Mar 15 “The Novel Role of Complement Cascade and Bioactive Phosphosphingolipids in Trafficking of Hematopoietic Stem Cells” by Mariusz Ratajczak

March 15, 2017 by Health System Enterprise Calendar

[Pinn Hall Rm. 5023] Hosted by Kevin Lynch, Mariusz Z. Ratajczak is the Professor of Department of Medicine at the University of Louisville School of Medicine and the Director of Stem Cell Program, James Graham Brown Cancer Center Stella and Henry Hoenig Endowed Chair in Cancer Biology. He is an Associate Member of Bone Marrow Transplant Program, University of Louisville School of Medicine and an Associate Member of the Department of Immunology and Microbiology, University of Louisville School of Medicine.

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.