My research focuses on the molecular biology of the developmental and functional program of lymphocytes. The aims comprise characterization of signal transduction pathways, lymphoid-specific transcription factors and epigenetic regulation that implement cellular survival, differentiation and proliferation at specific checkpoints. A main line of research is the identification of the function of Bruton’s tyrosine kinase (Btk), which is involved in various signalling pathways in B cells, including the B cell antigen receptor. We particularly study aberrant Btk activation and effects of BTK inhibition in mature B cells in systemic autoimmune disease, interstitial lung disease and leukemia in human and animal models.
Department of Pulmonary Medicine, Erasmus MC Rotterdam, The Netherlands
Singh SP, Pillai SY, de Bruijn MJW, Stadhouders R, Corneth OBJ, van den Ham HJ, Muggen A, van IW, Slinger E, Kuil A, et al. Cell lines generated from a chronic lymphocytic leukemia mouse model exhibit constitutive Btk and Akt signaling. Oncotarget. 2017.
Corneth OBJ, Verstappen GMP, Paulissen SMJ, de Bruijn MJW, Rip J, Lukkes M, van Hamburg JP, Lubberts E, Bootsma H, Kroese FGM, et al. Enhanced Bruton’s Tyrosine Kinase Activity in Peripheral Blood B Lymphocytes From Patients With Autoimmune Disease. Arthritis Rheumatol. 2017.
Hendriks RW, Yuvaraj S, Kil LP. Targeting Bruton’s tyrosine kinase in B cell malignancies. Nat Rev Cancer. 2014.
Kil LP, de Bruijn MJ, van Nimwegen M, Corneth OB, van Hamburg JP, Dingjan GM, Thaiss F, Rimmelzwaan GF, Elewaut D, Delsing D, et al. Btk levels set the threshold for B-cell activation and negative selection of autoreactive B cells in mice. Blood. 2012.
Ribeiro de Almeida C, Stadhouders R, de Bruijn MJ, Bergen IM, Thongjuea S, Lenhard B, van Ijcken W, Grosveld F, Galjart N, Soler E, et al. The DNA-binding protein CTCF limits proximal Vkappa recombination and restricts kappa enhancer interactions to the immunoglobulin kappa light chain locus. Immunity. 2011.
Claudia Ribeiro de Almeida: CTCF: A Crucial Regulator of Gene Expression in Lymphocytes. Awarded: 2010
Van Ta: Role of Pre-B Cell Receptor Signaling Molecules in B Cell Differentiation and Tumor Suppression. Awarded: 2010
Laurens Kil: Btk in Autoimmunity and leukemia: too much of a good thing? Awarded: 2013
Current PhD projects
Jasper Rip: BTK signaling in systemic autoimmunity and B cell malignancies
Simar Pal Singh: B cell receptor signaling in chronic lymphocytic leukemia