Stanford Advisors

  • Yang Sun, Postdoctoral Faculty Sponsor

All Publications

  • Base editing correction of OCRL in Lowe syndrome: ABE-mediated functional rescue in patient-derived fibroblasts. Human molecular genetics Chen, S., Lo, C. H., Liu, Z., Wang, Q., Ning, K., Li, T., Sun, Y. 2024


    Lowe syndrome, a rare X-linked multisystem disorder presenting with major abnormalities in the eyes, kidneys, and central nervous system, is caused by mutations in OCRL gene (NG_008638.1). Encoding an inositol polyphosphate 5-phosphatase, OCRL catalyzes the hydrolysis of PI(4,5)P2 into PI4P. There are no effective targeted treatments for Lowe syndrome. Here, we demonstrate a novel gene therapy for Lowe syndrome in patient fibroblasts using an adenine base editor (ABE) that can efficiently correct pathogenic point mutations. We show that ABE8e-NG-based correction of a disease-causing mutation in a Lowe patient-derived fibroblast line containing R844X mutation in OCRL gene, restores OCRL expression at mRNA and protein levels. It also restores cellular abnormalities that are hallmarks of OCRL dysfunction, including defects in ciliogenesis, microtubule anchoring, α-actinin distribution, and F-actin network. The study indicates that ABE-mediated gene therapy is a feasible treatment for Lowe syndrome, laying the foundation for therapeutic application of ABE in the currently incurable disease.

    View details for DOI 10.1093/hmg/ddae045

    View details for PubMedID 38557732

  • Compartmentalized ciliation changes of oligodendrocytes in aged mouse optic nerve. Journal of neuroscience research Ning, K., Tran, M., Kowal, T. J., Mesentier-Louro, L. A., Sendayen, B. E., Wang, Q., Lo, C. H., Li, T., Majumder, R., Luo, J., Hu, Y., Liao, Y. J., Sun, Y. 2024; 102 (1): e25273


    Primary cilia are microtubule-based sensory organelles that project from the apical surface of most mammalian cells, including oligodendrocytes, which are myelinating cells of the central nervous system (CNS) that support critical axonal function. Dysfunction of CNS glia is associated with aging-related white matter diseases and neurodegeneration, and ciliopathies are known to affect CNS white matter. To investigate age-related changes in ciliary profile, we examined ciliary length and frequency in the retinogeniculate pathway, a white matter tract commonly affected by diseases of aging but in which expression of cilia has not been characterized. We found expression of Arl13b, a marker of primary cilia, in a small group of Olig2-positive oligodendrocytes in the optic nerve, optic chiasm, and optic tract in young and aged C57BL/6 wild-type mice. While the ciliary length and ciliated oligodendrocyte cells were constant in young mice in the retinogeniculate pathway, there was a significant increase in ciliary length in the anterior optic nerve as compared to the aged animals. Morphometric analysis confirmed a specific increase in the ciliation rate of CC1+ /Olig2+ oligodendrocytes in aged mice compared with young mice. Thus, the prevalence of primary cilia in oligodendrocytes in the visual pathway and the age-related changes in ciliation suggest that they may play important roles in white matter and age-associated optic neuropathies.

    View details for DOI 10.1002/jnr.25273

    View details for PubMedID 38284846

  • Effect of Brimonidine on Retinal Ganglion Cell Function by in vivo Calcium Imaging in Glaucoma Mice Model Li, T., Wang, Q., Lo, C., Ning, K., Majumder, R., Sun, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2023
  • Age-Associated Changes in Astrocytes Cilia of Mouse Retina and Optic Nerve Majumder, R., Ning, K., Kowal, T., Wang, Q., Tran, M., Wang, B., Hu, Y., Liao, Y., Sun, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
  • Defective Microtubule-Based Transporters Alter Basal mTORC1 And Akt Signaling in Lowe Syndrome Patient-Derived Cells Wang, Q., Wang, B., Kowal, T., Hu, Y., Sun, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
  • Differences in primary cilia amongst retinal ganglion cell subtypes Kowal, T., Dhande, O., Ning, K., Wang, B., Wang, Q., Liu, W., Berbari, N., Hu, Y., Sun, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
  • Increased ciliary length of oligodendrocytes in anterior optic nerve with ageing Tran, M., Ning, K., Kowal, T., Majumder, R., Wang, Q., Hu, Y., Liao, Y., Sun, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2022
  • Distribution of prototypical primary cilia markers in subtypes of retinal ganglion cells. The Journal of comparative neurology Kowal, T. J., Dhande, O. S., Wang, B., Wang, Q., Ning, K., Liu, W., Berbari, N. F., Hu, Y., Sun, Y. 2022


    Loss of retinal ganglion cells (RGCs) underlies several forms of retinal disease including glaucomatous optic neuropathy, a leading cause of irreversible blindness. Several rare genetic disorders associated with cilia dysfunction have retinal degeneration as a clinical hallmark. Much of the focus of ciliopathy associated blindness is on the connecting cilium of photoreceptors; however, RGCs also possess primary cilia. It is unclear what roles RGC cilia play, what proteins and signaling machinery localize to RGC cilia, or how RGC cilia are differentiated across the subtypes of RGCs. To better understand these questions, we assessed the presence or absence of a prototypical cilia marker Arl13b and a widely distributed neuronal cilia marker AC3 in different subtypes of mouse RGCs. Interestingly, not all RGC subtype cilia are the same and there are significant differences even among these standard cilia markers. Alpha-RGCs positive for osteopontin, calretinin, and SMI32 primarily possess AC3-positive cilia. Directionally selective RGCs that are CART positive or Trhr positive localize either Arl13b or AC3, respectively, in cilia. Intrinsically photosensitive RGCs differentially localize Arl13b and AC3 based on melanopsin expression. Taken together, we characterized the localization of gold standard cilia markers in different subtypes of RGCs and conclude that cilia within RGC subtypes may be differentially organized. Future studies aimed at understanding RGC cilia function will require a fundamental ability to observe the cilia across subtypes as their signaling protein composition is elucidated. A comprehensive understanding of RGC cilia may reveal opportunities to understanding how their dysfunction leads to retinal degeneration.

    View details for DOI 10.1002/cne.25326

    View details for PubMedID 35434813