Mariusz Z. Ratajczak MD, PhD, DSci, dhc

Education:

M.D. - Magna Cum Laude, Medicine, Pomeranian Medical University, Szczecin, Poland; 1981
Ph.D., Medicine, Center for Clinical & Experimental Medicine of Polish Academy of Sciences, Warsaw, Poland; 1986
D.Sci. (Habilitated Ph.D.), Medicine, Center for Clinical & Experimental Medicine of Polish Academy of Sciences, Warsaw, Poland; 1989

Curriculum Vitae

Current Positions:

Profesor, Division of Hematology/Oncology, Department of Medicine, University of Louisville, Louisville, KY USA
Director - Stem Cell Institute, Division of Hematology/Oncology, James Graham Brown Cancer Center, University of Louisville
Member, Immuno-Oncology Program, James Graham Brown Cancer Center, University of Louisville
Visiting Professor, Department of Regenerative Medicine, Warsaw Medical University, Warsaw, Poland; 2015-
Visiting Professor, Kansai University, Osaka, Japan; 2007-
Visiting Professor, Fudan University, Shanghaj, PRC; 2008-

Contact Information:

Mariusz Z. Ratajczak MD, PhD, D.Sci, d.hc
Professor and Endowed Chair
Stem Cell Institute at James Graham Brown Cancer Center
University of Louisville, 500 S. Floyd Street, Rm. 107
Louisville, KY 40202, USA
Tel: (502) 852-1788, Fax: (502) 852-3032,

Email:

Research Description:

Dr. Ratajczak is an internationally known specialist in the field of adult stem cell biology.  His 2005 discovery of embryonic-like stem cells in adult bone marrow tissues has the potential to revolutionize the field of regenerative medicine. This discovery may lead to new treatments for cancer, heart disease, eye disease, diabetes and neurodegenerative disorders. Dr. Ratajczak is also known from his work on novel mechanisms of mobilization and homing of stem cells, biological role of extracellular microvesicles and molecular mechanisms of cancer metastasis.

1. The role of developmentally early stem cells isolated from the adult tissues in regeneration. Identification of new mechanisms responsible for tissue/organ regeneration. Dr. Ratajczak developed a concept of circulating small pluripotent very small embryonic-like stem cells (VSELs) and is developing new strategies to isolate those cells from bone marrow, mobilized peripheral blood, cord blood and peripheral tissues.

2. The role of complement in stem cell homing/mobilization. Another area of investigations in Dr. Ratajczak’s laboratory is to elucidate the role of complement proteins in regulating human hematopoiesis. Dr. Ratajczak’s group identified a novel role of C3 complement cleavage fragments modulate the SDF-1-CXCR4 axis and thus play an important role in retaining human CXCR4+ hematopoietic stem cells in the bone marrow. Dr. Ratajczak also observed that antagonists of C3a receptor enhance G-CSF-mediated mobilization of hematopoietic stem cells into peripheral blood. This strategy could be explored in vivo as a new strategy to mobilize the so called “poor mobilizers”.

3. The role of bioactive lipids in stem cell homing/mobilization and cancer metastasis. Dr. Ratajczak’s laboratory is to elucidate the role of sphingosine-1 phosphate and ceramid-1 phosphate in regulating normal human hematopoiesis and directing mobilization and homing of various BM-derived adult stem cells. His group pioneered this field. In parallel his group is studying effect of bioactive lipids in cancer metastasis.

4. Biological effects of microvesciles and exosomes. Dr. Ratajczak’s laboratory is studying the role of membrane derived microparticles shed from the eukaryotic cells and their role in various biological processes. Recently, microvesicles, isolated from embryonic stem cells, were used by his group to improve ex vivo expansion and survival of hematopoietic stem/progenitor cells. He is also interested in the role of microvesicles in the progression of cancer. He found that platelet derived microvesicles may regulate metastatic behavior of cancer cells and for a first time described that they play a novel role in horizontal transfer mRNA and miRNA between the cells.

Literature Cited:

  1. Ratajczak M.Z., Luger S.M.,  DeRiel K., Abraham J., Calabretta B., Gewirtz A.M.: Role of the KIT protoncogene in normal and malignant  human hematopoiesis.  Proc. Natl. Acad. Sci. USA, 1992, 89, 1710 - 1714.  PMID: 1371882
  2. Majka M, Rozmyslowicz T, Lee B, Pietrzkowski Z, Gaulton GN, Silberstein L, Ratajczak MZ.: Bone Marrow CD34+ cells and megakaryoblasts secrete beta-chemokines; implications for infectability by M-tropic human immunodeficiency virus (R5 HIV). J. Clin. Invest. 1999, 104, 1739-1749.  PMID: 10606628
  3. Majka M, Janowska-Wieczorek A, Ratajczak J, Ehrenman K, M.A. Kowalska, Gewirtz AM, Emerson SG, Ratajczak MZ. Numerous growth factors, cytokines and chemokines are secreted by human CD34+ cells, myeloblasts, erythroblasts and megakaryoblasts and regulate normal hematopoiesis in an autocrine/paracrine manner. Blood 2001, 97, 3075-3085.  PMID: 11342433
  4. Libura J, Drukala J, Majka M, Tomeascu O, Navenot JM, Kucia M, Marquez L, Peiper SC, Barr FG, Janowska-Wieczorek A, Ratajczak MZ.: CXCR4-SDF-1 signaling is active in rhabdomyosarcoma cells and regulates locomotion, chemotaxis and adhesion. Blood 2002,100, 2597-2606.  PMID: 12239174
  5. Reca R, Mastellos D, Majka M, Marquez L, Ratajczak J, Franchini S, Glodek A, Honczarenko M, Spruce LA, Janowska-Wieczorek A, Lambris JD, Ratajczak MZ.: Functional receptor for C3a anaphylatoxin is expressed by normal hematopoietic stem/progenitor cells and C3a enhances homing-related responses of early hematopoietic cells to SDF-1. Blood 2003, 101, 3784-3793.  PMID: 12511407
  6. Wysoczynski M, Reca R, Ratajczak J, Kucia M, Shirvaikar N, Mills M, Wanzeck J, Honczarenko M, Janowska-Wieczorek A, Ratajczak M.Z. Incorporation of CXCR4 into Membrane Lipid Rafts Primes Homing-related responses of Hematopoietic Stem Cells to an SDF-1 Gradient. Blood 2005, 105, 40-48.  PMID: 15328152
  7. Kucia M, Reca R, Campbell FR, 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, 20:857-869.  PMID: 16498386
  8. Ratajczak MZ, LeeHK, WysoczynskiM, WanW, MarliczW, LaughlinMJ, KuciaM, Janowska-WieczorekA, RatajczakJ. Novel insight into stem cell mobilization - Plasma Sphigosine 1 – phosphate is a major chemoattractant that directs egress of hematopoietic stem progenitor cells from bone marrow and its level in peripheral blood increases during mobilization due to activation of complement cascade/membrane attack complex.  Leukemia 2010, 24, 976-985.  PMID: 20357827
  9. Ratajczak MZ, Kucia M, Jadczyk T, Greco NJ, Wojakowski W, Tendrea M, Ratajczak J. Pivotal Role of Paracrine Effects in Stem Cell Therapies in Regenerative Medicine - Can We Translate Stem Cell-Secreted Paracrine Factors and Microvesicles into Better Therapeutic Strategies? Leukemia 2012 Jun; 26(6):1166-73.  PMID: 22182853+
  10. Ratajczak MZ, Kucia M, Jadczyk T, Greco NJ, Wojakowski W, Tendrea M, Ratajczak J. Pivotal Role of Paracrine Effects in Stem Cell Therapies in Regenerative Medicine - Can We Translate Stem Cell-Secreted Paracrine Factors and Microvesicles into Better Therapeutic Strategies? Leukemia 2012 Jun; 26(6):1166-73.  PMID: 22182853
  11. 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 2013 Apr; 35(2):315-30.  PMID: 22218782
  12. RatajczakMZ, Shin DM, SchneiderG, 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, 773–779.  PMID: 23135355
  13. SchneiderG, BryndzaE, Abdel-LatifA, RatajczakJ, MajM, TarnowskiM, KlyachkinY, HoughtonP, MorrisAJ, VaterA, KlussmannS, KuciaM, RatajczakMZ. Bioactive lipids sphingosine-1-phosphate and ceramide-1- phosphate are pro-metastatic factors in human rhabdomyosarcomas cell lines, and their tissue level increases in response to radio/chemotherapy. Mol. Cancer Res. 2013, 11, 793-807.
  14. Borkowska S, Suszynska M, Mierzejewska K, Ismail A, Budkowska M, Salata D, Dolegowska B, Kucia M,Ratajczak J, Ratajczak MZ. Novel evidence that crosstalk between the complement, coagulation, and fibrinolysis proteolytic cascades is involved in mobilization of hematopoietic stem/progenitor cells (HSPCs). Leukemia 2014, 28, 2148–2154.  PMID: 24667943
  15. SchneiderG, Sellers ZP, Abdel-LatifA, MorrisAJ, RatajczakMZ. Bioactive Lipids, LPC and LPA, are Novel Pro-metastatic Factors and Their Tissue Levels Increase in Response to Radio/Chemotherapy. Mol Cancer Res 2014, 12, 1560–1573. PMID: 25033840

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