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.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
7K01RR017626-04
Application #
7235840
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Program Officer
Watson, William T
Project Start
2003-09-30
Project End
2008-07-31
Budget Start
2006-08-01
Budget End
2007-07-31
Support Year
4
Fiscal Year
2006
Total Cost
$120,096
Indirect Cost
Name
Ohio State University
Department
Veterinary Sciences
Type
Schools of Veterinary Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
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