Dr. Brooks studies a potentially blinding congenital malformation of the eye called uveal coloboma. The condition is caused by failure of the optic fissure to close during the fifth week of human gestation. Although the embryology leading to coloboma has been well-characterized for decades, less is known about the genetic and developmental processes responsible for this condition, making genetic counseling and molecular diagnosis difficult.
The Brooks laboratory integrates clinical and genetic data from uveal coloboma patients with molecular, developmental, and biochemical studies of normal and faulty optic fissure closure in model systems. The ultimate goal of the research is to apply knowledge from clinical and laboratory studies to molecular diagnosis in families with coloboma and to devise prevention and treatment strategies. Dr. Brooks applies Mendelian and complex genetics approaches to studying uveal coloboma in patients. His laboratory has identified a unique syndrome in which abnormal vertebral segmentation cosegregates with coloboma in an autosomal dominant fashion. He is leading efforts to define the clinical phenotypes of coloboma patients and their first-degree relatives. Through careful phenotyping with state-of-the art clinical tools, the Brooks laboratory is identifying potential clinical risk factors and microforms of coloboma.
Using a combination of laser-capture microdissection and gene expression analysis, Dr. Brooks has identified 221 genes that are differentially regulated at the closing edges of the optic fissure before, during, and after closure. He has discovered that two genes - Nlz1 and Nlz2 - are important in regulating closure via a Pax2-dependent mechanism; he is currently exploring how these genes interact with other transcriptional regulators of Pax2 during development. He is also studying the role these genes play in human disease and non-ocular phenotypes associated with disruption of either of these genes, and the developmental role of other differentially-related genes, including cell-signaling and cell-adhesion molecules.
Last Reviewed: October 31, 2010