Overview
Initiation of air breathing at birth is dependent upon an highly orchestrated developmental program leading to the formation of an extensive gas exchange surface (air-blood barrier). Genetic mutations and environmental insults that disrupt the structure of the air-blood barrier can lead to death shortly after birth or life-long lung disease. Cytoprotective pathways involved in adaptation to genetic and environmental stresses play a critical role in preventing or slowing the progression of chronic lung disease and may provide novel targets for therapeutic intervention. Dr. Weaver's lab is currently studying two important pathways involved in protection of the epithelial surface of the air-blood barrier:
- ERAD involves the selective recognition and rapid elimination of misfolded proteins (arising from inherited or spontaneous mutations) to prevent epithelial cell injury and death.
- Antimicrobial peptides recognize and promote clearance of inhaled microorganisms to prevent colonization of the airspaces and injury to epithelial cells.
Related Publications
Bridges JP, Xu Y, Na CL, Wong HR, and Weaver TE. Adaptation and increased susceptibility to infection associated with constitutive expression of misfolded SP-C. J Cell Biol 172: 395-407, 2006.
Serrano, AG, Ryan, M, Weaver, TE and Pérez-Gil, J: Critical structure-function determinants within the N-terminal region of Pulmonary Surfactant Protein SP-B. Biophysical Journal, in press.
Ikegami, M, Whitsett, JA, Martis, PC and Weaver, TE: Reversibility of lung inflammation caused by SP-B deficiency. American Journal of Physiology: Lung Cell and Molecular Physiology, in press.
Ryan, MA, Akinbi, HT, Serrano, AG, Perez-Gil, J, Wu, H, McCormack, FX and Weaver, TE: Antimicrobial activity of native and synthetic surfactant protein B peptides. Journal of Immunology, in press.
Nesslein, LL, Melton, KR, Ikegami, M, Na, C-L, Wert, SE, Rice, WR, Whitsett, JA and Weaver, TE: Partial SP-B deficiency perturbs lung function and causes air space abnormalities. American Journal of Physiology: Lung Cell and Molecular Physiology 288:1154-1161, 2005.
Ryan, MA, Qi, X, Serrano, AG, Ikegami, M, Perez-Gil, J, Johansson, J and Weaver, TE: Mapping and analysis of the lytic and fusogenic domains of surfactant protein B. Biochemistry 44:861-872, 2005.
Markart, P, Faust, N, Graf, T, Na, C-L, Weaver, TE and Akinbi, HT: Comparison of the microbicidal and muramidase activities of mouse lysozyme M and P. Biochemical Journal 380:385-392, 2004.
Li, J, Hosia, W, Hamvas, A, Thyberg, J, Jörnvall, H, Weaver, TE and Johansson, J: The N-terminal propeptide of lung surfactant protein C is necessary for biosynthesis and prevents unfolding of a metastable ?-helix. Journal of Molecular Biology 338:857-862, 2004.
Ueno, T, Linder, S, Na, C-L, Rice, WR, Johansson, J and Weaver, TE: Processing of pulmonary surfactant protein B by napsin and cathepsin H. Journal of Biological Chemistry 279:16178-16184, 2004.
Li, J, Ikegami, M, Na, C-L, Hamvas, A, Espinassous, Q, Chaby, R, Nogee, LM, Weaver, TE and Johansson, J: N-terminally extended surfactant protein (SP) C isolated from SP-B-deficient children has reduced surface activity and inhibited lipopolysaccharide binding. Biochemistry 43:3891-3898, 2004.
Markart, P, Korfhagen, TR, Weaver, TE and Akinbi, HT: Mouse lysozyme M is important in pulmonary host defense against Klebsiella pneumoniae infection. American Journal of Respiratory and Critical Care Medicine 169:454-458, 2004.
Timothy E. Weaver MS, PhD
Division of Pulmonary Biology
Children's Hospital Research Foundation
3333 Burnet Avenue
Cincinnati, OH 45229-3039
Email: tim.weaver@cchmc.org
Phone: 513-636-7223
Fax: 513-636-7868
Secretary: 513-636-4830
