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Prof. Dr. Aleksandra Wodnar-Filipowicz
Department of Biomedicine,
Basel University Hospital
Hebelstrasse 20
CH-4031 Basel / Switzerland |
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Aleksandra Wodnar-Filipowicz is Professor for Experimental Hematology and group leader at the Department of Biomedicine of the University Hospital in Basel. Her group is interested in mechanisms which regulate the recovery of normal bone marrow function after hematopoietic stem cell (HSC) transplantation. One aim of the studies is to understand the molecular interactions between HSC and their niche. In particular, the group analyzes a role of the hematopoietic cytokine, flt3 ligand, in the regeneration of bone marrow function using mouse models of myelosuppression and HSC transplantation. These studies are now being extended to the regulation in leukemic stem cell (LSC) niches. Using mouse models genetically deficient in niche components, the group studies mechanisms which control the localization and movement of LSC within the bone marrow microenvironment. The second aim of the studies addresses the anti-leukemic potential of natural killer (NK) cells. For this purpose, a transplantation model of human leukemia in immunodeficient NOD/SCID mice has been established. With the focus on the role of the activating NK receptor NKG2D and its ligands in recognition of leukemic targets, the function of histone deacetylase inhibitors in vivo and their synergy with adoptively transfered NK cells in reducing the tumor load is studied. These approaches provide the basis for the ongoing collaborative clinical study with the Stem Cell Transplant Team of the Clinical and Diagnostic Hematology of the University Hospital Basel. This clinical study uses NK cells, activated and expanded ex vivo, as cellular immunotherapy to enhance the graft-versus-leukemia effect and prevent disease relapse after HSC transplantation.
For additional information, see http://biomedizin.unibas.ch/about-us/people/profil/profile/person/wodnar-filipowicz/
Selected original publications
- Chklovskaia E, Nowbakht P, Nissen C, Gratwohl A, Bargetzi M. and Wodnar-Filipowicz A. (2004).Reconstitution of dendritic and natural killer cell subsets after allogeneic stem cell transplantation: Effects of endogenous flt3 ligand. Blood 103:3860-3868.
- Nowbakht P, Ionescu M-C, Rohner A, Kalberer CP, Rossy E, Mori L, Cosman D. De Libero G. and Wodnar-Filipowicz A. (2005). Ligands for natural killer cell-activating receptors are expressed upon the maturation of normal myelomonocytic cells but at low levels in acute myeloid leukemias. Blood 105:3615-3622.
- Siegler U, Kalberer CP, Nowbakht P, S. Meyer-Monard, Tichelli A. and Wodnar-Filipowicz A. (2005). Activated natural killer cells from patients with acute myeloid leukaemia are cytotoxic against autologous leukemic blasts in NOD/SCID mice. Leukemia 19:2215-2222.
- Bridenbaugh S, Kenins L, Bouliong-Pillai E, Kalberer CP, Shklovskaya E, Gratwohl A. and Wodnar-Filipowicz A (2008). Clinical stem cell sources contain CD8+CD3+ T cell receptor-negative cells that facilitate bone marrow repopulation with hematopoietic stem cells Blood112:1735-1738.
- Diermayr S, Himmelreich H, Durovic B, Schneeberger-Mathys A, Siegler U, Langenkamp U, Hofstenge J, Gratwohl A, Tichelli A, Paluszewska M, Wiktor-Jedrzejczak W, Kalberer CP. and Wodnar-Filipowicz A. (2008). NKG2D ligand expression in AML increases in response to HDAC inhibitor valproic acid and contributes to allorecognition by NK cell lines with single KIR-HLA-class I specificities. Blood 111:1428-1436.
- Kenins L, Gill J, Boyd R, Holländer G. and Wodnar-Filipowicz A. (2008). Intra-thymic expression of flt3 ligand enhances thymic recovery post irradiation. J Exp Med 205:523-531.
- Langenkamp U, Siegler U, Jörger S, Diermayr S, Gratwohl A, Kalberer CP. and Wodnar-Filipowicz A. (2009). Human acute myeloid leukemia CD34+CD38- stem cells are susceptible to immunorecognition and lysis by single KIR-expressing natural killer cells. Haematologica in press.
Reviews
- Wodnar-Filipowicz A. (2003). Flt3 Ligand: Role in Control of Hematopoietic and Immune Functions of the Bone Marrow. News in Physiol Sci. 18:247-251.
- Wodnar-Filipowicz A. Biological properties of haemopoietic stem cells.(2008). ESH-EBMT Handbook: Haemopoietic stem cell transplantation. pg 34-43
- Gratwohl A. and Wodnar-Filipowicz A. (2008). A freeway to stem cells? Blood 112:923-4.
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