Paul W. Kincade, Ph.D.
OMRF Vice President of Research
William H. and Rita Bell Chair in Biomedical Research
Adjunct Professor, Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center
Scientific Director, Oklahoma Center for Adult Stem Cell Research
The research in my laboratory focuses on the development of the immune system. That is, we are learning how highly specialized cells that we call “soldiers of the immune system” are produced. Formally called lymphocytes, these cells are produced in two types of factories: the bone marrow and thymus. Lymphocytes migrate throughout the body and work together in teams to keep us healthy. However, they eventually grow tired and must constantly be replaced. We have learned that they are produced in large numbers throughout life and have discovered that many proteins and hormones such as estrogen are responsible for carefully controlling lymphocyte production. Abnormalities in this vital process result in immune deficiency diseases, autoimmunity and cancers such as leukemias and lymphomas.
We recently discovered new cell types that we believe have very special jobs in the immune system. Additionally, our research team found a new way the body springs into action during times of infection. We discovered that even stem cells can recognize bacterial and viral products. Stem cells in bone marrow quickly respond by producing new cells that function in what is called “innate immunity.” This represents an important new way the bone marrow can replenish our first lines of defense. On the other hand, we have new evidence that chronic infections may prematurely age the immune system. Further study should reveal how the process works and might suggest ways to protect against one kind of age-related deterioration.
B.S., Mississippi State University, 1966
M.S., Mississippi State University, 1968
Ph.D., University of Alabama, 1971
Honors and Awards
1969-1971 National Institutes of Health Predoctoral Fellowship
1971-1972 National Institutes of Health Postdoctoral Fellowship
1972-1975 Arthritis Foundation Postdoctoral Fellowship
1975-1978 Arthritis Foundation Senior Investigatorship
1978-1983 National Institutes of Health Research Career Development Award
1989 M.E.R.I.T. Award (National Institutes of Health)
1992 William H. and Rita Bell Chair for Biomedical Research
1997-2003 Councilor, American Association of Immunologists
1998 Distinguished Service Award, American Association of Immunologists
1998-2006 Board, Federation of American Societies for Experimental Biology
1999-2004 International Union of Immunological Societies
2000-2002 Chair, FASEB Science Policy Subcommittee on Training and Careers
2002-2003 President, American Association of Immunologists
2002-2003 Chair, FASEB Science policy committee
2004-2005 President, Federation of American Societies for Experimental Biology
2004- Board of Scientific Councilors, National Institute for Child Health & Human Development
2005- Scientific Advisory Board, RIKEN Institute for Allergy & Immunology
2006 – ISI List of Highly Cited Scientists
Editorial boards of numerous scientific journals; faculty for courses in immunology in U.S. and abroad; ad hoc advisor to Veterans Administration, American Cancer Society, National Foundation – March of Dimes, National Science Foundation (Cellular Physiology Program), National Institutes of Health (National Cancer Institute, National Institute on Aging, and the Immunobiology Study Section); program chair, American Association of Immunologists.
American Association of Immunologists
American Society for Investigative Pathology
International Society for Experimental Hematology
Clinical Immunology Society
American Society of Hematology
Joined OMRF Scientific Staff in 1982.
An understanding of leukemias, lymphomas, immunodeficiency and autoimmune diseases requires fundamental information about immune system development. In addition, hematopoietic stem cells (HSC) represent an excellent model for studying stem cell properties, plasticity and utility for tissue regeneration. Our laboratory explores developmental relationships between HSC and progenitors of B, T, NK and plasmacytoid dendritic cells.
High-speed cell sorting and RAG-1/GFP knock-in mice are being exploited to identify the most primitive of lymphoid progenitors in fetal and adult tissues. We can identify even earlier lymphopoietic cells in E8.5 embryos and direct them to B or T lineage fates by differential ligation of Notch family receptors. Additionally, we have charted and extensively characterized the first waves of B and T lymphocyte formation. Fetal and adult lymphoid progenitors are quite different in many respects, and we are trying to determine if adult progenitors can reacquire fetal characteristics.
Adult bone marrow contains plasmacytoid dendritic cells (pDC), a population that has attracted considerable interest because of their exceptional ability to produce type I interferon. We have recently studied their turnover, determined their origins and found that there are actually two, functionally distinct subsets of pDC. While both diverge from HSC at a very early stage and are developmentally unrelated to T lymphocytes, one shares a number of properties with B cells. Since pDC are thought to participate in regulation of immune responses and autoimmune disease, it will now be important to attribute these functions to one of the subsets.
Blood cell formation has traditionally been described in terms of a series of binary fate decisions. Recent findings are not compatible with that view, and a new model was constructed to describe lympho-hematopoiesis. It appears that HSC progressively and gradually lose differentiation options. Their progeny have more plasticity than previously thought and can be reprogrammed to different fates. In fact, we now believe this may happen during life-threatening infections.
Vadillo E, Dorantes-Acosta E, Arriaga-Pizano L, Chavez-Gonzalez A, Reyes-Maldonado E, Garrett KP, Mayani H, Kincade PW, Pelayo R. Adult, but not Neonatal, Human Lymphoid Progenitors Respond to TLR9 Ligation by Producing Functional NK-like Cells. Exp Hematol 42:562-573, 2014. [Abstract]
Iida R, Welner RS, Zhao W, Alberola-Ila J, Medina KL, Zhao ZJ, Kincade PW. Stem and Progenitor Cell Subsets Are Affected by JAK2 Signaling and Can Be Monitored by Flow Cytometry. PLoS One 9:e93643, 2014. [Abstract]
Zhang Q, Esplin BL, Iida R, Garrett KP, Huang ZL, Medina KL, Kincade PW. RAG-1 and Ly6D Independently Reflect Progression in the B Lymphoid Lineage. PLoS One 8:e72397, 2013. [Abstract]
* Ichii M, Frank MB, Iozzo RV, Kincade PW. The canonical Wnt pathway shapes niches supportive for hematopoietic stem/progenitor cells. Blood 119:1683-1692, 2012. [Abstract]
Zhang Q, Iida R, Shimazu T, Kincade PW. Replenishing B lymphocytes in health and disease. Curr Opin Immunol 24:196-203, 2012. [Abstract]
Esplin BL, Shimazu T, Welner RS, Garrett KP, Nie L, Zhang Q, Humphrey MB, Yang Q, Borghesi LA, Kincade PW. Chronic exposure to a TLR Ligand injures hematopoietic stem cells. J Immunol 186:5367-5375, 2011. [Abstract]
Ichii M, Shimazu T, Welner RS, Garrett KP, Zhang Q, Esplin BL, Kincade PW. Functional diversity of stem and progenitor cells with B-lymphopoietic potential. Immunol Rev. 237:10-21, 2010. [Abstract]
Shimazu T, Iida R, Zhang Q, Welner RS, Medina KL, Alberola-Ila J, Kincade PW. CD86 is expressed on murine hematopoietic stem cells and denotes lymphopoietic potential. Blood 119:4889-4897, 2012. [Abstract]
Welner RS, Esplin BL, Garrett KP, Pelayo R, Luche H, Fehling HJ, Kincade PW. Asynchronous RAG-1 expression during B lymphopoiesis. J Immunol. 183:7768-7777, 2009. [Abstract]
Immunobiology and Cancer Research Program, MS 23
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-7905
Fax: (405) 271-8568