Abigail S. Hackam, Ph.D.
Cellular Mechanisms of Retinal Development, Degeneration and Tumorigenesis
Retinal Degeneration, Macular Degeneration, Retinoblastoma
The research in Dr. Hackam’s laboratory encompasses the fields of molecular genetics and ophthalmology. Our focus is on understanding cellular signaling pathways that contribute to retinal degenerations, dry eye and optic nerve damage. The overall goal is to generate new insights into the molecular basis of these ocular diseases in order to develop effective treatments.
Current research topics in the Hackam laboratory include the role of innate immunity in retinal degenerations, the Wnt signaling pathway in optic nerve regeneration and photoreceptor survival, the role of pollutants and air quality on dry eye and characterizing potential biomarkers in tears.
1. Identification of photoreceptor protective proteins: the role of the Wnt signaling pathways in retinal degeneration.
The retina is a thin multi-layer tissue at the back of the eye that is essential for vision. Degenerative diseases of the retina, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), lead to visual disturbances and eventual loss of sight. These diseases are a result of damage and death of photoreceptors, the light-sensing cells in the retina. The treatment of retinal degeneration diseases requires a better understanding of molecules involved in regulating photoreceptor survival. A major focus of our research is identifying and characterizing photoreceptor protective factors. Our studies explore the canonical and non-canonical Wnt signaling pathways, a critical intercellular communication pathway, which we showed protects photoreceptors from degeneration. Our current focus is on understanding the mechanisms of action of Wnt signaling, the receptors involved, the central role of Muller glia in inducing Wnt signaling, and the potential for Wnt activators as novel therapeutics for retinal disease.
2. The role of innate immunity in retinal degeneration.
We demonstrated that activation of various innate immunity pathways influences photoreceptor survival. Current topics include exploring mechanisms by which innate immunity signals suppress neuroprotective Wnt signaling, identifying glial-secreted cytokines that regulate anti- and pro-inflammatory signaling, characterizing the role of innate immunity receptors in neuronal cells, and determining how innate immune pathways are regulated by oxidative stress levels. Experimental approaches include proteomics, bioinformatics, in vivo and in vitro models, biochemical, cellular and molecular biology techniques. These studies provide insight into how inflammation and neuroprotective signaling are regulated during retinal degeneration.
3. Identification of optic nerve regeneration factors.
A major focus of the lab is repurposing embryonic axonal growth proteins to promote axonal regeneration after optic nerve injury. We demonstrated that various Wnt ligands and cytokines promote robust axonal growth and retinal ganglion cell survival. Our current work characterizes mechanisms of action, the roles of extrinsic and intrinsic regenerative cues, identifies the key receptors and signaling proteins involved, and tests virally delivered axonal growth factors. These experiments will ultimately identify potential therapeutic molecules for regrowing the optic nerve.
4. Biomarker analysis of dry eye.
This is a clinical project that characterizes the effect of specific features of the microenvironment on the ocular surface. Our research investigates levels of cytokines and growth factors in tears that could predict pain and progression of dry eye symptoms in patients.
5. Drug discovery.
We have developed a Muller glia-photoreceptor culture system that enables us to test novel compounds that regulate photoreceptor survival.