Research in my lab focuses on both eye development and disease. For many years we have been studying one of the central problems in developmental biology: how tissues and organs become directed and committed to their particular fates. Most of our research has focused on formation of the embryonic eye, which has a long history of study and where many molecular and genetic tools allow access to study this fascinating process, in addition to our interest in the development of vision in general. Much of our research uses the amphibian Xenopus because one can obtain large numbers of embryos to study that can be raised easily and manipulated surgically to understand how interactions of tissues in the embryo lead to eye formation. While we are all interested in mammalian development, it is much more difficult to study mammalian embryonic development and, interestingly, the processes that lead to eye formation are highly conserved between frog and human, and thus studies in the frog “model” system have important applications for human biology. In addition, we have developed gene editing tools for Xenopus allowing us to make mutations in key regulatory genes to understand the genetic basis for eye formation.
Our research on Xenopus is complemented by an interest in human congenital eye diseases. We are working with patients who have congenital eye diseases that in many ways mirror what we see in our frog embryos: genes necessary for normal eye development are often the ones disrupted in congenital eye diseases, since the latter are fundamentally due to disruption of embryonic processes. So what we learn with our frogs applies to humans and vice versa. For example, mutations in the very important gene PAX6 cause serious disruption of eye formation in humans, resulting in diminished vision, serious damage to the cornea, and glaucoma. We have several studies underway examining the basis for disease phenotypes in these patients. The Pax6 gene is also essential for early eye development, and we have now made a frog mutant which has the same set of eye malformations seen in humans, and is thus valuable for both learning about development and disease.
Other genes we are studying affect processes like pigmentation in eye. Mutation of one such gene, which cause albinism in frogs, is also responsible for the Hermansky-Pudlak Syndrome in humans, which causes albinism and serious bleeding disorders. The hope is that by examining the frog mutation that we can learn more about how this particular gene is important in eye development, and elsewhere in the embryo, and, as a result, how to potentially work toward better treatments for patients.