Yuanyuan Chen, PhD

Dr. Yuanyuan Chen is an Assistant Professor, Department of Ophthalmology, University of Pittsburgh.  Prior to coming to Pitt in 2017, Dr. Chen was a Senior Research Associate, Department of Pharmacology, Case Western Reserve University, Cleveland, OH. 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. Dr. Chen is a member of the Association for Research in Vision and Ophthalmology (ARVO) and the Sigma Xi Scientific Research Society.  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
• Chemistry of Life (Chinese)
• Chemistry Reports (Chinese)

Dr. Chen’s research interests include:

1. Disease mechanism study and drug discovery of retinitis pigmentosa associated with rhodopsin P23H mutation
2. Roles of histone deacetylases in retinal degeneration
3. Physiological function of aspartyl aminopeptidase (DNPEP) in the retina

The Chen Lab uses small molecules to mitigate retinal degeneration by restoring the homeostasis of misfolded proteins. Many inherited retinal degenerations can be classified as protein misfolding diseases. Retinitis pigmentosa is an inherited and progressive retinal degeneration that currently lacks an effective treatment. A total of more than 150 rhodopsin mutations were found in about 30% of all autosomal dominant retinitis pigmentosa cases. A large portion of rhodopsin mutations can be classified in Class II mutations carrying folding defects. 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 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. View a list of Dr. Chen’s publications here: 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. 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. Investigative Ophthalmology & Visual Science. 2015;56(4):2553-67. PubMed PMID: 25783607 PMCID: PMC4554260. 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. PubMed PMID: 24913940 PMCID: PMC4127928. 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. PubMed PMID: 24515108 PMCID: PMC3979360. 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. PubMed PMID: 22356908 PMCID: PMC3339940. 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. PubMed PMID: 21744806 PMCID: PMC3154994. 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. PubMed PMID: 20225830 PMCID: PMC2863103.