Dr. Chen's research interests are focused on the molecular mechanism of photoreceptor cell death in retinal diseases, as well as pharmacological treatments of such blinding diseases. She sets up a research lab that holds the platforms for biochemical, cell and retinal culture as well as in-vivo studies of photoreceptor cell morphology and function in rodent models of retinal degeneration.
Protein misfolding is commonly seen in inherited retinal degeneration such as Leber congenital amaurosis, Stargardt disease or retinitis pigmentosa. Genetic mutation of one nucleotide often leads to the change of one amino acid in the encoded protein that may disrupt the amino acid interactions essential for stabilizing the native folding of the protein. Unfortunately, most inherited retinal degenerations currently lack effective treatments.
Even though gene therapy has brought new hope to the treatment of inherited retinal degenerations, pharmacological treatment is still favored because small molecule drugs are easy for manufacture and storage, easy to be taken orally or topically, and are easy to withdraw in case of adverse effects. Specifically, we are focusing on understanding the disease mechanism and drug discovery of retinitis pigmentosa associated with mutations in the gene encoding the visual pigment, rhodopsin. Targeting the early events that cumulatively lead to retinal degeneration, we have identified novel small molecules that restore the homeostasis of rhodopsin mutants. We are studying the mechanism of actions of the most effective and potent compounds, characterizing their metabolism and effects in a mouse model expressing a rhodopsin mutant, to develop an efficacious and safe treatment regimen that can be further tested in large animals and clinical trials. Additionally, we are trying to test the retinal protective agents discovered from the rhodopsin misfolding model to other retinal degeneration models, such as light-damage