Summary: The research in Dr. Hackam’s laboratory encompasses the fields of mammalian genetics and ophthalmology, using high-throughput genomics technologies and bioinformatics analyses to investigate molecular mechanisms underlying critical events in retinal development, degeneration and tumorigenesis.

Abigail S. Hackam, Ph.D.
Assistant Professor of Ophthalmology

View published research articles by this doctor in the National Library of Medicine.

Current Projects

The main topics of exploration in my laboratory are the analyses of genes and pathways involved in photoreceptor degeneration, cellular differentiation during retinal development, the molecular pathogenesis of ocular tumors, and the genetic basis of human retinal disease.

1. Identification of photoreceptor protective proteins: the role of the Wnt signaling pathway in retinal degeneration. The retina is a thin multi-layer tissue at the back of the eye that is essential for our view of the world. Degenerative diseases of the retina, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), lead to visual difficulties and eventual loss of sight. These diseases are a result of damage and death of the light-sensing cells in the retina, the photoreceptors. The treatment of retinal degeneration diseases requires a better understanding of the molecules involved in regulating photoreceptor survival. A major focus of my research is identifying and characterizing photoreceptor protective factors.

Microarray analyses of retinal degeneration suggest a role for the Wnt signaling pathway, a critical intercellular communication pathway. We are currently using animal models, primary retinal culture (Figure, left) and purified Muller glia cultures (Figure, right) to determine whether Wnt signaling molecules are neuroprotective in the degenerating retina.

2. Mechanisms of tumorigenesis in ocular cancer. In this study we are exploring whether manipulating the Wnt signaling pathway has potential as a novel therapeutic strategy for retinoblastoma, which is the most common primary intraocular eye cancer in children (Figure, R=retina, T=tumor). Because most cancer cells contain inactivating mutations in the Rb1 genes, we expect that our data on the intersection of Wnt and Rb1 pathways will be applicable to many other types of tumors.

3. Gene discovery in the developing retina. The chick embryo is a powerful model system for studying retinal development. We have used the chick embryo to identity candidate molecules involved in the development of photoreceptors and other retinal cell types. Using microarrays and in situ hybridization, we isolated retina-enriched genes that were differentially expressed during development, with specific focus on genes with possible roles in transcriptional regulation, apoptosis or intercellular signaling. Studies are planned to determine the involvement of these candidate genes in retinal development by a combination of gene transfer and RNA knock-down technologies.

Microarray identification of genes in the chick retina. Two genes retina-enriched genes that showed unique developmentally regulated temporal and spatial expression patterns in the chick. These genes may be important to the development of photoreceptors.

4. Identification of genetic pathways in retinal degeneration. We have used custom retinal microarrays to compare gene expression changes in retinal degenerations in various mutant rat and mouse disease models. A main interest is to determine at what point degenerations that occur at different rates, or are induced by different genetic mutations, converge along shared pathways towards apoptosis. These experiments will provide insight into mechanisms of cell death in the retina and could indicate whether general therapeutic intervention, rather than mutation-specific methodologies, would be effective.

5. Identification of mutated genes in human retinal disease. Microarray analysis of normal and degenerated retina and comprehensive bioinformatics analyses have identified a large number of photoreceptor-expressed genes that are localized within critical chromosomal regions for inherited retinal disease. These genes can be considered good candidates for involvement in retinal disease, and studies are being planned to collect blood samples from affected individuals for mutation screens of these genes.