The objective of our HSC research is to understand the wiring of signal transduction pathways in the hematopoietic stem cells (HSC) with the aim of optimizing ex vivo culture and viral transduction. To achieve this, we are studying the effects of Wnt and Notch signals in HSC and the interaction of HSC with the bone marrow niche. To do so, we use genetical models that modulate the Wnt (Conditional Apc knockouts) and Notch pathways(conditional RbpjK knockouts and viral expression of NotchICD), retroviral transductions and cell sorting of purified HSC of human and mouse origin. We subsequently look at the effects of these modulations on gene expression, survival and function of HSC.
Techniques used include:
- Genetic or conditional knockout mouse models (Apc, Wnt3a, RbpjK)
- Retro- or lentiviral expression of transgenes
- Cell sorting by FACS
- mRNA expression measurements (qPCR, microarray, RNASeq)
- Lentiviral DNA barcoding
Relevant publications:
Martijn Brugman, Anna-Sophia Wiekmeijer, Marja van Eggermond, Ingrid Wolvers-Tettero, Anton W Langerak, Edwin de Haas, Leonid V. Bystrykh, Jon J van Rood, Gerald de Haan, Willem E. Fibbe, Frank J.T. Staal.
PNAS, accepted for publication
PMID: Pending
Luis TC, Ichii M, Brugman MH, Kincade P, Staal FJ.
Leukemia. 2012 Mar;26(3):414-21. doi: 10.1038/leu.2011.387. Epub 2011 Dec 15.
PMID: 22173215
Luis TC, Naber BA, Roozen PP, Brugman MH, de Haas EF, Ghazvini M, Fibbe WE, van Dongen JJ, Fodde R, Staal FJ.
Cell Stem Cell. 2011 Oct 4;9(4):345-56. doi: 10.1016/j.stem.2011.07.017.
PMID: 21982234
Maetzig T, Brugman MH, Bartels S, Heinz N, Kustikova OS, Modlich U, Li Z, Galla M, Schiedlmeier B, Schambach A, Baum C. Blood. 2011 Mar 17;117(11):3053-64. Epub 2011 Jan 19.
PMID: 21248062