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Faculty Profile Last Modified Time: 01:42:15 PM Fri, 21 Jun 2013   Contact Information Yuhui (Whitney) Yin Associated Profiles  Associate Professor and Assistant Director, Pharmacology & Toxicology, UT Medical Branch at Galveston   Mail Box: 0617, Basic Science Bldg, Room No.: 3.110B    ywyin@utmb.edu     409-772-9631    Web Link    Mitochondrial DNA, Tryptophan-TRNA Ligase, DNA, Nucleotides, Holoenzymes    Associated Profiles Professional Preparation Research and Expertise Affiliations Appointments  Professional Preparation  Degree Major Institution Year  MD   Tianjin Medical College    PhD   University of North Carolina at Chapel Hill    Research and Expertise Research Interests   Structural and functional studies of antiviral drug toxicity: Antiviral drugs based on nucleoside analogs are effective inhibitors for viral reverse transcriptase and RNA polymerase, thus have been successfully used in treating HIV and HCV infections. With prolonged patients life span, the success of the drugs now has to be balanced with their drug toxicity. One of the major target of nucleoside analogs is human mitochondrial DNA polymerase, Pol Y. Because drug efficacy is not completely correlated with drug toxicity, we believe there is exploitable difference in designing potent, low toxic antiviral reagents. To reveal the structural differences between viral target protein and human adverse reaction target, we embarked on structural and functional studies of replicating human mitochondrial DNA polymerase or stalled by antiviral drugs. My laboratory determined the first crystal structures of human Pol Y holoenzyme. Recently, we determined structures of ternary complex of Pol Y-DNA with a substrate or an antiHIV reagent, zalcitabine, lamivudine or emtricitabine. These structures provided unprecedented insight in Pol Y mediated antiviral drug toxicity. As Pol Y mutations are associated with multisystem disorders, the structures have been widely used by basic scientists as well as clinicians to understand the detrimental effects of the mutations. I directed all of these studies. Mitochondrial DNA repair: Mitochondria contain high concentrations of reactive oxygen species (ROS) due to intrinsic radicals generated through metabolic reactions and extrinsic factors such as anticancer radiation therapy. Consequently, mitochondrial DNA suffers higher likelihood for oxidative damages than chromosomal DNA. While the overall scheme follows that of nuclear BER, mitochondrial BER has distinct differences. Pol Y is responsible for DNA synthesis during replication and repair. I lead investigation of Pol Y activity in BER specific gap-filling DNA synthesis. Our findings indicate Pol Y is very inefficient on 1-nt gapped DNA and no strand displacement synthesis activity, suggesting that the polymerase alone is inefficient to carry out mitochondrial BER function, supporting the importance of repair complex. We studied Pol Y replication on damaged DNA. We recent started structural and functional studies of components of mitochondrial DNA repair complex with a long-term goal of structural determination of the entire mitochondrial DNA repairsome. I am the PI of these studies.  Publications/Creative Works Click here to search for this faculty member's publications on PubMed.  Affiliations  Research Consortia GCC Cluster for Cellular and Molecular Biophysics  Appointments Title Department / School Institution Associate Professor and Assistant Director Pharmacology & Toxicology UT Medical Branch at Galveston

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