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Prof. Dr. Aleksandra Wodnar-Filipowicz
Co-ordinator
Basel Stem Cell Center of Competence
Medical Faculty
University of Basel
Klingelbergstrasse 61
CH-4056 Basel
Switzerland |
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Aleksandra Wodnar-Filipowicz is Professor for Experimental Hematology. She acts as Co-ordinator of the Basel Stem Cell Network (BSCN) at the University of Basel. Her research interests focus on understanding the interactions of normal and cancer stem cells in the bone marrow microenvironment. One aim is to study mechanisms which regulate the recovery of normal bone marrow function after hematopoietic stem cell (HSC) transplantation. In particular, she is interested in a role of the hematopoietic cytokine, flt3 ligand, in the regeneration of bone marrow function after myelosuppression and HSC transplantation. Using mouse models genetically deficient in niche components, the group studies mechanisms which control the leukemic stem cells within the bone marrow microenvironment. These studies are now being extended to the analysis of bone marrow involvement in metastases of mammary carcinoma (collaboration with Nancy Hynes at the Friedrich Miescher Institute of BIomedical Research in Basel). The second aim of the studies addresses the anti-leukemic potential of natural killer (NK) cells. A transplantation model of human leukemia in immunodeficient NOD/SCID mice has been established to perform adoptive transfer of NK cells and to study the cooperative effect of histone deacetylase inhibitors on reducing the tumor load in vivo. 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.
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. Haematologica94:1590-1594.
- Kenins L, Gill JW, Holländer GA. and Wodnar-Filipowicz A. (2010). Flt3 ligand-receptor interaction is important for maintenance of early thymic progenitor numbers in steady-state thymopoiesis. Eur J Immunol. 40:81-90.
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 112:923-924.
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