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My research focuses on mapping the principal signals involved in regulating cell differentiation and tissue development, particularly those activated downstream of the classical cell adhesion molecules, integrins and cadherins. We investigate how these pathways guide a cell to reach its full differentiated potential. For the activation of these pathways to elicit their normal function in a cell and not tip the balance to a disease state, or even cell death, they must be highly regulated. We also examine the mechanisms that regulate these differentiation-inducing pathways and how aberrations in these pathways lead to disease. The system we use for the majority of our studies is the embryonic lens. The embryonic lens is a unique developmental paradigm that lends itself well to investigations of the role of cell adhesion and signaling molecules in differentiation and development. We use a combination of biochemical and imaging approaches to analyze the differentiation-state specific assembly and activation of signaling complexes in the embryonic lens. This approach makes it possible to map the dynamic changes in adhesion-dependent signaling pathways that occur in vivo. Our studies of the mechanism of lens development and disease have been enhanced by our development of culture systems that mimic lens differentiation, the lens disease Cataract and the major complication of cataract surgery, Posterior Capsular Opacification (PCO). With these systems we can perturb specific signaling pathways through either an siRNA approach or the use of pharmaceutical inhibitors.
The system we use for the majority of our studies is the embryonic lens. The embryonic lens is a unique developmental paradigm that lends itself well to investigations of the role of cell adhesion and signaling molecules in differentiation and development. We use a combination of biochemical and imaging approaches to analyze the differentiation-state specific assembly and activation of signaling complexes in the embryonic lens. This approach makes it possible to map the dynamic changes in adhesion-dependent signaling pathways that occur in vivo. Our studies of the mechanism of lens development and disease have been enhanced by our development of culture systems that mimic lens differentiation, the lens disease Cataract and the major complication of cataract surgery, Posterior Capsular Opacification (PCO). With these systems we can perturb specific signaling pathways through either an siRNA approach or the use of pharmaceutical inhibitors.
We hope our studies will lead to better understanding of how cells attain their differentiated phenotype and aid in the prevention of congenital diseases. Through our identification of signaling pathways responsible for the induction of cataract and PCO we hope to develop pharmaceutical strategies to prevent these eye diseases, as well as diseases in other tissues that develop through similar mechanisms.
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