; Dendritic cells and T cells in Pulmonary Hypertension.

2nd November 2022;

 

Denise van Uden; Adaptive Immunity in Different Pulmonary Hypertension Subgroups

1st November 2023; https://repub.eur.nl/pub/131576

 

Geertje de Boer; Wheezy lungs in the sneezy seasons of life

30 November 2023; 

 

Esmee van der Ploeg; Group 2 Innate Lymphoid Cells and Cytotoxic T cells in Type-2 Inflammatory Diseases. 29th February 2024;

 

Aurore Gay; Toward targeting the origin of the inflammatory cascade in asthma

19^th July 2024; pure.rug.nl/ws/portalfiles/portal/1040406698/Complete_thesis.pdf

 

Jelle Miedema: Adaptive Immune responses and treatment in sarcoidosis and pulmonary fibrosis

5^th November 2024

 

In house-dust-mite-induced allergic airway inflammation, we found that ILC2 activation required T cells. Thus, in HDM-mediated airway inflammation in mice ILC2s do not provide an early innate source of IL-5/IL-13. Furthermore, the activation status of ILC2s was increased following influenza virus infection in mice, thereby likely contributing to inflammation-induced asthma exacerbation. Epigenetic analyses indicated that in circulating ILC2s ~80% of asthma-associated genes from GWAS were active, supporting a role for ILC2 in human asthma. In acute and chronic mouse models of HDM-mediated allergic asthma, we found that expression of Notch and its nuclear effector RBPJκ in T cells is essential for disease development. Mice lacking Jagged1/2 on DCs, T cells or lymph node stromal cells still developed HDM-driven airway inflammation. Importantly, hallmarks of asthma could be suppressed by the Notch inhibitory peptide SAHM1, which interferes with RBPJκ function. We also observed an increase in surface Notch1 and Notch2 positive TH2 cells in peripheral blood of asthma patients. Concerning our B cell work, we recently found that BTK protein levels and phosphorylation were increased in B cells from anti-citrullinated protein antibody (ACPA)-positive patients with rheumatoid arthritis, in Sjögren’s syndrome and in idiopathic pulmonary arterial hypertension.