A Conversation With Dr. Chen
2017-Present Assistant Professor, Ophthalmology, University of Pittsburgh School of Medicine
2011-2017 Postdoctoral Scholar, Labotory of Krzysztof Palczewski, Department of Pharmacology, Case Western Reserve University
Dr. Yuanyuan Chen obtained her Bachelor’s degree in Biological Sciences in Fudan University in Shanghai, China, and then she moved to the U.S. and pursued her Ph.D. in Biochemistry with Dr. Paul R. Carey at Case Western Reserve University from 2004-2010. She joined the vision research field when she worked with Dr. Krzysztof Palczewski in the Department of Pharmacology at Case Western Reserve University in 2011. Dr. Palczewski is a renowned biochemist in vision research who made significant contributions in revealing the molecular structure of the visual pigment rhodopsin, as well as in drug development in blinding disease.
Dr. Chen joined the Department of Ophthalmology at the University of Pittsburgh in 2017 as an assistant professor. Her 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. Dr. Chen holds two pending patents and published 18 research and review papers. She has been awarded the highly competitive K99/R00 path to Independence research award from National Eye Institute, and recently she received the Allen Humphrey, PhD Excellence in Mentoring Award and the Bruce and Barbara Wiegand Entreprenerial Research Award. Her research project on pharmacological studies of rhodopsin metabolism has received an R01 funding support from the National Eye Institute (2020-20250).
2004-2010 Case Western Reserve University, PhD in Biochemistry
1999-2003 Fudan University, BS in Biological Sciences
Education & Training
- 2004-2010 Case Western Reserve University, PhD in Biochemistry
- 1999-2003 Fudan University, BS in Biological Sciences
- 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: PMC4554260.
- 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.
Research Interest Summary
Abhishek Vats, PhD, Postdoctoral Associate, Ophthalmology
Yibo Xu, PhD, Postdoctoral Associate, Ophthalmology
Jinling Zhang, PhD, Postdoctoral Associate, Ophthalmology
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.
Chen lab website: https://ivy00chen.wixsite.com/chenlab
National Eye Institute (R00-EY024992): 08/01/17-06/30/20.
“Drug Discovery and Mechanistic Study of P23H Rhodopsin Associated Retinitis Pigmentosa”
Pending: NIH R01: Pharmacological studies of rhodopsin metabolism