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Medizinische Klinik III
Hematopoietic stem cell research
Our team is focused on investigation of the regulation of hematopoietic stem cells. We use the murine hematopoietic system to analyze the role of different molecules in regulation of cell cycle control, apoptosis, self renewal and differentiation of different subsets of primitive bone marrow cells. One of physiological features of stem cells is their rareness, and yet this often limits their clinical application. Using mutant mice we have demonstrated that changes in stem cell proliferation activity by affecting the expression of the cell cycle regulator p16INK4A has an impact on the the regeneration ability of aged hematopoietic stem cells and increases their number (Janzen et al, 2006). Enhanced Proliferation of hematopoietic stem cells was also observed in another mutant mouse model: Caspase-3 deficient mice also exhibit an increased stem cell pool by enhanced proliferation rather than by affecting the rate of apoptosis (Janzen et al, 2008). Another emphasis of our research is the ambition to understand how the microenvironment is influencing the fate of hematopoietic stem cells. Affecting signaling from the bone marrow niche cells to the hematopoietic stem cells by intrinsic or extrinsic signaling modifications were demonstrated to affect stem cell behaviour (Janzen et al, 2008; Fleming et al, 2008). Also changes in the achitecture of bone marrow can cause transformation towards myeloproliferative diseases (Larsson et al, 2008).
The goal of our research is to contribute to the general understanding of stem cell regulation and development of diseases. On the long term we try to improve the treatment of malignant diseases through understanding of the stem cell biology.
Ausgewählte Publikationen seit 2005
- Janzen V, Fleming HE, Riedt T, Karlsson G, Riese MJ, Lo Celso , Reynolds G, Milne CD, Paige CJ, Karlsson S, Woo M, Scadden DT. Cell Stem Cell. 2008 Jun 5;2(6):584-94.
- Larsson J, Ohishi M, Garrison B, Aspling M, Janzen V, Adams GB, Curto M, McClatchey AI, Schipani E, and Scadden DT. Nf2/merlin regulates hematopoietic stem cell behavior by altering microenvironmental architecture. Cell Stem Cell, 2008 Aug 7;3(2):221-7.
- Orford K, Lai W, Dao MC, Worhunsky D, Janzen V, Park PJ, Scadden DT. Genome-wide Distribution of a Euchromatic Histone Modifications Defines Hematopoietic Differentiation Potential. Dev Cell. 2008 May;14(5):798-809.
- Fleming HE, Janzen V, Lo Celso C, Guo J, Leahy KM, Kronenberg HM and Scadden DT. Wnt signaling in the niche enforces hematopoietic stem cell quiescence and is necessary to preserve self-renewal in vivo. Cell Stem Cell. 2008 Mar 6;2(3):274-83
- Chen T, Shao Y, Arzigian M, Janzen V, Attar E, Xie Y, Scadden DT, Wang ZZ. Stromal Cell-Derived Factor-1/CXCR4 Signaling Modifies the Capillary-Like Organization of Human Embryonic Stem Cell-Derived Endothelium In Vitro. Stem Cells. 2007 Feb;25(2):392-401.
- Janzen V, Forkert R, Fleming HE, Saito Y, Waring MT, Dombkowski DM, Cheng T, DePinho RA, Sharpless NE, Scadden DT. Stem cell aging modified by the cyclin dependent kinase inhibitor, p16INK4a. Nature 2006 Sep 28;443(7110):421-6.
- Janzen V and Scadden DT. Stem cells: good, bad and reformable. Nature. 2006 May 25;441(7092):418-9.
- Wernig G*, Janzen V*, Schafer R, Zweyer M, Knauf U, Hoegemeier O, Mundegar RR, Garbe S, Stier S, Franz T, Wernig M, Wernig A. The vast majority of bone-marrow-derived cells integrated into mdx muscle fibers are silent despite long-term engraftment. Proc Natl Acad Sci 2005 102(33):11852-7. *Contributed equally.
- Okuducu AF, Janzen V, Ko Y, Hahne JC, Lu H, Ma ZL, Albers P, Sahin A, Wellmann A, Scheinert P, Wernert N. Cellular retinoic acid-binding protein 2 (CRABP2) is down-regulated in prostate cancer. Int J Oncol. 2005 Nov;27(5):1273-82.
- Rodrigues NP, Janzen V, Forkert R, Dombkowski DM, Boyd AS, Orkin SH, Enver T, Vyas P and Scadden DT. Haploinsufficiency of GATA-2 perturbs adult hematopoietic stem cell homeostasis. Blood, 2005 Jul 15;106:477-84.