Mariusz Z. Ratajczak, MD, PhD, DSci

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)

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 an

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