G. Rafael Fernandez-Botran, Ph.D.

Education:G. Rafael Fernandez-Botran, Ph.D.

B.S., Biological Chemistry, Universidad de San Carlos de Guatemala, Guatemala; 1979
Ph.D., Microbiology and Immunology, University of Kansas Medical Center, Kansas City, KS; 1985
Postdoctoral Fellowship, Department of Microbiology & Immunology, University of Texas Southwestern Medical Center, Dallas TX; 1985-1992

Curriculum Vitae

Current Positions:

Associate Professor; Department of Pathology & Laboratory Medicine
Associate Faculty, Department of Microbiology & Immunology

Contact Information:

MDR Building, Room 217A
University of Louisville Health Sciences Center
511 South Floyd Street
Louisville, KY 40292
Phone: 502-852-5375
Fax:  502-852-1177

Email: grfern01@louisville.edu

Website Link(s):


Research Description:

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 convenient target for anti-inflammatory or immunomodulatory therapies. Currently, the effects of inhibitors of cytokine-GAG interactions are being studied in several experimental animal models.

Effect of HIV status on the development of non-alcoholic fatty liver disease (NAFLD) in women. Liver disease remains a leading cause of mortality among HIV-infected patients, particularly those from vulnerable populations, including women and minorities. While the current availability of antiviral therapies has contributed to decreased morbidity and mortality, non-alcoholic fatty liver disease (NAFLD) and its progressive forms, non-alcoholic steatohepatitis (NASH) and fibrosis, have become an increasingly frequent cause of liver disease and new challenge in the management of HIV-infected patients. The goal of this project is to investigate potential mechanisms whereby HIV infection may foster the risk of NAFLD and progression to NASH and fibrosis in women.

Stress-related inflammation.   It has become clear that life stress and adversity lead to elevated systemic inflammation and resulting morbidity.  While stress-reduction methods are being considered for lowering inflammation, a major limitation for any approach has been the lack of availability of an accurate readout of the inflammation-produced by stress and adversity. Our goal is to develop more accurate measures of stress-related inflammation, based particularly on the IL-6-signaling pathways, so that it may be possible to better identify and intervene in the specific mechanisms responsible for stress-related disease. 

Representative Publications:

IL-4 stimulates the proliferation of T cells and has a role in the cross-regulation Th1 and Th2 subsets.

Fernandez‑Botran R, Krammer PH, Diamantstein T, Uhr JW, Vitetta ES.   B cell‑stimulatory factor 1 (BSF‑1) promotes growth of helper T cell lines.   Journal of Experimental Medicine 1986 Aug 1;164(2):580‑93. PMID: 2941517.  PMCID: PMC2188229.

Fernandez‑Botran R, Sanders VM, Oliver KG, Chen Y-W, Krammer PH,  Uhr JW, Vitetta ES.   Interleukin 4 mediates autocrine growth of helper T cells after antigenic stimulation.  Proceedings of the National Academy of Science USA 1986 Dec;83(24):9689‑93.  PMID: 2948185.  PMCID: PMC387206.

Fernandez‑Botran R, Sanders VM, Mosmann TR, Vitetta ES.  Lymphokine‑mediated regulation of the proliferative response of clones of T helper 1 and T helper 2 cells.  Journal of Experimental Medicine 1988 Aug 1;168(2):543‑58.  PMID: 2970518.  PMCID: PMC2189014.

Convergence of IL2 and IL-4 Pathways.

Fernandez-Botran R, Sanders VM, Vitetta ES.  Interactions between receptors for interleukin 2 and interleukin 4 on lines of helper T cells (HT‑2) and B lymphoma cells (BCL1).  Journal of Experimental Medicine 1989 Feb 1;169(2):379‑91. PMID: 2521354.  PMCID: PMC2189212.

Existence and characterization of soluble IL-4 receptors (sIL-4R).

Fernandez‑Botran R, Vitetta ES.  A soluble, high affinity IL‑4‑ binding protein is present in the biological fluids of mice.  Proceedings of the National Academy of Science USA 1990 Jun;87(11):4202‑6. PMID: 2349230.  PMCID: PMC54076.

Fernandez‑Botran R, Vitetta ES. Evidence that natural murine soluble IL‑4 receptors may act as transport proteins.  Journal of Experimental Medicine 1991 Sep 1;174(3):673-81.  PMID: 1875167.  PMCID: PMC2118951.

Chilton PM, Fernandez-Botran R.  The production of soluble interleukin-4 receptors by murine spleen cells is regulated by T cell activation and interleukin-4.  Journal of Immunology 1993 Dec 1;151(11):5907-17.  PMID: 8245438.

Fernandez-Botran R, Chilton PM, Ma Y, Windsor JL, Street NE.  Control of the production of soluble interleukin-4 receptors: implications in immunoregulation.  Journal of Leukocyte Biology 1996 Apr;59(4):499-504. Review.  PMID: 8613696.

Ma Y,Hurst HE, Fernandez-Botran R. Soluble cytokine receptors as carrier proteins: the effects of soluble IL-4 receptors on the pharmacokinetics of murine IL-4.  Journal of Pharmacology & Experimental Therapeutics 1996 Oct;279(1):340-50.  PMID: 8859012.

Targeting of interactions of cytokines/chemokines with glycosaminoglycans (GAGs) as an immunotherapeutic approach.

Fernandez-Botran R, Yan J, Justus DE. Binding of interferon-γ by glycosaminoglycans: a strategy for localization and/or inhibition of its activity.  Cytokine 1999 May;11(5):313-25.  PMID: 10328871.

Fernandez-Botran R, Gorantla V, Sun X, Ren X, Perez-Abadia G, Crespo FA, Oliver R, Orhun HI, Maldonado C, Ray M, Barker JH.  Targeting of glycosaminoglycan-cytokine interactions as a novel therapeutic approach in composite tissue allotransplantation.  Transplantation 2002 Sep 15;74(5):623-9.  PMID: 12352877.

Fernandez-Botran R, Romanovskis P, Sun X, Spatola AF.  Linear basic peptides for targeting interferon--glycosaminoglycan interactions.  Synthesis and inhibitory properties.   Journal of Peptide Research 2004 Feb;63(2):56-62. PMID: 15009526.

Cripps J, Crespo FA, Romanovskis P, Spatola A, Fernandez-Botran R.  Modulation of acute inflammation by targeting glycosaminoglycan-cytokine interactions.  International Immunopharmacology 2005 Oct;5(11):1622-32.  PMID: 16039552.

Crespo FA, Sun X, Cripps JG, Fernandez-Botran R.  The immunoregulatory effects of gangliosides involve immune deviation favoring type-2 T cell responses.  Journal of Leukocyte Biology 2006 Mar;79(3):586-95.  PMID: 16415169.

Characterization of cytokine and inflammatory profiles in infectious and neurodegenerative diseases as well as in psychobiological alterations.  

Fernandez-Botran R, Ahmed Z,Crespo F, Gatenbee C,Gonzalez J, Dickson DW, Litvan I.  Cytokine expression and microglial activation in progressive supranuclear palsy.  Parkinsonism Related Disorders 2011 Nov;17(9):683-8.  PMID: 21741294.  PMCID: PMC3196843.

Fernandez-Botran, R, Miller JJ, Burns VE, Newton TL.  Correlations among inflammatory markers in plasma, saliva and oral mucosal transudate in post-menopausal women with past intimate partner violence.  Brain Behavior & Immunity 2011 Feb;25(2):314-21.  PMID: 20888902.  PMCID: PMC3025073.

Bordon J, Plankey M, Young M, Greenblatt RM, Villacres MC, French AL, Zhang J, Brock G, Appana S, Herold B, Durkin H, Golub JE, Fernandez-Botran R.  Lower levels of interleukin-12 precede tuberculosis among HIV-infected women.  Cytokine 2011 Nov;56(2):325-31.  PMID: 21880503.  PMCID: PMC3466167.

Fernandez-Botran R, Uriarte SM, Arnold FW, Rodriguez-Hernandez L, Rane MJ, Peyrani P, Wiemken T, Kelley R, Uppatla S, Cavallazzi R, Blasi F, Morlacchi L, Aliberti S, Jonsson C, Ramirez JA, Bordon J. Contrasting inflammatory responses in severe and non-severe community-acquired pneumonia.  Inflammation 2014 Aug;37(4):1158-66.  PMID: 24557760.

Szabo YZ, Newton TL, Miller JJ, Lyle KB, Fernandez-Botran R.  Acute stress induces increases in salivary IL-10 levels.  Stress 2016 Sep;19(5):499-505.  PMID: 27353112.

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