Ph.D. Microbiology & Immunology. 1992.
B.S. Microbiology & Immunology.
The goal of our research is to understand the roles of cell signaling pathways and transcriptional networks in eye development and how disruptions in these processes lead to vision loss and eye disease. We are particularly interested in identifying the mechanisms by which developmental defects contribute to glaucoma, which causes irreversible vision loss. Our current focus is the homeodomain transcription factor PITX2, which when mutated in humans results in ocular anterior segment dysgenesis ( defects in the cornea, iris, and structures within the iridocorneal angle) and a high risk for glaucoma. We are applying a variety of approaches, including mouse genetics, functional genomics, biochemistry, and cell culture to determine the mechanisms by which PITX2 regulates development of anterior segment structures. We have discovered that a major role for PITX2 during development of the anterior segment is to regulate cell signaling. We are currently seeking to understand how PITX2 does this and what additional functions PITX2 has during eye development. A longer-term goal will be to understand how defects in these structures leads to optic nerve defects and glaucoma. The ultimate aim of our research program is that knowledge gained may eventually contribute to new diagnostic tests or the design of rational treatment strategies for blinding eye diseases such as glaucoma.
A. L. Zacharias, M. Lewandoski, M. A. Rudnicki, and Gage P. J. 2011. Pitx2 is an upstream activator of extraocular myogenesis and survival. Developmental Biology 349:395-405. PMCID3019256
Zacharias A. L. and Gage P. J. 2010. Canonical Wnt/ïÅ¢-catenin signaling is required for maintenance but not activation of Pitx2 expression in neural crest during eye development. Developmental Dynamics 239:3215-25. PMCID3073314.
E. A. Bassett, T. Williams, A. L. Zacharias, P. J. Gage, S. Fuhrmann, and J. A. West-Mays. 2010. AP-2a knockout mice exhibit optic cup patterning defects and failure of optic stalk morphogenesis. Human Molecular Genetics 19:1791-804. PMCID2850623.
Acharya, D. J. Lingenfelter, L. Huang, P. J. Gage, and M A. Walter. 2009. Human PRKC apoptosis WT1 regulator is a novel PITX2-interacting protein that regulates PITX2 transcriptional activity in ocular cells. J. Bio. Chem. 284:34829-38. PMCID2787345.
P. J. Gage, M. Qian, D. Wu, and K. I. Rosenberg. 2008. The canonical Wnt signaling antagonist DKK2 is an essential effector of PITX2 function during eye development. Developmental Biology. 317:310-24. PMCID2387126.