The long-term objective of this project is to understand how age-related changes in the lens proteins contribute to cataract. The proposed research will examine the composition and structure of light scattering protein aggregates and water-insoluble protein that form in aged human lenses using mass spectrometry.
The specific aims of the project are to: 1) quantify the protein composition of protein aggregates and water-insoluble protein in normal and cataractous human lenses;2) identify sites in aggregated and water-insoluble lens proteins that form intermolecular disulfide cross-links during aging, and 3) map the contact sites occurring in aggregated and water-insoluble lens proteins using chemical cross-linkers. The results will provide new information about the structure of light scattering proteins in human lens so that the mechanism of age-related protein aggregation and insolubilization can be eventually deduced. This information may lead to therapeutic strategies to slow the rate of age-related cataract formation by inhibiting protein aggregation. The research is important to human health, because cataracts are a major human disease for which there is no useful treatment other than surgical extraction of the lens.
Age-related cataracts are a major health problem caused by aggregation and light scatter of lens proteins. This study will use mass spectrometry to analyze the composition and structure of protein aggregates in human lens. The results may suggest therapies to slow cataract formation by inhibiting protein aggregation in the aged lens.
|Shang, Fu; Wilmarth, Phillip A; Chang, Min-lee et al. (2014) Newborn mouse lens proteome and its alteration by lysine 6 mutant ubiquitin. J Proteome Res 13:1177-89|
|Avenarius, Matthew R; Saylor, Katherine W; Lundeberg, Megan R et al. (2014) Correlation of actin crosslinker and capper expression levels with stereocilia growth phases. Mol Cell Proteomics 13:606-20|
|Krey, Jocelyn F; Wilmarth, Phillip A; Shin, Jung-Bum et al. (2014) Accurate label-free protein quantitation with high- and low-resolution mass spectrometers. J Proteome Res 13:1034-44|
|Lampi, Kirsten J; Wilmarth, Phillip A; Murray, Matthew R et al. (2014) Lens ?-crystallins: the role of deamidation and related modifications in aging and cataract. Prog Biophys Mol Biol 115:21-31|
|Nili, Mahta; David, Larry; Elferich, Johannes et al. (2013) Proteomic analysis and molecular modelling characterize the iron-regulatory protein haemojuvelin/repulsive guidance molecule c. Biochem J 452:87-95|
|Grey, Angus C; Walker, Kerry L; Petrova, Rosica S et al. (2013) Verification and spatial localization of aquaporin-5 in the ocular lens. Exp Eye Res 108:94-102|
|Giblin, Frank J; David, Larry L; Wilmarth, Phillip A et al. (2013) Shotgun proteomic analysis of S-thiolation sites of guinea pig lens nuclear crystallins following oxidative stress in vivo. Mol Vis 19:267-80|
|Wang, Zhen; Han, Jun; David, Larry L et al. (2013) Proteomics and phosphoproteomics analysis of human lens fiber cell membranes. Invest Ophthalmol Vis Sci 54:1135-43|
|Shin, Jung-Bum; Krey, Jocelyn F; Hassan, Ahmed et al. (2013) Molecular architecture of the chick vestibular hair bundle. Nat Neurosci 16:365-74|
|Spinelli, Kateri J; Klimek, John E; Wilmarth, Phillip A et al. (2012) Distinct energy metabolism of auditory and vestibular sensory epithelia revealed by quantitative mass spectrometry using MS2 intensity. Proc Natl Acad Sci U S A 109:E268-77|
Showing the most recent 10 out of 17 publications