Yuanyuan Chen, PhD

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

Academic Affiliation

2017-Present  Assistant Professor, Ophthalmology, University of Pittsburgh School of Medicin
2011-2017       Postdoctoral Scholar, Labotory of Krzysztof Palczewski, Department of Pharmacology, Case Western Reserve University
2004-2010       Doctoral Research, Laboratory of Dr. Paul Carey, Department of Biochemistry, Case Western Reserve University
2002-2004       Undergraduate Research, Laboratory of Dr. Hong Lv, Fudan University

Education & Training

  • 2004-2010 Case Western Reserve University, Ph.D in Biochemistry
  • 1999-2003 Fudan University, B.S in Biological Sciences

Representative Publications

  1. 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.
     
  2. 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.
     
  3. 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.
     
  4. 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.
     
  5. 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.
     
  6. 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.
     
  7. 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.
     
  8. 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.
     
  9. 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.

Research Interest Summary

Systems Pharmacology of Retinal Degeneration Laboratory

Research Interests

Lab personnel
Bing Feng, Ph.D., Postdoctoral Associate, Ophthalmology

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. Our 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. We then analyzes the efficacy of selected lead compounds in mouse models that either susceptible to light-induced retinal degeneration or undergo a progressive retinal degeneration. On our journey of developing effective treatment for rhodopsin associated retinitis pigmentosa, we also use chemical genomic method to understand the structural properties of rhodopsin and its metabolism in rod photoreceptors. 

Research Grants

National Eye Institute (R00-EY024992): 08/01/17-06/30/20.
“Drug Discovery and Mechanistic Study of P23H Rhodopsin Associated Retinitis Pigmentosa”