Anna Janowska-Wieczorek,
- Stem Cell Biology
- Stem Cell Mobilization, Collection & Transplantation
- Novel Cellular Therapies
Developmental research - About two decades ago, we developed in Edmonton a hematopoietic stem cell transplantation program and established the CBS Stem Cell Laboratory for the collection/processing of peripheral blood stem cells for their use in autologous stem cell transplantation in cancer patients. Our CBS team was among the first to provide this service in Canada. Currently, my clinical stem cell transplantation programs include the development of new methods i) to improve mobilization of HSPC in order to reduce the number and volume of leukaphereses, and (ii) to improve HSPC homing to speed up hematopoietic engraftment and reduce the need for blood products in the post-transplant period.
Basic research - The main focus of my laboratory has been stem cell transplantation and development of novel cellular therapies. We have been working on ex vivo expansion of megakaryocytic progenitor cells and mesenchymal stem cells (MSC) obtained from cord blood and bone marrow for their future use in transplantation. In order to elucidate the basic mechanisms of hematopoietic stem cell mobilization and homing we were investigating the interactions of the stromal-derived factor (SDF)-1-CXCR4 axis, HGF-c-met axis, matrix metalloproteinases (MMP-2, MMP-9, MT1-MMP), platelet-derived microparticles and complement system (C3a, C5a) in these processes. We recently discovered the critical role that MT1-MMP and C5a play in mobilization of HSPC.
My research has been funded by CIHR, CBS/CIHR (Blood Utilization & Conservation Initiative), NSERC/CIHR, CBS R & D Intramural Program and NIH (US).
Selected Publications:
Janowska-Wieczorek A, Wysoczynski M, Kijowski J, Marquez-Curtis L, Machalinski B, Ratajczak J, Ratajczak MZ. Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. Int J Cancer 113:752-760, 2005.
Wysoczynski M, Reca R, Ratajczak J, Kucia M, Shirvaikar N, Honczarenko M, Wanzeck J, Janowska-Wieczorek A, Ratajczak MZ. Incorporation of CXCR4 into membrane lipid rafts primes homing-related responses of hematopoietic stem/progenitor cells to an SDF-1 gradient. Blood 105:40-48, 2005.
Kucia M, Reca R, Miekus K, Wanzeck J, Wojakowski W, Janowska-Wieczorek A, Ratajczak J, Ratajczak MZ. Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1-CXCR4 axis. Stem Cells 23:879-894, 2005.
Son B-R, Marquez-Curtis LA, Kucia M, Ratajczak MZ, Janowska-Wieczorek A. Migration of bone marrow and cord blood mesenchymal stem cells is regulated by SDF-1-CXCR4 and HGF-c-met axes and involves matrix metalloproteinases. Stem Cells 24:1254-1264, 2006.
Janowska-Wieczorek A, Marquez-Curtis L, Wysoczynski M, Ratajczak MZ. Enhancing effect of platelet-derived microvesicles on the invasive potential of breast cancer cells. Transfusion 46:1199-1209, 2006.
Shirvaikar N, Reca R, Marquez-Curtis L, Lee SF, Ratajczak MZ, Janowska-Wieczorek A. CFU-Meg progenitors ex vivo expanded from cord blood maintain their in vitro homing potential and express matrix metalloproteinases. Cytotherapy 10 (2):182-192; 2008.
Marquez-Curtis LA, Jalili A, Deiteren K, Shirvaikar N, Lambeir A-M, Janowska-Wieczorek A. Carboxypeptidase M is expressed by human bone marrow cells and cleaves the C-terminal lysine of SDF-1a: its possible role in mobilization. Stem Cells 26 (5):1211-1220, 2008
Marquez-Curtis LA, Turner AR, Larratt LM, Letcher B, Lee SF, Janowska-Wieczorek A. CD34+ cell responsiveness to stromal cell-derived factor-1a underlies rapid engraftment after transplantation with peripheral blood stem cells. Transfusion 49 (1):161-169, 2009.
Gul H, Marquez-Curtis L, Jahroudi N, Turner AR, Janowska-Wieczorek A. Valproic acid increases CXCR4 expression in hematopoietic stem/progenitor cells by chromatin remodelling. Stem Cells & Dev 18 (6): 2009.