Academic Appointments

  • Basic Life Science Research Associate, Bioengineering

All Publications

  • Cryogenic electron microscopy and tomography reveal imperfect icosahedral symmetry in alphaviruses. PNAS nexus Chmielewski, D., Su, G. C., Kaelber, J. T., Pintilie, G. D., Chen, M., Jin, J., Auguste, A. J., Chiu, W. 2024; 3 (3): pgae102


    Alphaviruses are spherical, enveloped RNA viruses with two-layered icosahedral architecture. The structures of many alphaviruses have been studied using cryogenic electron microscopy (cryo-EM) reconstructions, which impose icosahedral symmetry on the viral particles. Using cryogenic electron tomography (cryo-ET), we revealed a polarized symmetry defect in the icosahedral lattice of Chikungunya virus (CHIKV) in situ, similar to the late budding particles, suggesting the inherent imperfect symmetry originates from the final pinch-off of assembled virions. We further demonstrated this imperfect symmetry is also present in in vitro purified CHIKV and Mayaro virus, another arthritogenic alphavirus. We employed a subparticle-based single-particle analysis protocol to circumvent the icosahedral imperfection and boosted the resolution of the structure of the CHIKV to ∼3 Å resolution, which revealed detailed molecular interactions between glycoprotein E1-E2 heterodimers in the transmembrane region and multiple lipid-like pocket factors located in a highly conserved hydrophobic pocket. This complementary use of in situ cryo-ET and single-particle cryo-EM approaches provides a more precise structural description of near-icosahedral viruses and valuable insights to guide the development of structure-based antiviral therapies against alphaviruses.

    View details for DOI 10.1093/pnasnexus/pgae102

    View details for PubMedID 38525304

    View details for PubMedCentralID PMC10959069

  • Promotion of homology-directed DNA repair by polyamines NATURE COMMUNICATIONS Lee, C., Su, G., Huang, W., Ko, M., Yeh, H., Chang, G., Lin, S., Chi, P. 2019; 10: 65


    Polyamines, often elevated in cancer cells, have been shown to promote cell growth and proliferation. Whether polyamines regulate other cell functions remains unclear. Here, we explore whether and how polyamines affect genome integrity. When DNA double-strand break (DSB) is induced in hair follicles by ionizing radiation, reduction of cellular polyamines augments dystrophic changes with delayed regeneration. Mechanistically, polyamines facilitate homologous recombination-mediated DSB repair without affecting repair via non-homologous DNA end-joining and single-strand DNA annealing. Biochemical reconstitution and functional analyses demonstrate that polyamines enhance the DNA strand exchange activity of RAD51 recombinase. The effect of polyamines on RAD51 stems from their ability to enhance the capture of homologous duplex DNA and synaptic complex formation by the RAD51-ssDNA nucleoprotein filament. Our work demonstrates a novel function of polyamines in the maintenance of genome integrity via homology-directed DNA repair.

    View details for DOI 10.1038/s41467-018-08011-1

    View details for Web of Science ID 000455102900004

    View details for PubMedID 30622262

    View details for PubMedCentralID PMC6325121