Yuanyuan Chen, PhD

Dr. Yuanyuan Chen is an Assistant Professor, Department of Ophthalmology, University of Pittsburgh. Dr. Chen received her BS in Biological Sciences at Fudan University, Shanghai, China.  At Case Western, she obtained her PhD in Biochemistry and was a postdoctoral scholar in pharmacology.  In 2015, she received an NEI K99/R00 Pathway to Independence Award (K99EY024992), “Drug discovery and mechanistic study of P23H rhodopsin associated retinitis pigmentosa,” as well being named an Outstanding Postdoctoral Fellow of Department of Pharmacology at Case Western University. She received an R01 grant in 2020 (R01EY030991), “Pharmacological studies of rhodopsin metabolism”. Dr. Chen is a member of the Association for Research in Vision and Ophthalmology (ARVO).  She serves as a journal reviewer for the following peer-reviewed publications: Journal of Biological Chemistry (JBC); Investigative Ophthalmology & Visual Science (IOVS); Federation of American Societies for Experimental Biology Journal (FASEB); PLOS ONE; Journal of Investigational Biochemistry; SLAS Discovery; and Human Molecular Genetics. Dr. Chen’s research interests include mechanism study and drug discovery of RHO associated retinitis pigmentosa; drug discovery of myocilin associated glaucoma; and the role of a purine metabolite in treating photoreceptor degeneration. The Chen Lab pharmacological and biochemical methods to study protein misfolding visual disorders. Target protein homeostaisis can be restored by pharmacological chaperones or small molecule inducers of misfolded protein clearance. Rhodopsin (RHO) protein misfolding causes retinitis pigmentosa, an inherited and progressive retinal degeneration that currently lacks an effective treatment. Her lab uses biochemical and pharmacological methods to identify and characterize potent and efficacious small molecules that either stabilizes the misfolded rhodopsin protein, or specifically clear the mutant protein. She and her team then analyze the efficacy of selected lead compounds in retinal explants or mouse models that are either susceptible to light-induced retinal degeneration or undergo a progressive retinal degeneration. As Dr. Chen works to develop an effective treatment for rhodopsin associated retinitis pigmentosa, she also uses the chemical genomic method to understand the structural properties of rhodopsin and its metabolism in rod photoreceptors. Similar to RHO-associated retinitis pigmentosa, mutations of Myocilin (MYOC) lead to its misfolding and retention in the endoplasmic reticulum and autosomal dominant glaucoma. The Chen lab is developing a drug discovery project looking for efficacious pharmacological chaperones of MYOC to treat this type of glaucoma. A third project of Chen lab is collaborative with Drs. Jose-Alain Sahel, Edwin Jackson and Lori Birder. They discovered an endogenous purine metabolite can effectively prevent photoreceptor degeneration in two rodent models of photoreceptor degeneration. They use a highly interdisciplinary methods to understand the mechanism of actions and to improve the efficacy and safety of the compound for treating photoreceptor degenerative diseases. Dr. Chen holds three pending patents for small molecule chaperones, degradation enhancers of rhodopsin, and retinal protecting compounds for age related retinal degeneration. View a partial list of Dr. Chen’s publications below: Liu X, Feng B, Vats A, Tang H, Seibel W, Swaroop M, Tawa G, Zheng W, Byrne L, Schurdak M, Chen Y. Pharmacological clearance of misfolded rhodopsin for the treatment of RHO-associated retinitis pigmentosa [published online ahead of print, 2020 Jun 14]. FASEB J. 2020;10.1096/fj.202000282R. doi:10.1096/fj.202000282R PMID: 32536017 Getter T, Gulati S, Zimmerman R, Chen Y, Vinberg F, Palczewski K. Stereospecific modulation of dimeric rhodopsin. FASEB J. 2019 Aug;33(8):9526-9539. doi: 10.1096/fj.201900443RR. Epub 2019 May 23. PubMed PMID: 31121099; PubMed Central PMCID: PMC6662988. Getter T, Suh S, Hoang T, Handa JT, Dong Z, Ma X, Chen Y, Blackshaw S, Palczewski K. The selective estrogen receptor modulator raloxifene mitigates the effect of all-trans-retinal toxicity in photoreceptor degeneration. J Biol Chem. 2019 Jun 14;294(24):9461-9475. doi: 10.1074/jbc.RA119.008697. Epub 2019 May 9. PubMed PMID: 31073029; PubMed Central PMCID: PMC6579480. Feng B, Liu X, Chen Y. A Rhodopsin Transport Assay by High-Content Imaging Analysis. J Vis Exp. 2019 Jan 16;(143). PubMed PMID: 30735172. 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;9(1):1976. PMID: 29773803. * 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. Pharmacological research. 2016;115:1-13. 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. 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. Investigative Ophthalmology & Visual Science. 2015;56(4):2553-67. PMID: 25783607. Chen Y, Tang H. High-throughput screening assays to identify small molecules preventing photoreceptor degeneration caused by the rhodopsin P23H mutation. Methods Mol Biol. 2015;1271:369-90. PubMed PMID: 25697536. 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. Molecular pharmacology. 2014;86(2):231-42. PMID: 24913940. Chen Y, Jastrzebska B, Cao P, Zhang J, Wang B, Sun W, Yuan Y, Feng Z, Palczewski K. Inherent instability of the retinitis pigmentosa P23H mutant opsin. J Biol Chem. 2014;289(13):9288-303. PMID: 24515108. Chen Y, Farquhar ER, Chance MR, Palczewski K, Kiser PD. Insights into substrate specificity and metal activation of mammalian tetrahedral aspartyl aminopeptidase. J Biol Chem. 2012;287(16):13356-70. PMID: 22356908. Chen Y, Basu R, Gleghorn ML, Murakami KS, Carey PR. Time-resolved events on the reaction pathway of transcript initiation by a single-subunit RNA polymerase: Raman crystallographic evidence. J Am Chem Soc. 2011;133(32):12544-55. PMID: 21744806. Chen Y, Eldho NV, Dayie TK, Carey PR. Probing adenine rings and backbone linkages using base specific isotope-edited Raman spectroscopy: application to group II intron ribozyme domain V. Biochemistry-Us. 2010;49(16):3427-35. PMID: 20225830. A complete list of Dr. Chen’s publications is here.