Current Research
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 trial
Selected Recent Publications
Feng B, Liu X, Chen Y. A Rhodopsin Transport Assay by High-Content Imaging Analysis. J Vis Exp. 2019 Jan 16;(143). doi: 10.3791/58703. PubMed PMID: 30735172; PubMed Central PMCID: PMC6518421.
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. doi: 10.1038/s41467-018-04261-1. PubMed PMID: 29773803; PubMed Central PMCID: PMC5958115. * Corresponding authors.
Chen Y, Brooks MJ, Gieser L, Swaroop A, Palczewski K. Transcriptome profiling of NIH3T3 cell lines expressing opsin and the P23H opsin mutant identifies candidate drugs for the treatment of retinitis pigmentosa. Pharmacol Res. 2016;115:1-13. PubMed PMID: 27838510.
Jastrzebska B, Chen Y, Orban T, Jin H, Hofmann L, Palczewski K. Disruption of Rhodopsin Dimerization with Synthetic Peptides Targeting an Interaction Interface. J Biol Chem. 2015;290(42):25728-44. PubMed PMID: 26330551 PMCID: PMC4646215.
Chen Y, Tang H, Seibel W, Papoian R, Li X, Lambert NA, Palczewski K. A High-Throughput Drug Screening Strategy for Detecting Rhodopsin P23H Mutant Rescue and Degradation. Invest Ophthalmol Vis Sci. 2015;56(4):2553-67. PubMed PMID: 25783607 PMCID: PMC455260.
Chen Y, Tang H, Seibel W, Papoian R, Oh K, Li X, Zhang J, Golczak M, Palczewski K, Kiser PD. Identification and characterization of novel inhibitors of Mammalian aspartyl aminopeptidase. Mol Pharmacol. 2014;86(2):231-42. PubMed PMID: 24913940 PMCID: PMC4127928.