Michael A Walter
Medicine & Dentistry-Medical Genetics
University of Alberta
Summary of research:
My laboratory focuses on studying the basis of inherited human malformations that cause glaucoma. We identified forkhead C1 (FOXC1) as a cause of Axenfeld-Rieger Syndrome (ARS). We have determined how FOXC1 mutations affect protein function. We combined our biochemical and cell biology data with molecular modeling to yield insight into the molecular events underlying FOXC1 functional deficits. We have isolated genes regulated by FOXC1; implicating the fibroblast growth factor and oxidative stress response pathways in ocular maldevelopment and glaucoma.. We have shown that quantitative differences PITX2 activity are the basis of the AR phenotype spectrum. Like FOXC1, PITX2 is a transcription factor mutations of which also cause ARS and glaucoma. Our studies have revealed a link between PITX2 and FOXC1, hinting at a common transcriptional role for both genes. We have recently found that glaucoma-associated variations of WDR36 cause functional defects only when combined with mutations of a second gene, e.g., STI1. This work indicates that WDR36 is involved in polygenetic forms of glaucoma, and implicates, for the first time, rRNA processing and chaparonin pathways in glaucoma.