Catherine Tsilfidis, Ph. D. General Campus (see Contact page for maps)

Project title: Regeneration in the newt, Notophthalmus viridescens.
Amphibians such as the newt, Notophthalmus viridescens, have a unique ability to regenerate arms legs, spinal cord, eye structures and many vital organs. Through a process called epimorphic regeneration, structures lost to injury or amputation are replaced, such that the regenerated structure is indistinguishable from the original. An understanding of the basic mechanisms involved in these processes will not only advance our fundamental knowledge of the biology of regeneration, but will also have considerable clinical implications for humans. The most critical stage in the regeneration response, and the reason why some amphibians possess the ability to regenerate, is their ability to induce the tissues at the site of injury to revert to an embryonic-like state - a process called dedifferentiation. An understanding of the molecular mechanisms involved in dedifferentiation is essential in order to enhance the regenerative ability in non-regenerating animals. One of the major research aims of my laboratory is to identify factors controlling the onset of dedifferentiation so that we may use these factors to improve regenerative potential in man.

Project title: Gene and stem cell therapy in animal models of retinal degeneration
Inherited retinal degenerations lead to a progressive loss of vision. Most often, they are characterized by a gradual loss of the photoreceptors in the retina. Cell death occurs through the process of apoptosis. Research in our laboratory is aimed at preventing the photoreceptor loss which is associated with diseases such as retinitis pigmentosa (RP). We believe that regardless of the genetic mutation which a cell possesses, if we can target and prevent the ultimate death of the cell, we will be able to retain function in the photoreceptors and prevent vision loss. We are using XIAP (the X-linked inhibitor of apoptosis protein), a potent inhibitor of cell death. It prevents apoptosis by blocking the action of caspases, which are enzymes that are involved in the cell death pathway. Virus containing XIAP is injected into the eye in the sub-retinal space, and infects photoreceptor cells with high efficiency. We have used this approach to show that XIAP protects photoreceptors in animal models of retinal ischemia (stroke) and retinitis pigmentosa. These results hold tremendous promise for the treatment of human retinitis pigmentosa. We are also interested in studying the ability of adult stem cells to repair damage caused by retinal ischemia or photoreceptor degeneration. We will deliver stem cells into the damaged eye and monitor cell survival, migration and integration. We will determine whether the introduced stem cells migrate to the correct layers of the retina, make the correct connections and acquire the characteristics of neighbouring cells. These studies will have potential applications in retinitis pigmentosa, glaucoma and retinal ischemia in humans.