Yuanyuan Chen, PhD

  • Assistant Professor of Ophthalmology
  • Systems Pharmacology Laboratory
  • University of Pittsburgh School of Medicine

Academic Affiliation

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

Education

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

Representative Publications

  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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

Systems Pharmacology Laboratory

Research Interests

Lab personnel
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

Research Grants

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