Magdalena Kucia, Ph.D., DSci

Education:

2000 M.S. Jagiellonian University, Cracow, Poland, Molecular Biology - summa cum laude
2004 Ph.D. Faculty of Biotechnology, Jagiellonian University, Cracow, Poland, Biochemistry - based on the dissertation “New insight on the pool of bone marrow stem cells” - summa cum laude
2014 D.Sc. Pomeranian Medical University, Szczecin, Poland – “Identification and molecular characterization of pluripotent VSELs residing in murine bone marrow”

Curriculum Vitae

Current Positions:

Assistant Professor, Stem Cell Institute, James Graham Brown Cancer Center, University of Louisville, KY
Member, James Graham Brown Cancer Center

Contact Information:

Developmental Biology Program
500 South Floyd Street, Room 102
University of Louisville
Stem Cell Institute
James Graham Brown Cancer Center
Louisville, KY 40202
Phone: 502.852.3722

E-mail: mjkuci01@louisville.edu

 

Research Description:

In 2006 I was appointed to the faculty of the Department of Medicine at University of Louisville. I was a member of the team that described very small embryonic like stem cells. I have published numerous book chapters and more than 130 peer reviewed Pub-Med listed papers. I am a member of editorial board of Journal of Cancer Stem Cell Research and reviewer for Leukemia, Stem Cells and Experimental Hematology.

Her scientific research is focused on:

 

    I. Identification of murine and human VSELs, developmental origin and molecular characterization of these cells and role of imprinted genes in maintaining their quiescent state. Imprinted genes have a crucial role in fetal growth, development, pluripotency of stem cell and tumorigenesis. Potential modulation of mechanisms that control expression of imprinted genes in VSELs would be crucial for developing powerful strategies to expand these cells in order to employ them efficiently in the clinic.

      II. The role of insulin and insulin growth factors signaling in stem cells aging.

        The increase in caloric intake and elevated insulin and/or insulin-like growth factor (Ins/IGF) level in peripheral blood has negative impact on life span. In contrary, caloric restriction (CR) and decrease in insulin/insulin like growth factor signaling (IIS) increase lifespan in worms, flies, and mammals. Consistent with this general observation, mice with low circulating insulin-like growth factor-1 (IGF-1) levels (e.g., Laron – GHR-/-, Ames, and Snell dwarfs) live much longer than their normal littermates. By contrast, mice with high levels of circulating IGF-1 (e.g., transgenic mice that overexpressed bovine growth hormone –bGH) have significantly reduced life span. Moreover, mice with attenuated expression of RasGrf1, a small GTP exchange factor (GEF) for Ras, also live longer. This latter finding can be explained by the involvement of RasGrf1 in signaling through insulin and insulin-like growth factor-1 receptors (InsR and IGF-1R, respectively).

        Our data indicate a detrimental effect of elevated IIS on the number of VSELs and HSCs in adult murine BM. We propose a novel paradigm for aging in which epiblast-derived VSELs, which are deposited in adult tissues as most primitive population of stem cells involved in tissue/organ rejuvenation, are depleted with time in IIS-dependent manner. Furthermore, since Igf2-H19 and RasGrf1 genes are paternally imprinted genes and thus expressed from paternal chromosomes, the data demonstrate indirectly that some paternally imprinted genes play a crucial role in the control of longevity.

          III. The role of chemokines/cytokines in metastasis of rhabdomyosarcoma. We explore a concept that SDF-1-CXCR4 axis is the master regulator of trafficking of both normal and cancer stem cells and postulates that the metastasis of cancer stem cells and migration of normal stem cells are mirror images and involve similar mechanism. In consequences, strategies aimed at modulating the SDF-1-CXCR4 axis could have important clinical application both in regenerative medicine and oncology.

            IV. The role of pituitary gonadotropins in human malignant hematopoiesis. It has been postulated that hematopoietic stem/progenitor cells (HSPCs) can become specified from a population of migrating primordial germ cells (PGCs) isolated from embryos. In support of this intriguing possibility, HSPCs and PGCs are both highly migratory populations of stem cells, and evidence accumulated on sharing of several genes (e.g., Sall4) as well as chromosomal aberrations between germline tumors and leukemias or lymphomas, which suggests their common clonal origin. In fact we noticed recently that normal murine HSPCs express several functional receptors for pituitary gonadal hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) in addition to gonadal hormones including estrogens, androgen and progesterone. Our data demonstrated for the first time that pituitary-secreted gonadotrophins stimulate migration, adhesion and proliferation of leukemic cells. This effect seems to be direct, as the receptors for these hormones respond to stimulation by phosphorylation of intracellular pathways involved in cell proliferation. Human myeloid established leukemia cell lines and primary patients blasts also responded to stimulation by gonadal sex hormones.

              Literature Cited:

              1. Shin DM, Zuba-Surma EK, Wu W, Ratajczak J, Wysoczynski M, Ratajczak MZ, Kucia M. Novel epigenetic mechanisms that control pluripotency and quiescence of adult bone marrow-derived Oct4(+) very small embryonic-like stem cells. Leukemia 2009; 23(11): 2042-51. doi: 10.1038/leu.2009.153.
              2. Kucia M, Reca R, Campbell FR, Zuba-Surma E, Majka M, Ratajczak J, Ratajczak MZ. A population of very small embryonic-like (VSEL) CXCR4(+)SSEA-1(+)Oct-4+ stem cells identified in adult bone marrow. Leukemia 2006; 20(5):857-69.
              3. Ratajczak MZ, Shin DM, Schneider G, Ratajczak J, Kucia M. Parental imprinting regulates insulin-like growth factor signaling: a Rosetta Stone for understanding the biology of pluripotent stem cells, aging and cancerogenesis. Leukemia 2013; 27(4):773-9. doi: 10.1038/leu.2012.322.
              4. Tarnowski M, Schneider G, Amann G, Clark G, Houghton P, Barr FG, Kenner L, Ratajczak MZ, Kucia M. RasGRF1 regulates proliferation and metastatic behavior of human alveolar rhabdomyosarcomas. Int J Oncol 2012; 41(3):995-1004. doi: 10.3892/ijo.2012.1536.
              5. Kucia M, Masternak M, Liu R, Shin DM, Ratajczak J, Mierzejewska K, Spong A, Kopchick JJ, Bartke A, Ratajczak MZ. The negative effect of prolonged somatotrophic/insulin signaling on an adult bone marrow-residing population of pluripotent very small embryonic-like stem cells (VSELs). Age (Dordr) 2013; 35(2):315-30. doi: 10.1007/s11357-011-9364-8.
              6. Shin DM, Liu R, Wu W, Waigel SJ, Zacharias W, Ratajczak MZ, Kucia M. Global gene expression analysis of very small embryonic-like stem cells reveals that the Ezh2-dependent bivalent domain mechanism contributes to their pluripotent state. Stem Cells Dev 2012; 21(10):1639-52. doi: 10.1089/scd.2011.0389.
              7. Kucia M, Shin DM, Liu R, Ratajczak J, Bryndza E, Masternak MM, Bartke A, Ratajczak MZ. Reduced number of VSELs in the bone marrow of growth hormone transgenic mice indicates that chronically elevated Igf1 level accelerates age-dependent exhaustion of pluripotent stem cell pool: a novel view on aging. Leukemia 2011; 25(8):1370-4. doi: 10.1038/leu.2011.98.
              8. Tarnowski M, Grymula K, Liu R, Tarnowska J, Drukala J, Ratajczak J, Mitchell RA, Ratajczak MZ, Kucia M. Macrophage migration inhibitory factor is secreted by rhabdomyosarcoma cells, modulates tumor metastasis by binding to CXCR4 and CXCR7 receptors and inhibits recruitment of cancer-associated fibroblasts. Mol Cancer Res 2010; 8(10):1328-43. doi: 10.1158/1541-7786.MCR-10-0288.
              9. Ratajczak MZ, Shin DM, Kucia M. Very small embryonic/epiblast-like stem cells: a missing link to support the germ line hypothesis of cancer development? Am J Pathol 2009; 174(6):1985-92. doi: 10.2353/ajpath.2009.081143.
              10. Ratajczak MZ, Jadczyk T, Schneider G, Kakar SS, Kucia M. Induction of a tumor-metastasis-receptive microenvironment as an unwanted and underestimated side effect of treatment by chemotherapy or radiotherapy. J Ovarian Res 2013; 6(1):95. doi: 10.1186/1757-2215-6-95.
              11. Schneider G, Bryndza E, Abdel-Latif A, Ratajczak J, Maj M, Tarnowski M, Klyachkin YM, Houghton P, Morris AJ, Vater A, Klussmann S, Kucia M, Ratajczak MZ. Bioactive lipids S1P and C1P are prometastatic factors in human rhabdomyosarcoma, and their tissue levels increase in response to radio/chemotherapy. Mol Cancer Res 2013; 11(7):793-807. doi: 10.1158/1541-7786.MCR-12-0600.
              12. Kucia M, Halasa M, Wysoczynski M, Baskiewicz-Masiuk M, Moldenhawer S, Zuba-Surma E, Czajka R, Wojakowski W, Machalinski B, Ratajczak MZ. Morphological and molecular characterization of novel population of CXCR4+ SSEA-4+ Oct-4+ very small embryonic-like cells purified from human cord blood: preliminary report. Leukemia 2007; 21(2):297-303.
              13. Ratajczak J, Kucia M, Mierzejewska K, Liu R, Kim CH, Natarajan N, Sharma V, Miller DM, Maciejewski J, Ratajczak MZ.  A novel view of paroxysmal nocturnal hemoglobinuria pathogenesis: more motile PNH hematopoietic stem/progenitor cells displace normal HSPCs from their niches in bone marrow due to defective adhesion, enhanced migration and mobilization in response to erythrocyte-released sphingosine-1 phosphate gradient. Leukemia 2012; 26(7):1722-5. doi: 10.1038/leu.2012.46.
              14. Kucia M, Wysoczynski M, Wu W, Zuba-Surma EK, Ratajczak J, Ratajczak MZ. Evidence that very small embryonic-like stem cells are mobilized into peripheral blood. Stem Cells 2008;  26(8):2083-92. doi: 10.1634/stemcells.2007-0922.
              15. Ratajczak MZ, Machalinski B, Wojakowski W, Ratajczak J, Kucia M. A hypothesis for an embryonic origin of pluripotent Oct-4(+) stem cells in adult bone marrow and other tissues. Leukemia 2007; 21(5):860-7.

              PubMed Information