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Christopherson
Kent
W.
PhD
Associate Professor
Anatomy and Cell Biology, Immunology-Microbiology, Internal Medicine
Graduate College, Rush Medical College
1725 W. Harrison St.
Professional Office Building
Ste. 834
Chicago, IL 60612

1725 W. Harrison St.
Professional Office Building
Ste. 1587
Chicago, IL 60612

(312) 563-2522
(312) 563-2523
kent_christopherson@rush.edu
PhD, Indiana University School of Medicine, 2001

BS, Bradley University, 1997

Biological Phenomena Cell Phenomena and Immunity, Biological Sciences, Hemic and Lymphatic Diseases, Neoplasms
Animal surgery/Modeling, Cytokine Assessment, Flow Cytometry, Gene Chip Technologies, Immunohisto-/immunocytochemistry, Microscopy (Electron Transmission Fluorescence Confocal), PCR, Real-time PCR, Transgenic Animal Technology/Microinjection, Western Northern Southern Blotting


Dr. Christopherson's translational research interests encompass the analysis of normal and neoplastic experimental hematology, stem cell biology, umbilical cord blood biology, and regulation of hematopoietic stem cell transplantation.

Dr. Christopherson obtained his BS degree?in 1997 from Bradley University, Peoria, IL. In 2001, he received his PhD in biochemistry and molecular biology with a minor in medical & molecular genetics from Indiana University School of Medicine, Indianapolis, Ind., following the completion of his dissertation in the laboratory of Rob A. Hromas, MD, Division of Hematology/Oncology. His postdoctoral training in experimental hematology and stem cell biology, 2001-2003, was in the lab of Hal Broxmeyer, PhD, in the Department of Microbiology and Immunology at Indiana University School of Medicine and the Walther Oncology Center, Indianapolis, Ind. During this time, Dr. Christopherson was supported sequentially by a National Institutes of Health - National Research Service Awards (NRSA) Training Grant and a Leukemia & Lymphoma Society Career Development Program Fellow Award. From 2003-2006 Dr. Christopherson held the appointment of assistant professor at the Institute of Molecular Medicine, at The University of Texas, Houston.

Dr. Christopherson joined Rush in September?2003 as an assistant professor in the Section of Hematology and Stem Cell Transplantation, Division of Hematology/Oncology, Department of Medicine with a conjoint appointment in the Department of Immunology/ Microbiology at Rush University Medical Center. Dr. Christopherson's laboratory leads translational research, from the laboratory bench to the clinical patient bedside, for the Section of Hematology and Stem Cell Transplantation. He is most well known in the scientific field of blood stem cell transplantation for his contributions to the identification and validation of novel methods to improve stem cell transplant efficiency. This accomplishment is represented in his 2004 manuscript in Science magazine. Dr. Christopherson holds memberships in the American Association of Blood Banks, American Association of Blood & Marrow Transplantation, American Society of Hematology, International Society for Experimental Hematology, American Association of Immunologists, International Society for Cellular Therapy, International Society for Stem Cell Research, and Sigma Xi.

Dr. Christopherson's primary research interests are directed at novel methods of increasing stem cell transplant efficiency. As one component of this project, the lab studies, collection, banking, and transplantation of umbilical cord blood stem cells for clinical and research purposes. Umbilical cord blood, along with bone marrow and mobilized peripheral blood, is a validated source of blood stem cells for the treatment of blood cancers. Originally established as being useful for treatment of children, cord blood is now being extended to the treatment of adult blood cancers, including leukemia, lymphoma, and myeloma, Umbilical cord blood is collected from the umbilical cord after the delivery of a baby and separation of the umbilical cord from the baby. Currently, the majority of cord blood samples across the United States and in Chicago are discarded into the trash along with the placenta and the umbilical cord without recognition of the life saving potential of this blood for severe hematologic diseases.

An additional component of Dr. Christopherson's research project is to develop an understanding of the events involved in mediating the homing and subsequent engraftment of hematopoietic stem and progenitor cells into the patients bone marrow during transplantation and mobilization of hematopoietic stem and progenitor cells out of the bone marrow during cytokine treatment thereby allowing the clinical collection of peripheral blood stem cells. In these research efforts, much of the work has been focused on the role that chemokines and their regulators play in the trafficking of stem cells. Chemokines act through chemokine receptors, which are a subfamily of G-protein coupled seven-transmembrane receptors. The chemokine CXCL12 (also known as stromal cell-derived factor 1/SDF-1) has been shown to chemoattract hematopoietic stem and progenitor cells and is believed to be important in the trafficking of hematopoietic stem and progenitor cells. The N-terminus of chemokines interacts with the extracellular portion of chemokine receptors and conveys much of the specificity for receptor binding. Consequently, the removal of the N-terminal amino acids results in significant changes in receptor binding and/or functional activity. CD26 (DPPIV/dipeptidylpeptidase IV) is an extracellular peptidase that cleaves dipeptides from the N-terminus of polypeptide chains after a proline or an alanine. CXCL12 has been shown to be truncated by CD26 and Dr. Christopherson's lab investigates CD26 as a negative regulator of CXCL12 and thereby a negative regulator of hematopoietic stem and progenitor cell homing and engraftment.

The overall goal of our research program for the next five years is to increase our understanding of the specific and overall roles that chemokines and the peptidases that regulate them play in hematopoietic stem and progenitor cell homing, engraftment, and mobilization. Utilizing human clinical samples and mouse models of transplantation we hope to identify endogenous negative regulators of transplant homing and engraftment. In doing so, we hope to have also identified targets for improving transplant efficiency. Transplant efficiency has become an important consideration in instances of limiting donor cell numbers, due to adverse effects on clinical outcome. Since it is believed that not all hematopoietic stem and progenitor cells home to the appropriate bone marrow niches necessary for engraftment, a means of increasing the number of cells reaching the recipient's bone marrow would be to enhance the efficiency of hematopoietic stem and progenitor cell homing and subsequent engraftment. This area of translational research has important implications for the treatment of blood cancers that utilize stem cell transplantation a treatment option.

See CV

Selected Publications

Christopherson KW 2nd, Campbell JJ, Hromas R. Transgenic Over-Expression of the CC Chemokine CCL21 Disrupts T-cell Migration. Blood 2001 Dec 15; 98(13): 3562-3568.

Christopherson KW 2nd, Hangoc G, Broxmeyer HE. Cell Surface Peptidase CD26/Dipeptidylpeptidase IV Regulates CXCL12/Stromal Cell-Derived Factor-1-Mediated Chemotaxis of Human Cord Blood CD34+ Progenitor Cells. J Immunol 2002 Dec 15; 169(12): 7000-8.

Christopherson KW 2nd, Campbell JJ, Travers JB, Hood AF, Ramsey HC, Hromas R. Endothelial Induction of the T-Cell Chemokine CC21 in T-cell Auto-Immune Diseases. Blood 2003 Feb 1; 101(3): 801-6.

Christopherson KW 2nd, Cooper S, Broxmeyer HE. Cell Surface Peptidase CD26/DPPIV Mediates G-CSF Mobilization of Mouse Progenitor Cells. Blood 2003 Jun 15; 101(12): 4680-6.

Christopherson KW 2nd, Cooper S, Hangoc G, Broxmeyer HE. CD26 is Essential for Normal G-CSF-induced Progenitor Cell Mobilization as Determined by CD26-/- Mice. Exp Hematol 2003 Nov; 31(11): 1126-34.

Christopherson KW 2nd, Hangoc G, Mantel CR, Broxmeyer HE. Modulation of Hematopoietic Stem Cell Homing and Engraftment by CD26. Science 2004; 305:1000-3.

Porecha NK, English K, Hangoc G, Broxmeyer HE, Christopherson KW 2nd. Enhanced Functional Response to CXCL12/SDF-1 through Retroviral Over-expression of CXCR4 on M07e cells: Implications for Hematopoietic Stem Cell Transplantation. Stem Cells Dev. 2006 Jun; 15(3): 325-33.

Christopherson KW 2nd, Uralil SE, Porecha NK, Zabriskie RC, Kidd SM, Ramin SM. G-CSF and GM-CSF Induced Up-regulation of CD26 Peptidase Down-Regulates the Functional Chemotactic Response of CD34+CD38- human Cord Blood Hematopoietic Stem Cells. Exp Hematol. 2006 Aug; 34(8): 1060-8.

Christopherson KW 2nd, Paganessi L, Napier S, Porecha N. CD26 Inhibition on CD34+ or lineage- human Umbilical Cord Blood Donor HSC/HPC Improves Long-Term Engraftment into NOD/SCID/Beta2null Immunodeficient Mice. Stem Cells Dev. 2007 Jun; 16(3): 355-60.

Selected Reviews and Book Chapters

Christopherson KW 2nd, Hromas R. Chemokine regulation of normal and pathologic immune responses. Stem Cells 2001; 19(5): 388-396.

Christopherson KW 2nd, Broxmeyer HE. Hematopoietic Stem & Progenitor Cell Homing, Engraftment, & Mobilization In the context of the CXCL12/SDF-1 ? CXCR4 Axis. In: Cord Blood: Biology, Immunology, Banking, and Clinical Transplantation. Broxmeyer HE (ed.) Bethesda, MD: American Assoc. Blood Banking Press; Chapter 4, 2004.

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