Thomas Shearer

Ph.D., Biochemistry, University of Wisconsin, 1969
Associate Dean for Research, School of Dentistry, OHSU
Professor, Oral Molecular Biology, School of Dentistry
Professor, Department of Ophthalmology
Professor, Biochemistry and Molecular Biology

Adjunct Professor, Cell and Developmental Biology

Biochemistry of cataract formation; calpain proteolytic enzyme. Studies are being conducted on normal lens metabolism and the biochemistry of cataract formation. Opaque cataracts in the lens are the third leading cause of blindness in the United States. However, no one knows the biochemical reasons why most cataracts form. Once the biochemical basis is understood, nonsurgical therapies for cataract prevention and treatment can be developed. Our research program is investigating the changes in the proteins in the lens during cataract formation and determining the role of enzymes (especially calcium activated neutral protease) in the process. Techniques such as HPLC, SDS-PAGE, immuno blotting, tryptic mapping, protein sequencing, RT-PCR, and Northern blotting, microarray DNA analysis, protein overexpression are utilized. A convenient animal model (selenite-overdose cataract) is being utilized. A major focus is also currently testing the role of calpain proteolytic enzyme in experimental cataract. Our hypothesis is that selenite damages epithelial cells by oxidizing critical sulfhydryl groups in either calcium channels or on Ca-ATPase. Because of this, calcium accumulates in the lens and activates the proteolytic enzyme, calpain. Soluble b-crystallins are hydrolyzed by calpain. Partially proteolyzed crystallins no longer interact normally with other crystallins and they become insoluble, causing part of the light scatter. We recently discovered a lens specific calpain, Lp82, found in young rodent lenses, and this enzyme is responsible for much of the proteolysis in selenite cataract.

Ma H, Fukiage C, Kim YH, Duncan MK, Reed NA, Shih M, Azuma M, and Shearer TR. Characterization and expression of calpain 10 : a novel ubiquitous calpain with nuclear localization. J Biol Chem, published May 25, 2001 as 10.1074/jbc.M100603200 (online).

Ma H, Shih M, Fukiage C, Azuma M, Duncan MK, Reed NA, Richard I, Beckmann JS, Shearer TR. Influence of specific regions in Lp82 calpain on protein stability, activity, and localization within lens. Invest Ophthalmol Vis Sci. 2000 41(13):4232-9.

Shearer, T.R., Hong, M., Fukiage, C., and Azuma, M. Selenite cataract: review of the model., Molecular Vision 1997; 3: 8 http://www.emory.edu/molvis/v3/shearer

To contact Dr. Shearer directly: shearert@ohsu.edu