Astrid Cardona Ph.D Affiliation: University of Texas at San Antonio Biology "Infectious and Immunological Diseases","Other" Title: Associate Professor Rank: Tenured Address: One UTSA Circle MBT 1.212 San Antonio, TX 78249 Contact: Email: [email protected] Telephone: 2104585071 Narrative Studies in Dr. Cardona's lab use experimental autoimmune encephalomyelitis (EAE) as a model to investigate pathological events related to Multiple Sclerosis. The primary focus is to determine the contribution of the fractalkine receptor (CX3CR1) to disease severity. Fractalkine (CX3CL1) and its receptor CX3CR1 provide a physiologically-relevant neuron-microglia communication mechanism. Fractalkine is a unique central nervous system (CNS) chemokine present on neuronal membranes and capable of being released as a soluble protein by constitutive or stress-activated ADAM-family protease activity. Fractalkine exerts its functions by binding to CX3CR1 on microglial cells. Although they are mainly produced in the CNS, Fractalkine and CX3CR1 also have a distinctive peripheral pattern of expression. Fractalkine is found at low levels in endothelial and some epithelial cells of selected tissues such as kidney, lung, prostate and heart, but not spleen or liver. CNS endothelial cells do not express fractalkine. Circulating monocytes, dendritic cells and NK cells express CX3CR1. In vitro studies suggested that soluble fractalkine mediates microglial chemoattraction but, surprisingly inhibits microglial activation, and protects microglia from apoptosis. The lab intends to clarify the role of fractalkine/CX3CR1 in the brain, research that is instrumental for potential development of therapeutic agents. Some of the questions they are addressing include: Does CX3CR1 play a role in the trafficking of microglial precursors? Does CX3CR1-deficiency on microglia or peripheral cells enhance neuronal/axonal pathology? How does CX3CR1-deficiency alter CNS immune responses? Publications 1. Cardona SM, Mendiola AS, Yang YC, Adkins SL, Torres V, Cardona AE. Disruption of PubMed Fractalkine Signaling Leads to Microglial Activation and Neuronal Damage in the Diabetic Retina. ASN Neuro. 2015 Sep-Oct; 7(5). 2. Febinger HY, Thomasy HE, Pavlova MN, Ringgold KM, Barf PR, George AM, Grillo JN, PubMed Bachstetter AD, Garcia JA, Cardona AE, Opp MR, Gemma C. Time-dependent effects of CX3CR1 in a mouse model of mild traumatic brain injury. J Neuroinflammation. 2015 Sep 02; 12:154. 3. Maphis N, Xu G, Kokiko-Cochran ON, Cardona AE, Ransohoff RM, Lamb BT, Bhaskar PubMed K. Loss of tau rescues inflammation-mediated neurodegeneration. Front Neurosci. 2015; 9:196. 4. Grigsby JG, Cardona SM, Pouw CE, Muniz A, Mendiola AS, Tsin AT, Allen DM, PubMed Cardona AE. The role of microglia in diabetic retinopathy. J Ophthalmol. 2014; 2014:705783. 5. Sandstrom RS, Foret MR, Grow DA, Haugen E, Rhodes CT, Cardona AE, Phelix CF, PubMed Wang Y, Berger MS, Lin CH. Epigenetic regulation by chromatin activation mark H3K4me3 in primate progenitor cells within adult neurogenic niche. Sci Rep. 2014 Jun 20; 4:5371. 6. Garcia JA, Cardona SM, Cardona AE. Isolation and analysis of mouse microglial cells. PubMed Curr Protoc Immunol. 2014 Feb 04; 104:Unit 14.35.. 7. Sosa RA, Murphey C, Ji N, Cardona AE, Forsthuber TG. The kinetics of myelin antigen PubMed uptake by myeloid cells in the central nervous system during experimental autoimmune encephalomyelitis. J Immunol. 2013 Dec 15; 191(12):5848-57. 8. Garcia JA, Pino PA, Mizutani M, Cardona SM, Charo IF, Ransohoff RM, Forsthuber PubMed TG, Cardona AE. Regulation of adaptive immunity by the fractalkine receptor during autoimmune inflammation. J Immunol. 2013 Aug 01; 191(3):1063-72. 9. Mishra PK, Morris EG, Garcia JA, Cardona AE, Teale JM. Increased accumulation of PubMed regulatory granulocytic myeloid cells in mannose receptor C type 1-deficient mice correlates with protection in a mouse model of neurocysticercosis. Infect Immun. 2013 Apr; 81(4):1052-63. 10. Cardona SM, Garcia JA, Cardona AE. The fine balance of chemokines during disease: PubMed trafficking, inflammation, and homeostasis. Methods Mol Biol. 2013; 1013:1-16. 11. Garcia JA, Cardona SM, Cardona AE. Analyses of microglia effector function using PubMed CX3CR1-GFP knock-in mice. Methods Mol Biol. 2013; 1041:307-17. 12. Mizutani M, Pino PA, Saederup N, Charo IF, Ransohoff RM, Cardona AE. The PubMed fractalkine receptor but not CCR2 is present on microglia from embryonic development throughout adulthood. J Immunol. 2012 Jan 01; 188(1):29-36. 13. Hamann I, Unterwalder N, Cardona AE, Meisel C, Zipp F, Ransohoff RM, Infante- PubMed Duarte C. Analyses of phenotypic and functional characteristics of CX3CR1expressing natural killer cells. Immunology. 2011 May; 133(1):62-73. 14. Pino PA, Cardona AE. Isolation of brain and spinal cord mononuclear cells using PubMed percoll gradients. J Vis Exp. 2011 Feb 02; (48). 15. Ransohoff RM, Cardona AE. The myeloid cells of the central nervous system PubMed parenchyma. Nature. 2010 Nov 11; 468(7321):253-62. 16. Saederup N, Cardona AE, Croft K, Mizutani M, Cotleur AC, Tsou CL, Ransohoff RM, PubMed Charo IF. Selective chemokine receptor usage by central nervous system myeloid cells in CCR2-red fluorescent protein knock-in mice. PLoS One. 2010 Oct 27; 5(10):e13693. 17. Lee S, Varvel NH, Konerth ME, Xu G, Cardona AE, Ransohoff RM, Lamb BT. CX3CR1 PubMed deficiency alters microglial activation and reduces beta-amyloid deposition in two Alzheimer's disease mouse models. Am J Pathol. 2010 Nov; 177(5):2549-62. 18. Cardona AE, Li M, Liu L, Savarin C, Ransohoff RM. Chemokines in and out of the PubMed central nervous system: much more than chemotaxis and inflammation. J Leukoc Biol. 2008 Sep; 84(3):587-94. 19. Cardona AE, Sasse ME, Liu L, Cardona SM, Mizutani M, Savarin C, Hu T, Ransohoff PubMed RM. Scavenging roles of chemokine receptors: chemokine receptor deficiency is associated with increased levels of ligand in circulation and tissues. Blood. 2008 Jul 15; 112(2):256-63. 20. Ransohoff RM, Liu L, Cardona AE. Chemokines and chemokine receptors: PubMed multipurpose players in neuroinflammation. Int Rev Neurobiol. 2007; 82:187-204. 21. Cardona AE, Pioro EP, Sasse ME, Kostenko V, Cardona SM, Dijkstra IM, Huang D, PubMed Kidd G, Dombrowski S, Dutta R, Lee JC, Cook DN, Jung S, Lira SA, Littman DR, Ransohoff RM. Control of microglial neurotoxicity by the fractalkine receptor. Nat Neurosci. 2006 Jul; 9(7):917-24. 22. Cardona AE, Huang D, Sasse ME, Ransohoff RM. Isolation of murine microglial cells PubMed for RNA analysis or flow cytometry. Nat Protoc. 2006; 1(4):1947-51. 23. Cardona AE, Gonzalez PA, Teale JM. CC chemokines mediate leukocyte trafficking PubMed into the central nervous system during murine neurocysticercosis: role of gamma delta T cells in amplification of the host immune response. Infect Immun. 2003 May; 71(5):2634-42. 24. Cardona AE, Teale JM. Gamma/delta T cell-deficient mice exhibit reduced disease PubMed severity and decreased inflammatory response in the brain in murine neurocysticercosis. J Immunol. 2002 Sep 15; 169(6):3163-71. 25. Melby PC, Tabares A, Restrepo BI, Cardona AE, McGuff HS, Teale JM. Leishmania PubMed donovani: evolution and architecture of the splenic cellular immune response related to control of infection. Exp Parasitol. 2001 Sep; 99(1):17-25. 26. Cardona AE, Restrepo BI, Jaramillo JM, Teale JM. Development of an animal model PubMed for neurocysticercosis: immune response in the central nervous system is characterized by a predominance of gamma delta T cells. J Immunol. 1999 Jan 15; 162(2):995-1002. 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