Email Rafael Fernandez - Botran
Phone Numbers: (502) 852-5375 (Office)
Fax Number: (502) 852-1177
Address:
     Division of Research
     Department of Pathology & Laboratory Medicine
     School of Medicine
     University of Louisville
     Louisville, KY, 40292
Ph. D. 1985, University of Kansas

Research Interests:

Cytokines, potent regulatory proteins produced by leukocytes and other cell types, play a central role in both health and disease by mediating many physiologic processes, including inflammation, hemopoiesis and immune responses. The research goals of our laboratory are to understand the mechanisms that control the activity of cytokines in vivo and to develop novel immunotherapeutic approaches to the treatment of disease, based on the inhibition or enhancement of cytokine activity. Current projects in our laboratory are:

• Targeting glycosaminoglycan-cytokine interactions as an immunotherapeutic approach. Interactions between cytokines and glycosaminoglycans (GAGs) on cell membranes or the extracellular matrix are important in the development of local inflammation and immune responses and may constitute a valid target for anti-inflammatory or immunomodulatory therapies. Currently, the effects of inhibitors of cytokine-GAG interactions are being studied in several experimental animal models, including cardiac arrest-induced brain damage, and peritoneal inflammation.

• Immunoregulatory effects of gangliosides and potential role in immune escape mechanisms by tumor cells. Gangliosides are sialic acid-containing glycolipids found in the plasma membranes of all cells, but particularly enriched in the central nervous system and in certain tumor cells. Gangliosides have immunosuppressive activities and may be responsible for tumor-induced immunosuppression. Our laboratory is investigating the mechanisms responsible for the suppressive effects of gangliosides, particularly their effects on the normal differentiation of helper T cells and cytokine receptor signaling.

Selected Publications:

1. Fernandez-Botran, R., P. Romanovskis, X. Sun, and A. F. Spatola.  2004.  Linear basic peptides for targeting interferon--glycosaminoglycan interactions.  Synthesis and inhibitory properties.  J. Peptide Res., 63:56-62.
2. Carr, L., A. Tucker, and R. Fernandez-Botran.  2003.  The enhancement of T cell proliferation is mediated peripherally and does not involve interleukin 2.  J. Neuroimmunol., 142:166-169.
3. Carr, L., A. Tucker, and R. Fernandez-Botran.  2003.  In vivo administration of L-DOPA or dopamine decreases the number of splenic IFN-producing cells.  J. Neuroimmunol., 137:87-93.
4. Fernandez-Botran, R., V. Gorantla, X. Sun, X. Ren, G. Perez-Abadia, F. A. Crespo, R. Oliver, H. I.  Orhun, C. Maldonado, M. Ray, and J. H. Barker.  2002.  Targeting of glycosaminoglycan-cytokine interactions as a novel therapeutic approach in composite tissue allotransplantation.  Transplantation, 74:623-629.
5. Fernandez-Botran, R., F. A. Crespo, and X. Sun.  2002.  Soluble cytokine receptors in biological therapy.  Exp. Opin. Biol. Ther., 2:585-605.
6. Fernandez-Botran, R.  2001.  A small-molecule antagonist of human and murine CCR1 receptors.  Exp. Opin. Invest. Drugs, 10:1387-1389.
7. Fernandez-Botran, R.  2000.  Soluble cytokine receptors: novel immunotherapeutic agents.  Exp. Opin. Invest. Drugs, 9:497-514.
8. Fernandez-Botran, R.  1999.  Soluble cytokine receptors: basic immunology and clinical applications.  Crit. Rev. Clin. Lab. Sci., 36:165-224.
9. Fernandez-Botran, R., P. M. Chilton, B. D. Hondowicz, J. Vetvickova, J. Yan, W. Jones III, and P. A. Scott.  1999.  Regulation of the production of soluble IL-4 receptors in murine cutaneous leishmaniasis.  The roles of IL-12 and IL-4. J. Leukocyte Biol.  66:481-488.
10. Shirbacheh, M. V., X. Ren, J. W. Jones, W. C. Breidenbach, A. W. Jevans, R. Fernandez-Botran, C. Maldonado, J. H. Barker, and S. A. Gruber.  1999.  Pharmacokinetic advantage of intraarterial cyclosporine A delivery to the vascularly-isolated  rabbit forelimb.  J. Pharmacol. Exp. Ther. 289:1185-1190.
11. Fernandez-Botran, R., J. Yan, and D. E. Justus.  1999.  Binding of interferon-γ by glycosaminoglycans: a strategy for localization and/or inhibition of its activity. Cytokine.  11:313-325.