Mariusz Z. Ratajczak, MD, PhD, DSci


Henry M. & Stella M. Hoenig Endowed Chair in Cancer Research; Professor of Medicine; Leader, Developmental Biology Program, James Graham Brown Cancer Center

Research Program
Developmental Biology

Education
M.D., Pomeranian Medical University, Szczecin, Poland, 1981
Ph.D., Center for Clinical & Experimental Medicine of the Polish Academy of Sciences, Warsaw, Poland, 1986
D.Sc., Center for Clinical & Experimental Medicine of the Polish Academy of Sciences, Warsaw, Poland, 1989

Research and Professional Experience
1981-1984
Research Assistant, Department of Clinical Gastroenterology, Pomeranian Medical University

1984-1986
PhD Program, Polish Academy of Sciences, Warsaw, Poland

1986-1989
Assistant Professor, Center for Clinical & Experimental Medicine, Polish Academy of Sciences, Warsaw

1990-1993
Postdoctoral Fellow, Department of Pathology, University of Pennsylvania, Philadelphia

1989-1994
Associate Professor of Internal Medicine, Center for Clinical & Experimental Medicine, Polish Academy of Sciences, Warsaw

1996-1998
Research Assistant Professor Department of Pathology, University of Pennsylvania, Philadelphia

1998-2000
Research Associate Professor Department of Medicine, University of Pennsylvania, Philadelphia

2000-2001
Research Associate Professor, Department of Pathology & Laboratory Medicine, University of Pennsylvania, Philadelphia

2001-present
Professor of Medicine, University of Louisville, Louisville, KY

2001-present
Senior Scientist and Leader - Developmental Biology Program, James Graham Brown Cancer Center,
University of Louisville

2007-present
Stella M. and Henry M. Hoenig Endowed Chair in Cancer Research at the James Graham Brown Cancer Center, University of Louisville

Selected Awards and Professional Honors
1979               
Award for Young Student Scientists from Polish Academy of Sciences

1980
Copernicus Award from Ministry of Health

1981
M.D. Magna cum Laude - first in class (of 280 students)

1986
Ph.D. thesis with Award

1989
D.Sci.

1997-present
Editorial Board, Stem Cells

1998-present
Associate Editor, Folia Histochemica et Cytobiologica

2001
Honorary Member of Polish Society of Cytobiology and Histochemistry

2002
Chad Kopple Spirit Award from the Leukemia and Lymphoma Society

2004-present  
Editorial Board, Experimental Hematology

2004               
Individual Award from Polish Ministry of Health for Scientific Achievements

2005               
Sniadecki Award from Polish Acadaemy of Sciences

2005-Present
Section Editor, Leukemia

2006-Present
Editor-in-Cheif, Central European Journal of Biology

2006-Present
Member, Editorial Board, Journal of Cellular and Molecular Medicine

2006   
The Annual Award in Medicine and Biology from The Foundation for Polish Science (the highest scientific award in Poland)

2008  
Elected Foreign Member of the Polish Academy of Arts

Research Interest

Dr. Ratajczak obrained his MD from the Pomeranian Medical University in Szczecin, Poland, and his PhD from Polish Academy of Sciences in Warsaw, Poland. Since 1990 he is working as scientist in US. He spend 11 years at University of Pennsylvania in Philadelphia, where he was promoted to a rank of the Associate Professor. Four years ago Dr. Ratajczak joined the James Graham Brown Cancer Center as a Professor in the Department of Medicine and as Head of Stem Cell Biology Program at James Graham Brown Cancer Center.

Current Research Projects

The role of circulating stem cells in regeneration. Dr. Ratajczak is interested in identifying new mechanisms responsible for tissue regeneration. He developed a concept of CXCR4 positive circulating tissue specific stem cells and their competition for common niches in various tissues/organs. He is developing new strategies to isolate those tissue specific stem cells from mobilized peripheral blood and peripheral tissues. Dr. Ratajczak’s group identifies factors that are responsible for trafficking of these cells during tissue injury and stress, and their recruitment to the damaged organs/tissues.

The role of CXCR4-SDF-1 axis in cancer metastasis. The ?-chemokine, stromal derived factor (SDF)-1 and the G-protein-coupled seven-span transmembrane receptor CXCR4 axis regulates the trafficking of various cell types. Dr. Ratajczak’s group explores a concept that the SDF-1–CXCR4 axis is a master regulator of trafficking of both normal and cancer stem cells. Supporting this is growing evidence that SDF-1 plays a pivotal role in the regulation of trafficking of normal hematopoietic stem cells (HSC) and their homing/retention in bone marrow. Moreover, functional CXCR4 is also expressed on non-hematopoietic tissue-committed stem/progenitor cells (TCSC), hence the SDF-1–CXCR4 axis emerges as a pivotal regulator of trafficking of various types of stem cells in the body. Furthermore, since most if not all malignancies originate in the stem/progenitor cell compartment, cancer stem cells also express CXCR4 on their surface and, as a result, the SDF-1–CXCR4 axis is also involved in directing their trafficking/metastasis to organs that highly express SDF-1 (e.g., lymph nodes, lungs, liver and bones). Thus, Dr. Ratajczak postulates that the metastasis of cancer stem cells and trafficking of normal stem cells involve similar mechanisms. In consequence, strategies aimed at modulating the SDF-1–CXCR4 axis could have important clinical applications both in regenerative medicine to deliver normal stem cells to the tissues/organs and in clinical hematology/oncology to inhibit metastasis of cancer stem cells. The role of SDF-1-CXCR4 axis in metastasis of rhabdomyosarcoma is supported by NIH grant.

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, in collaboration with Dr. Ross, identified a novel role of C3 complement protein in retaining human hematopoietic stem cells in the bone marrow. Dr. Ratajczak 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”.

Biological effects of microvesciles. He began to study the role of membrane derived particles shed from the eukaryotic cells and their role in various aspects of hematopoiesis. Two of his R.01 grants submitted to NIH are focused on this phenomenon. 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. Investigation in Dr. Ratajczak’s laboratory is sponsored by the Kentucky Lung Cancer Foundation grant.

Optimization of stem cell engraftment. Another major interest of his research is a new hypothesis to improve engraftment of hematopoietic stem cells after transplantation by priming their sensitivity/responsiveness to SDF-1 gradient. He has identified several molecules that enhance in vitro chemoattractic responses of hematopoietic stem/progenitor cells to SDF-1 as well as accelerate in vivo engraftment of these cells after transplantation as a result of their better responsiveness and homing to SDF-1-positive niches in bone marrow.

Autocrine mechanism of hematopoiesis. Finally, Dr. Ratajczak is interested in autocrine/paracrine regulation of human hematopoiesis and in this respect about the role of HIV-autoprotective chemokines in resistance of human stem cells to HIV. This work is the subject of the R.01 grant that is currently pending at NIH.

On a routine basis Dr. Ratajczak’s laboratory isolates hematopoietic stem cells and TCSC from cord blood, mobilized peripheral blood and cadaveric bone marrow. He also has recently established a new strategy to isolate human epidermal stem cells as well as skeletal muscle stem cells.  Both keratinocytes and muscle stem cells could be used for therapeutic purposes.

Publications
Kowalska, MA, Ratajczak, MZ, Majka, M, Brass, LW, Poncz, M.  SDF-1 and MDC: complementary chemokines at the crossroads between inflammation and thrombosis. Blood 96:50-7, 2000

Majka M, Rozmyslowicz T, Honczarenko M, Ratajczak J, Wasik M, Gaulton GN, Ratajczak MZ. Biological significance of the expression of HIV related chemokine coreceptors (CCR5 and CXCR4) and their ligands by human hematopoietic cell lines. Leukemia 14:1821-32, 2000

Majka M, Janowska-Wieczorek A, Ratajczak J, Kowalska MA, Vilaire G, Pan ZK, Honczarenko M, Marquez LA, Poncz M, Ratajczak MZ. Stromal derived factor-1 and thrombopoietin regulate distinct aspects of human megakaryopoiesis. Blood 96:4142-51, 2000

Janowska-Wieczorek A, Majka M, Ratajczak J, Ratajczak MZ. Autocrine/paracrine mechanisms in human hematopoiesis. Stem Cells 19:99-107, 2001

Majka M, Janowska-Wieczorek A, Ratajczak J, Ehrenman K, Kowalska MK, 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 97:3075-85, 2001

Kijowski J, Baj M, Majka M, Reca R, Marquez LA, Christofidou-Solomidou M, Janowska-Wieczorek A, Ratajczak MZ. The SDF-1-CXCR4 axis stimulates VEGF secretion and activates integrins but does not affect proliferation and survival in lymphohematopoietic cells. Stem Cells 19:453-66, 2001

Majka M, Baj M, Kijowski J, Reca R, Ratajczak J, Ratajczak MZ.  In vitro expansion of human megakaryocytes as a tool for studying megakaryocytic development and function.  Platelets 12:325-32, 2001

Janowska-Wieczorek A, Majka M, Kijowski J, Baj-Krzyworzeka M, Reca R, Turner RA, Ratajczak J, Kowalska MA, Ratajczak MZ.  Platelet-derived microparticles bind to hematopoietic stem/progenitor cells and enhance their engraftment. Blood 98:3143-9, 2001

Machalinski B, Gontarewicz A, Ratajczak MZ. Morphological analysis of the bone marrow biopsies derived from heparinized cadaveric organ donors before and after disconnecting from the respirator. Ann Transplant 4:48-52, 2002

Janowska-Wieczorek A, Majka M, Marquez-Curtis L, Wertheim JA, Turner AR, Ratajczak MZ.  Bcr-abl-positive cells secrete angiogenic factors including matrix metalloproteinases and stimulate angiogenesis in vivo in matrigel implants. Leukemia 16:1160-6, 2002

Baj-Krzyworzeka M, Majka M, Pratico D, Ratajczak J, Vilaire G, Kijowski J, Reca R, Janowska-Wieczorek A, Ratajczak MZ.  Platelet-derived microparticles stimulate proliferation, survival, adhesion and chemotaxis of hematopoietic cells.  Exp Hematol 30:450-9, 2002

Majka M, Ratajczak J, Villaire G, Kubiczek K, Marquez LA, Janowska-Wieczorek A, Ratajczak MZ.  Thrombopoietin, but not cytokines binding to gp130 protein-coupled receptors, activates MAPKp42/44, AKT and STAT proteins in normal human CD34+ cells, megakaryocytes and platelets. Exp Hematol 30:751-60, 2002

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 100:2597-606, 2002

Majka M, Ratajczak J, Lee B, Honczarenko M, Douglas R, Kowalska MA, Silberstein L, Gewirtz AM, Ratajczak MZ. The role of HIV related chemokine receptors and chemokines in human erythropoiesis in vitro. Stem Cells 18:128-38, 2003

Ratajczak J, Kijowski J, Majka M, Jankowski K, Reca R, Ratajczak MZ. Biological significance of the different erythropoietic factors secreted by normal human eraly erythroid cells. Leuk Lymphoma 44(5):767-74, 2003

Rozmyslowicz T, Majka M, Kijowski J, Murphy SL, O’Connover D, Poncz M, Gaulton GN, Ratajczak MZ.  Platelet and megakaryocyte-derived microparticles transfer CXCR4 receptor to CXCR4-null cells and make them susceptible to infection by X4-HIV. AIDS 17:33-42, 2003

Ratajczak MZ, Majka M, Kucia M, Drukala J, Pietrzkowski Z, Peiper S, Janowska-Wieczorek A.  Expression of functional CXCR4 by muscle satellite cells and secretion of SDF-1 by muscle-derived fibroblasts is associated with the presence of both muscle progenitors in bone marrow and hematopoietic stem/progenitor cells in muscles. Stem Cells 21:363-71, 2003

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 101:3784-93, 2003

Kucia M, Wysoczynski M, Reca R, Jankowski K, Bandura L, Allendorf DJ, Zhang J, Ratajczak J, Ratajczak MZ. CXCR4-SDF-1 signaling, locomotion, chemotaxis and adhesion. Histochemical J 123;160-9, 2003

Kucia M, Ratajczak J, Reca R, Janowska-Wieczorek A, Ratajczak MZ. Tissue-specific muscle, neural and liver stem/progenitor cells reside in the bone marrow, respond to an SDF-1 gradient and are mobilized into peripheral blood during stress and tissue injury.  Blood Cells Mol Dis 32(1):52-7, 2003

Jankowski K, Kucia M, Wysoczynski M, Reca R, Zhao D, Trzyna E, Zembala M, Ratajczak J, Houghton P, Janow-ska-Wieczorek A, Ratajczak MZ.  Both HGF and SDF-1 regulate the metastatic behavior of human rhabdomyo-sarcoma cells, but only HGF enhances their resistance to radio-chemotherapy. Cancer Res 63:7926-35, 2003

Ratajczak MZ, Kucia M, Reca R, Majka M, Janowska-Wieczorek A, Ratajczak J.  Stem cell plasticity revisited: CXCR4-positive cells expressing mRNA for early muscle, liver and neural cells “hide out” in the bone marrow. Leukemia 18:29-40, 2004

Ratajczak J, Reca R, Kucia M, Majka M, Allendorf DJ, Baran JT, Janowska-Wieczorek A, Wetsel RA, Ross GD, Ratajczak MZ.  Mobilization studies in mice deficient in either C3 or C3a-receptor (C3aR) reveal a novel role for complement in retention of hematopoietic stem/progenitor cells in bone marrow.  Blood 103:2071-8, 2004

Wojakowski W, Tendera M,  Michalowska A, Majka M, Kucia M, Maslankiewicz K, Wyderka R, Ochala A, Ratajczak MZ.  The mobilization of CD34+/CXCR4+, CD34+/CD117+, c-Met+ stem cells and mononuclear cells expressing early cardiac, muscle and endothelial markers into peripheral blood in patients with acute myocardial infarction.  Circulation 110:3213-20, 2004.

Kucia M, Dawn D, Hunt G, Guo Y, Wysoczynski M,  Majka M,  Ratajczak J, Rezzoug F, Ildstad ST,  Bolli R,  Ratajczak MZ.  Cells expressing markers of cardiac tissue-committed stem cells reside in the bone marrow and are mobilized into peripheral blood following myocardial infraction.  Circ Res 95:1191-9, 2004

Wysoczynski M, Reca R, Ratajczak J, Kucia M, Shirvaikar N, Mills M, Wanzeck J, Honczarenko M, Janowska- Wieczorek A, Ratajczak MZ. Incorporation of CXCR4 into membrane lipid rafts primes homing-related responses of hematopoietic stem cells to an SDF-1 gradient.  Blood 105(1):40-8, 2005

Kucia M, Ratajczak J, Ratajczak MZ.  Bone marrow as a source of circulating CXCR4+ tissue-committed stem cells.  Biol Cell 97(2):133-46, 2005

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(5):752-60, 2005

Cramer DE, Allendorf D, Baran JT, Hansen R, Marroquin J, Li B, Ratajczak J, Ratajczak MZ, Yan J.  Beta-Glucan enhances complement-mediated hematopoietic recovery after bone marrow injury.  Blood 107:835-40, 2006.

Kucia M, Zhang PY, Reca R, Wysoczynski M, Machalinski B, Ildstad ST, Ratajczak J, Shields CB, Ratajczak MZ.  Cells enriched in markers or neural tissue-committed stem cells (TCSC) reside in the bone marrow and are mobilized into the peripheral blood following stroke.  Leukemia 20:18-28, 2006

Baj-Krzyworzeka M, Szatanek R, Weglarczyk K, Baran J, Urbanowicz B, Branski P, Ratajczak MZ, Zembala M
.  Tumour-derived microvesicles carry several surface determinants and mRNA of tumour cells and transfer some of these determinants to monocytes.  Cancer Immunol Immunother 55:808-18, 2006

Huang Y, Kucia M, Rezzoug F, Ratajczak J, Tanner MK, Ratajczak MZ, Schanie CL, Xu H, Fugier Vivier I, Ildstad ST.  FL-mobilized peripheral blood but not FL-expanded bone marrow FC promote establishment of chimerism and tolerance.  Stem Cells 4:936-48, 2006


Ratajczak MZ, Reca R, Wysoczynski M, Yan J, Ratajczak J.  Modulation of the SDF-1-CXCR4 axis by the third complement component (C3) - Implications for trafficking of CXCR4+ stem cells.  Exp Hematol 34:986-95, 2006

Ratajczak J, Miekus K, Kucia M, Zhang J, Reca R, Dvorak P, Ratajczak MZ. Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery.  Leukemia 20:847-56, 2006

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 20:857-69, 2006

Ratajczak MZ, Kucia M, Dobrowolska H, Wanzeck J, Reca R, Ratajczak J.  Emerging concept of cancer as a stem cell disorder.  CEJB 1:73-87, 2006

Kucia M, Ratajczak MZ.  Stem cells as a two edged sword – from regeneration to tumor formation.  J Phys Pharm 57(Suppl)7:5-16, 2006

Ratajczak J, Wysoczynski M, Hayek F, Janowska-Wieczorek A, Ratajczak MZ.  Membrane-derived microvesicles (MV): Important and underappreciated mediators of cell-to-cell communication.  Leukemia 20:1487-95, 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

Ratajczak MZ, Zuba-Surma E, Kucia M, Reca R, Wojakowski W, Ratajczak J.  The pleiotropic effects of the SDF-1-CXCR4 axis in organogenesis, regeneration and tumorogenesis.  Leukemia 20:1915-24, 2006

Majka M, Drukala J, Lesko E, Wysoczynski M, Jenson AB, Ratajczak MZ.  SDF-1 alone and in co-operation with HGF regulates biology of human cervical carcinoma cells.  Folia Histochem Cytobiol 44:155-64, 2006

Zaucha-Prazmo A, Drabko K, Wojcik B, Choma M, Kalwak K, Gorczynska E, Turkiewicz D, Slociak M, Ussowicz M, Dyla A, Chybicka A, Gozdzik J, Ratajczak M, Styczynski J, Debski R, Wysocki M, Kowalczyk J.  (Polish) High-dose therapy followed by auto HSCT in children with advanced neuroblastoma in four transplant centres in Poland.  Med Wieku Rozwoj 10:775-84, 2006

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 (VSEL) cells purified from human cord blood – preliminary report.  Leukemia 21:297-303, 2007

Wysoczynski M, Miekus K, Jankowski K, Wanzeck J, Janowska-Wieczorek A, Ratajczak J, Ratajczak MZ. Leukemia Inhibitory Factor: A newly identified metastatic factor in rhabdomyosarcomas.  Cancer Res 67:2131-40, 2007

Ratajczak MZ, Machalinski B, Wojakowski W, Kucia M.  A hypothesis for an embryonic origin of pluripotent Oct-4+ stem cells in adult bone marrow and other tissues.  Leukemia 21(5):860-7, 2007. Review.

Reca R, Cramer D, Yan J, Laughlin MJ, Janowska-Wieczorek A, Ratajczak J, Ratajczak MZ.  A novel role of complement in mobilization: immunodeficient mice are poor granulocyte-colony stimulating factor mobilizers because they lack complement-activating immunoglobulins.  Stem Cells 25(12):3093-100, 2007

Ratajczak MZ, Zuba-Surma EK, Shin DM, Ratajczak J, Kucia M.  Very small embryonic-like (VSEL) stem cells in adult organs and their potential role in rejuvenation of tissues and longevity.  Exp Gerontol. 2008 Jun 14. [Epub ahead of print]

Kucia MJ, 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 26(8):2083-92, 2008

Ratajczak MZ, Zuba-Surma EK, Wysoczynski M, Ratajczak J, Kucia M.  Very small embryonic-like stem cells: characterization, developmental origin, and biological significance.  Exp Hematol 36(6):742-51, 2008. Review.

Ratajczak MZ, Zuba-Surma EK, Machalinski B, Ratajczak J, Kucia M.  Very small embryonic-like (VSEL) stem cells: purification from adult organs, characterization, and biological significance.  Stem Cell Rev 4(2):89-99, 2008

Ratajczak MZ, Zuba-Surma EK, Wysoczynski M, Wan W, Ratajczak J, Wojakowski W, Kucia M.  Hunt for pluripotent stem cell -- regenerative medicine search for almighty cell.  J Autoimmun 30(3):151-62, 2008. Review.

Kucia M, Zuba-Surma EK, Wysoczynski M, Wu W, Ratajczak J, Machalinski B, Ratajczak MZ.  Adult marrow-derived very small embryonic-like stem cells and tissue engineering.  Expert Opin Biol Ther 7(10):1499-514, 2008. Review.

Wysoczynski M, Ratajczak J, Reca R, Kucia M, Ratajczak MZ.  The third complement component as modulator of platelet production.  Adv Exp Med Biol 598:226-39, 2007. Review.

Kucia M, Wysoczynski M, Ratajczak J, Ratajczak MZ.  Identification of very small embryonic like (VSEL) stem cells in bone marrow.  Cell Tissue Res 331(1):125-34, 2008

Contact Information

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Louisville, KY 40202
(502)-852-1788


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