Activity: Participating in or organising an event types › Participation in workshop, seminar, course
"(Epi)genetic regulation of hemoglobin switching”
Professor Sjaak Philipsen, PhD
Molecular control of erythropoiesis
Erasmus MC, Rotterdam
Prof Sjaak Philipsen’s research is focused on the molecular control of development and terminal differentiation of erythroid cells. In particular, his laboratory has studied epigenetic and transcriptional mechanisms underlying this process. They have combined genomics, proteomics and bioinformatics approaches to dissect erythropoiesis at the molecular, cellular and organismal level. Understanding how the fetal γ-globin genes are silenced in adult erythropoiesis is an important goal, since reactivation of γ-globin expression in adults would ameliorate the symptoms of β-thalassemia and sickle cell anemia, the most common devastating hereditary conditions in the human population with ~300,000 badly affected children born annually. They recently discovered that the KLF1 transcription factor is a major mediator of γ-globin silencing.
His lab is currently studying mice with conditional knockout alleles for Sp-XKLF transcription factors, and using hematopoietic lineage-specific knockouts to dissect their roles in hematopoiesis in general, and erythropoieis and globin regulation in particular.
Perkins, A., Xu, X., Higgs, D.R., Patrinos, G.P., Arnaud, L., Bieker, J.J., Philipsen, S. (2016) Kruppeling erythropoiesis: an unexpected broad spectrum of human red blood cell disorders due to KLF1 variants. Blood, 127, 1856-1862.
Borg, J., Papadopoulos, P., Georgitsi, M., Gutierrez, L., Grech, G., Fanis, P., Phylactides, M., Verkerk, A.J., van der Spek, P.J., Scerri, C.A., Cassar, W., Galdies, R., van Ijcken, W., Ozgur, Z., Gillemans, N., Hou, J., Bugeja, M., Grosveld, F.G., von Lindern, M., Felice, A.E., Patrinos, G.P. and Philipsen, S. (2010) Haploinsufficiency for the erythroid transcription factor KLF1 causes hereditary persistence of fetal hemoglobin. Nat Genet, 42, 801-805.
van Dijk, T.B., Gillemans, N., Pourfarzad, F., van Lom, K., von Lindern, M., Grosveld, F. and Philipsen, S. (2010) Fetal globin expression is regulated by Friend of Prmt1. Blood, 116, 4349-4352.
Whyatt, D., Lindeboom, F., Karis, A., Ferreira, R., Milot, E., Hendriks, R., de Bruijn, M., Langeveld, A., Gribnau, J., Grosveld, F. and Philipsen, S. (2000) An intrinsic but cell-nonautonomous defect in GATA-1-overexpressing mouse erythroid cells. Nature, 406, 519-524.
Marin, M., Karis, A., Visser, P., Grosveld, F. and Philipsen, S. (1997) Transcription factor Sp1 is essential for early embryonic development but dispensable for cell growth and differentiation. Cell, 89, 619-628.