2006 Beckman Award Winners

Vivek Desai

Vivek Desai

CD44 and Posterior Capsular Opacification

Vivek D. Desai and Melinda K. Duncan
Department of Biological Sciences

Posterior capsular opacification (PCO) is an undesirable wound healing response in which the residual lens cells remaining in the eye after cataract surgery proliferate, migrate into the visual field, and synthesize extracellular matrix molecular similar to those found in scar tissue, damaging the patient's vision. PCO arises from epithelial mesenchymal transition (EMT) of lens epithelial cells. In other systems, CD44, a receptor for hyaluronan, has been identified to mediate changes in cellular proliferation, migration and cell identity leading to EMT. We hypothesize that the exposure of lens cells to hyaluronan based viscoelastics stimulates PCO following extracapsular lens extraction and that the hyaluronan receptor CD44 is involved in EMT of lens cells. In the adult mouse lens, CD44 is expressed in the lens fiber cells and not expressed in the lens epithelial cells, whereas in embryonic mouse lens, CD44 is not expressed in both the lens fiber cells and the lens epithelial cells. RT-PCR demonstrated that the "canonical" version of CD44 is the major CD44 splice variant in the lens. In adult mice, CD44 is not expressed in the lens epithelial cells immediately after the cataract surgery, however, its expression highly up-regulates in the lens epithelial cells 1-day following the surgery. Because of the dynamics of CD44 during the development of mouse lens and following the cataract surgery in adult mouse lens, out immediate future work is to study the distribution of CD44 ligands like hyaluronan and osteopontin.

Patrick Knerr

Patrick Knerr

Metal-triggered Hydrogelation of Designed β-hairpin Peptides

Patrick J. Knerr, Christopher Micklitsch, Colin Thorpe, and Joel P. Schneider
Department of Chemistry and Biochemistry

Peptides have been designed which undergo intramolecular folding from random coil to β-hairpin conformation, triggered by specific environmental conditions. The folded, amphiphilic β-hairpins then self-assemble to form an interlaced fibrillar network, converting the material from a liquid to a self-supporting, rigid hydrogel. Such responsive materials show great promise in tissue engineering, serving as scaffolds which mimic the extracellular matrix by allowing cellular adhesion and proliferation. Past work has demonstrated that pH, temperature, ionic strength and light can be utilized to stimulate the folding event. We are currently interested in developing a new trigger: metal-induced hydrogelation. Unnatural, multidentate α-amino acids have been synthesized to chelate strongly to divalent metal ions, most notably calcium or zinc. These ligands are subsequently incorporated into the primary sequence of a 20 residue peptide composed of two strand regions connected through a four residue type II' β-turn. This affords peptides in which folding and self-assembly is prevented at physiological conditions in the absence of the metal ion, but triggered when the ion is present.