CANDIDATE: I graduated from the University of Bristol in 1992, with Honours in Anatomical Science and Veterinary Science. At UAB I received training in laboratory animal medicine, laboratory animal pathology, and viral pathogenesis in animal models (Ph.D. February 2000; mentor Dr. Patricia Fultz). Subsequently, I elected to join Dr. Matalon's research group, where I might build on my knowledge of viral pathogenesis by cross-mining in electrophysiology, and apply these techniques to study the pathogenesis of human respiratory viral pneumonitides. RESEARCH: Respiratory syncytial virus (RSV) is commonest cause of lower respiratory tract disease in children worldwide. Pathogenesis of RSV-induced bronchiolitis is poorly understood, and effects of RSV infection on ion transport (a seminal function of respiratory epithelial cells) have not been investigated. I hypothesize that RSV infection of respiratory epithelial cells reduces their Na ? transport capacity. Preliminary studies have demonstrated that this hypothesis is correct, both in vitro and in RSV-infeeted BALB/c mice.
My aims for years 01- 03 are to: (1) quantify alterations in Na + transport across airway and alveolar epithelia in vivo and ex vivo, after infection of BALB/c mice with RSV; (2) define changes in Na + currents and amiloride-sensitive channel activity after RSV infection of murine epithelial cells in vitro; and (3) correlate alterations in Na + transport induced by RSV in vitro and in vivo with alterations in ENaC expression by marine respiratory epithelia. My plan for years 04-05 is to determine the role of the ubiquitin/proteasome pathway in mediating reduced Na+ transport after RSV infection of respiratory epithelia, and to identify the role of the RSV small hydrophobic (SH) gene product in modulation of Na + transport. I will use a combined electrophysiologic and biochemical approach to investigate effects of RSV on Na + transport at all levels, from the single cell to the whole animal, and to correlate these effects to Na + channel expression and degradation. My project will emphasize cross-training in diverse techniques, including short-circuit measurements across monolayers, radioisotopic ion flux studies, whole cell and single channel patch-clamp, and measurement of alveolar fluid clearance and nasal potential difference in mice. ENVIRONMENT: This SERCA, with Dr. Matalon (lung physiology) as mentor and Dr. Sullender (respiratory syncytial virus) as co-mentor, will provide the training and setting I require for my maturation into an independent scientist focused on comparative pathophysiologic effects of respiratory viruses on normal epithelial cell function.
| Hinzey, Adam; Alexander, Jacob; Corry, Jacqueline et al. (2011) Respiratory syncytial virus represses glucocorticoid receptor-mediated gene activation. Endocrinology 152:483-94 |
| Chen, Lan; Song, Weifeng; Davis, Ian C et al. (2009) Inhibition of Na+ transport in lung epithelial cells by respiratory syncytial virus infection. Am J Respir Cell Mol Biol 40:588-600 |
| Yu, Erin N Z; Traylor, Zachary P; Davis, Ian C (2009) Effect of ventilation pressure on alveolar fluid clearance and beta-agonist responses in mice. Am J Physiol Lung Cell Mol Physiol 297:L785-93 |
| Wolk, Kendra E; Lazarowski, Eduardo R; Traylor, Zachary P et al. (2008) Influenza A virus inhibits alveolar fluid clearance in BALB/c mice. Am J Respir Crit Care Med 178:969-76 |
| Davis, Ian C; Matalon, Sadis (2007) Epithelial sodium channels in the adult lung--important modulators of pulmonary health and disease. Adv Exp Med Biol 618:127-40 |
| Davis, Ian C; Lazarowski, Eduardo R; Chen, Fu-Ping et al. (2007) Post-infection A77-1726 blocks pathophysiologic sequelae of respiratory syncytial virus infection. Am J Respir Cell Mol Biol 37:379-86 |
| Davis, Ian C; Xu, Anna; Gao, Zhiqian et al. (2007) Respiratory syncytial virus induces insensitivity to beta-adrenergic agonists in mouse lung epithelium in vivo. Am J Physiol Lung Cell Mol Physiol 293:L281-9 |
| Hickman-Davis, Judy M; McNicholas-Bevensee, Carmel; Davis, Ian C et al. (2006) Reactive species mediate inhibition of alveolar type II sodium transport during mycoplasma infection. Am J Respir Crit Care Med 173:334-44 |
| Davis, Ian C; Lazarowski, Eduardo R; Hickman-Davis, Judy M et al. (2006) Leflunomide prevents alveolar fluid clearance inhibition by respiratory syncytial virus. Am J Respir Crit Care Med 173:673-82 |
| Davis, Ian C; Sullender, Wayne M; Hickman-Davis, Judy M et al. (2004) Nucleotide-mediated inhibition of alveolar fluid clearance in BALB/c mice after respiratory syncytial virus infection. Am J Physiol Lung Cell Mol Physiol 286:L112-20 |
