About our research group/lab
Our research
Why was this group formed?
The lung is continuously exposed to the outside world and is a portal of entry for viral, bacterial, and fungal infection. Throughout evolution, an extensive defense mechanism has developed that protects humans from these potentially lethal assaults and at the same prevents reactivity to harmless antigens. Nevertheless, the incidence of lung diseases such as asthma and sarcoidosis has risen dramatically over the last 50 years. Moreover, the immune system is the body’s defense to malignancies, and conversely, immunotherapy is a promising modality to treat lung cancer.
What is the overall aim?
Our main aims are to:
- To study the molecular biology of the differentiation program of lymphocytes in the context of pulmonary inflammation. These studies include innate lymphoid cells and Th2 cells in asthma, Th17 cells in sarcoidosis, and B cells in interstitial lung disease and systemic autoimmunity.
- To elucidate how dendritic cells direct and maintain immune responses in the lung, particularly in asthma and various interstitial lung diseases.
- To develop dendritic-cell based immunotherapy in mesothelioma, a tumor caused by asbestos fiber inhalation, and to identify the role of various immunosuppressive cells present in the tumor microenvironment.
What type of research do you focus on in this group?
The research laboratory of the Dept Pulmonary Medicine focuses on clinical and translational research concerning the pathology of a wide range of respiratory disorders, including sarcoidosis, interstitial lung disease, asthma as well as lung cancer. In addition, the research program includes fundamental studies on the differentiation program of lymphoid cells in health and disease, using molecular approaches. Over the last years technical expertise has been acquired in animal models, using cellular immunology, multi-color flow cytometry, confocal microscopy, as well as molecular biology, genome-wide expression and epigenetic analyses.
Our projects
- Inflammation and remodeling in various interstitial lung diseases
(Mirjam Kool and Alex Kleinjan) - B lymphocytes in autoimmunity and interstitial lung diseases
(Odilia Corneth) - Functional epigenomics of lymphocyte activation
(Ralph Stadhouders) - Thoracic oncology and immunotherapy
(Heleen Vroman)
Key Publications
Broos CE, Koth LL, van Nimwegen M, In 't Veen JCCM, Paulissen SMJ, van Hamburg JP, Annema JT, Heller-Baan R, Kleinjan A, Hoogsteden HC, Wijsenbeek MS, Hendriks RW, van den Blink B, Kool M (2018). Increased T-helper 17.1 cells in sarcoidosis mediastinal lymph nodes. Eur Respir J. 51(3).
https://erj.ersjournals.com/content/51/3/1701124
Stadhouders R, Filion GJ, Graf T. (2019). Transcription factors and 3D genome conformation in cell-fate decisions. Nature 569, 345-354.
https://www.nature.com/articles/s41586-019-1182-7
Stadhouders R, Li BWS, de Bruijn MJW, Gomez A, Rao TN, Fehling HJ, van IJcken WFJ, Lim AI, Di Santo JP, Graf T, Hendriks RW (2018). Epigenome analysis links gene regulatory elements in group 2 innate lymphocytes to asthma susceptibility. J Allergy Clin Immunol. 142:1793-1807.
https://www.jacionline.org/article/S0091-6749(18)30295-1/fulltext
Corneth OBJ, Verstappen GMP, Paulissen SMJ, de Bruijn MJW, Rip J, Lukkes M, van Hamburg JP, Lubberts E, Bootsma H, Kroese FGM, Hendriks RW (2017). Enhanced Bruton's Tyrosine Kinase activity in peripheral blood B lymphocytes from patients with autoimmune disease. Arthritis Rheumatol. 69(6):1313-1324.
https://onlinelibrary.wiley.com/doi/full/10.1002/art.40059
Cornelissen R, Hegmans JP, Maat AP, Kaijen-Lambers ME, Bezemer K, Hendriks RW, Hoogsteden HC, Aerts JG (2016). Extended Tumor Control after Dendritic Cell Vaccination with Low-Dose Cyclophosphamide as Adjuvant Treatment in Patients with Malignant Pleural Mesothelioma. Am J Respir Crit Care Med. 193(9):1023-31.
https://www.atsjournals.org/doi/10.1164/rccm.201508-1573OC
Hendriks RW, Yuvaraj S and Kil L (2014). Targeting Bruton’s tyrosine kinase signaling in B cell malignancies. Nature Rev. Cancer 14:219-232.
https://www.nature.com/articles/nrc3702
Collaborations
Internal collaborations
- Department of Cell Biology
- Department of Pediatrics
- Department of Cardiology
- Department of Internal Medicine
- Department of Immunology
External collaborations
- Department of Rheumatology and Clinical Immunology, UMCG Groningen (Prof. F. Kroese)
https://www.rug.nl/staff/departments/10453 - Innate Immunity Unit, Institut Pasteur, Paris, France (Prof. J. di Santo)
https://research.pasteur.fr/en/team/innate-immunity/ - Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain (Prof. T. Graf)
https://www.crg.eu/thomas_graf - Institute of Immunology, Ulm, Germany (Prof. H.J. Fehling; Prof. H. Jumaa)
https://www.uniklinik-ulm.de/immunologie.html - VIB Center for Inflammation Research, Ghent University, Ghent, Belgium (Prof. B.N. Lambrecht; Prof. H. Hammad)
http://www.vib.be/en/research/scientists/Pages/Bart-Lambrecht-Lab.aspx
Funding & Grants
Obtained Grants 2018
Mrace Grant
Unraveling systemic autoimmunity: a critical role for naïve B cells?
Rudi Hendriks
Lung Foundation Consortium Grant
Targeting the origin of the inflammatory cascade in allergic asthma (TORCA)
Rudi Hendriks, Martijn Nawijn (UMCG Groningen), Gerdien Tramper (Franciscus Gasthuis Rotterdam)
PPP Immune System off Balance Consortium
Target to B! Towards patient-tailored immunotherapy to effectively treat B-cell associated disease
Rudi Hendriks, Odilia Corneth (project leader: Taco Kuijpers, AMC Amsterdam)
Erasmus MC Fellowship
Multidimensional epigenomics to understand and target T cell dysfunction in human disease
Ralph Stadhouders
Our team
Head of Laboratory
- Hendriks, Rudi (R.W.)
Group leaders and post-docs
- Corneth, Odilia (O.B.J.)
- Kleinjan, Alex (A.)
- Kool, Mirjam (M.)
- Stadhouders, Ralph (R.)
- Vroman, Heleen (H.)
Research technicians
- Bergen, Ingrid (I.M.)
- Bezemer Koen (K.)
- Hulst van, Jennifer (J.A.C.)
- Hau, Hei Tung (H.T.)
- Jong De – Bruijn de, Marjolein (J.W.)
- Leman, Karolina (K.)
- Lukkes, Melanie (M.)
- Nimwegen van, Menno (M.)
- Özdemir-Göktas, Ilknur (I.)
- Poncin, Myrthe (M.)
- Rafaelian, Areg (A.)
Ph.D. candidates
- Belderbos, Bob (R.A.)
- Das, Tridib (T.)
- Dammeijer, Floris (F.H.W.P.)
- Folkerts, Jelle (J.)
- Goeje de, Pauline (P.L.)
- Gulijk van, Mandy (M.L.)
- Heukels, Peter (P.)
- Koudstaal, Thomas (T.)
- Mankor, Joanne (J.M.)
- Neys, Stefan (S.)
- Schoonhoven van , Anne (A.)
- Van der Ploeg, Esmee (E.K.)
- Rip, Jasper (J.)
- Uden van, Denise (D.)
Collaborative PhD candidates
Boer de, Geertje (G.M.) (Franciscus Gasthuis Rotterdam)
Van Zelst, Cathelijne (C.M.) (Franciscus Gasthuis Rotterdam)
Muggen, Alice (A.F.) (Dept. Immunology, Erasmus MC)
