Yuanyuan Chen, Ph.D.
- Retinal degeneration
- Drug discovery
- Retinal imaging and physiology
- Rhodopsin biochemistry
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 modify dosage and frequency of drug administration. Specifically, we are focusing on understanding the disease mechanism and drug discovery of retinitis pigmentosa associated with mutations in the gene encoding the dim-light receptor protein, 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 blinding disease models, such as congenital stationary night blindness.
Select Recent Publications
Chen Y*, Chen Y, Jastrzebska B, Golczak M, Gulati S, Tang H, Seibel W, Li X, Jin H, Han Y, Gao S, Zhang J, Liu X, Heidari-Torkabadi H, Stewart PL, Harte WE, Tochtrop GP, Palczewski K*. A novel small molecule chaperone of rod opsin and its potential therapy for retinal degeneration. Nat Commun. 2018 May 17;9(1):1976.
Feng, B., Liu, X., Chen, Y. A Rhodopsin Transport Assay by High-Content Imaging Analysis. J. Vis. Exp. 2019 Jan 143, e58703, doi:10.3791/58703.
All publications are found here: https://www.ncbi.nlm.nih.gov/myncbi/yuanyuan.chen.3/bibliography/public/
Research Grants: NEI R00EY024992 and Start-up fund
Yuanyuan Chen, Ph.D.
Department of Ophthalmology,
Department of Pharmacology and Chemical Biology,
McGowan Institute of Regenerative Medicine,
University of Pittsburgh,
3501 Fifth Avenue,
Pittsburgh, PA 15213