Professional Education


  • Doctor of Philosophy, Seoul National University (2020)
  • Bachelor of Science, University of Auckland (2015)

Stanford Advisors


All Publications


  • Specific ablation of PDGFRbeta-overexpressing pericytes with antibody-drug conjugate potently inhibits pathologic ocular neovascularization in mouse models. Communications medicine Lee, S. J., Kim, S., Jo, D. H., Cho, C. S., Kim, S. R., Kang, D., Chae, J., Yoo, D. K., Ha, S., Chung, J., Kim, J. H. 2021; 1: 58

    Abstract

    Background: Crosstalk between pericytes and endothelial cells is critical for ocular neovascularization. Endothelial cells secrete platelet-derived growth factor (PDGF)-BB and recruit PDGF receptor beta (PDGFRbeta)-overexpressing pericytes, which in turn cover and stabilize neovessels, independent of vascular endothelial growth factor (VEGF). Therapeutic agents inhibiting PDGF-BB/PDGFRbeta signaling were tested in clinical trials but failed to provide additional benefits over anti-VEGF agents. We tested whether an antibody-drug conjugate (ADC) - an engineered monoclonal antibody linked to a cytotoxic agent - could selectively ablate pericytes and suppress retinal and choroidal neovascularization.Methods: Immunoblotting, flow cytometry, cell viability test, and confocal microscopy were conducted to assess the internalization and cytotoxic effect of ADC targeting mPDGFRbeta in an in vitro setting. Immunofluorescence staining of whole-mount retinas and retinal pigment epithelium-choroid-scleral complexes, electroretinography, and OptoMotry test were used to evaluate the effect and safety of ADC targeting mPDGFRbeta in the mouse models of pathologic ocular neovascularization.Results: ADC targeting mPDGFRbeta is effectively internalized into mouse brain vascular pericytes and showed significant cytotoxicity compared with the control ADC. We also show that specific ablation of PDGFRbeta-overexpressing pericytes using an ADC potently inhibits pathologic ocular neovascularization in mouse models of oxygen-induced retinopathy and laser-induced choroidal neovascularization, while not provoking generalized retinal toxicity.Conclusion: Our results suggest that removing PDGFRbeta-expressing pericytes by an ADC targeting PDGFRbeta could be a potential therapeutic strategy for pathologic ocular neovascularization.

    View details for DOI 10.1038/s43856-021-00059-3

    View details for PubMedID 35602228