Bio


Dr. Ning currently joins Dr. Yang Sun’s lab as a postdoctoral fellow at Dept. of Ophthalmology, Stanford University. Her current research interests include cilia-mediated signaling in RPE-related diseases and glaucoma. Dr. Ning received her MD at Xiamen University in China and completed her internship at Zhongshan Hospital Affiliated with Xiamen University. Her long-term research interest is to understand primary cilia roles in ocular development and how alterations in cilia-related gene expression contribute to eye diseases. Her further goal is to be a physician-scientist and to translate scientific discoveries to patient therapies. Some of her hobbies are cycling, reading, and skiing.

Honors & Awards


  • Macular Degeneration Research Postdoctoral Fellowship Award, BrightFocus Foundation (2021-2023)
  • The 2020 Alston Callahan, MD Postdoctoral Scholar, International Retinal Research Foundation (2020-2021)

Professional Education


  • MD, Xiamen University (2019)

Patents


  • Ke Ning etc.. "China P.Rep. Patent 201720157302.9 A device for generating murine sleep deprivation model", Xiamen University, Jan 2, 0189

All Publications


  • Optogenetic stimulation of phosphoinositides reveals a critical role of primary cilia in eye pressure regulation SCIENCE ADVANCES Prosseda, P. P., Alvarado, J. A., Wang, B., Kowal, T. J., Ning, K., Stamer, W., Hu, Y., Sun, Y. 2020; 6 (18)
  • Defective INPP5E distribution in NPHP1-related Senior-Loken syndrome. Molecular genetics & genomic medicine Ning, K. n., Song, E. n., Sendayen, B. E., Prosseda, P. P., Chang, K. C., Ghaffarieh, A. n., Alvarado, J. A., Wang, B. n., Haider, K. M., Berbari, N. F., Hu, Y. n., Sun, Y. n. 2020: e1566

    Abstract

    Senior-Loken syndrome is a rare genetic disorder that presents with nephronophthisis and retinal degeneration, leading to end-stage renal disease and progressive blindness. The most frequent cause of juvenile nephronophthisis is a mutation in the nephronophthisis type 1 (NPHP1) gene. NPHP1 encodes the protein nephrocystin-1, which functions at the transition zone (TZ) of primary cilia.We report a 9-year-old Senior-Loken syndrome boy with NPHP1 deletion, who presents with bilateral vision decrease and cystic renal disease. Renal function deteriorated to require bilateral nephrectomy and renal transplant. We performed immunohistochemistry, H&E staining, and electron microscopy on the renal sample to determine the subcellular distribution of ciliary proteins in the absence of NPHP1.Immunohistochemistry and electron microscopy of the resected kidney showed disorganized cystic structures with loss of cilia in renal tubules. Phosphoinositides have been recently recognized as critical components of the ciliary membrane and immunostaining of kidney sections for phosphoinositide 5-phosphatase, INPP5E, showed loss of staining compared to healthy control. Ophthalmic examination showed decreased electroretinogram consistent with early retinal degeneration.The decreased expression of INPP5E specifically in the primary cilium, coupled with disorganized cilia morphology, suggests a novel role of NPHP1 that it is involved in regulating ciliary phosphoinositide composition in the ciliary membrane of renal tubular cells.

    View details for DOI 10.1002/mgg3.1566

    View details for PubMedID 33306870

  • Developmental Distribution of Primary Cilia in the Retinofugal Visual Pathway. The Journal of comparative neurology Alvarado, J. A., Dhande, O. S., Prosseda, P. P., Kowal, T. J., Ning, K. n., Jabbehdari, S. n., Hu, Y. n., Sun, Y. n. 2020

    Abstract

    The mammalian visual system is composed of circuitry connecting sensory input from the retina to the processing core of the visual cortex. The two main retinorecipient brain targets, the superior colliculus (SC) and dorsal lateral geniculate nucleus (dLGN), bridge retinal input and visual output. The primary cilium is a conserved organelle increasingly viewed as a critical sensor for the regulation of developmental and homeostatic pathways in most mammalian cell types. Moreover, cilia have been described as crucial for neurogenesis, neuronal maturation, and survival in the cortex and retina. However, cilia in the visual relay center remain to be fully described. In this study, we characterized the ciliation profile of the SC and dLGN and found that the overall number of ciliated cells declined during development. Interestingly, shorter ciliated cells in both regions were identified as neurons, whose numbers remained stable over time, suggesting that cilia retention is a critical feature for optimal neuronal function in SC and dLGN. Our study suggests that primary cilia are important for neuronal maturation and function in cells of the SC and dLGN.

    View details for DOI 10.1002/cne.25029

    View details for PubMedID 32939774

  • Oculocerebrorenal Syndrome of Lowe: Characterizations of Ocular Presentation and Management Ma, X., Ning, K., Kowal, T., Sun, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
  • The Role of Phosphoinositides in Aqueous Humor Dynamics via Optogenetic Stimulation in the Trabecular Meshwork Alvarado, J., Prosseda, P., Ning, K., Kowal, T., Wang, B., Hu, Y., Sun, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
  • Role of inositol phosphatase OCRL in microtubule nucleation: Implications for Oculocerebrorenal Syndrome of Lowe Kowal, T., Wang, B., Prosseda, P., Alvarado, J., He, W., Ning, K., Hu, Y., Sun, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
  • Characterization of primary cilia in mouse retina during retinal development Ning, K., Kowal, T., Chang, K., Alvarado, J., Silva, R., Kreymerman, A., Mahajan, V. B., Hu, Y., Sun, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2019
  • Review of Ocular Manifestations of Joubert Syndrome GENES Wang, S. F., Kowal, T. J., Ning, K., Koo, E. B., Wu, A. Y., Mahajan, V. B., Sun, Y. 2018; 9 (12)
  • The role of inositol phosphatase OCRL in microtubule nucleation: Implications for Oculocerebrorenal Syndrome of Lowe Wang, B., Prosseda, P. P., He, W., Kowal, T., Alvarado, J. A., Ning, K., Sun, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
  • Ocular and renal phenotypes of NPHP1 deletion in Senior Loken syndrome Ning, K., Song, E., Haider, K. M., Ghaffarieh, A., Alvarado, J. A., Sun, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
  • Optogenetic Regulation of Aqueous Outflow in Mouse Trabecular Meshwork Alvarado, J. A., Prosseda, P. P., Luo, N., Wang, B., Ning, K., He, W., Kowal, T., Sun, Y. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018
  • Sleep deprivation disrupts the lacrimal system and induces dry eye disease. Experimental & molecular medicine Li, S. n., Ning, K. n., Zhou, J. n., Guo, Y. n., Zhang, H. n., Zhu, Y. n., Zhang, L. n., Jia, C. n., Chen, Y. n., Sol Reinach, P. n., Liu, Z. n., Li, W. n. 2018; 50 (3): e451

    Abstract

    Sleep deficiency is a common public health problem associated with many diseases, such as obesity and cardiovascular disease. In this study, we established a sleep deprivation (SD) mouse model using a 'stick over water' method and observed the effect of sleep deficiency on ocular surface health. We found that SD decreased aqueous tear secretion; increased corneal epithelial cell defects, corneal sensitivity, and apoptosis; and induced squamous metaplasia of the corneal epithelium. These pathological changes mimic the typical features of dry eye. However, there was no obvious corneal inflammation and conjunctival goblet cell change after SD for 10 days. Meanwhile, lacrimal gland hypertrophy along with abnormal lipid metabolites, secretory proteins and free amino-acid profiles became apparent as the SD duration increased. Furthermore, the ocular surface changes induced by SD for 10 days were largely reversed after 14 days of rest. We conclude that SD compromises lacrimal system function and induces dry eye. These findings will benefit the clinical diagnosis and treatment of sleep-disorder-related ocular surface diseases.

    View details for DOI 10.1038/emm.2017.285

    View details for PubMedID 29497171

    View details for PubMedCentralID PMC5898890

  • Ectodysplasin A regulates epithelial barrier function through sonic hedgehog signalling pathway. Journal of cellular and molecular medicine Li, S. n., Zhou, J. n., Zhang, L. n., Li, J. n., Yu, J. n., Ning, K. n., Qu, Y. n., He, H. n., Chen, Y. n., Reinach, P. S., Liu, C. Y., Liu, Z. n., Li, W. n. 2018; 22 (1): 230–40

    Abstract

    Ectodysplasin A (Eda), a member of the tumour necrosis factor superfamily, plays an important role in ectodermal organ development. An EDA mutation underlies the most common of ectodermal dysplasias, that is X-linked hypohidrotic ectodermal dysplasia (XLHED) in humans. Even though it lacks a developmental function, the role of Eda during the postnatal stage remains elusive. In this study, we found tight junctional proteins ZO-1 and claudin-1 expression is largely reduced in epidermal, corneal and lung epithelia in Eda mutant Tabby mice at different postnatal ages. These declines are associated with tail ulceration, corneal pannus formation and lung infection. Furthermore, topical application of recombinant Eda protein markedly mitigated corneal barrier dysfunction. Using cultures of a human corneal epithelial cell line and Tabby mouse skin tissue explants, Eda up-regulated expression of ZO-1 and claudin-1 through activation of the sonic hedgehog signalling pathway. We conclude that EDA gene expression contributes to the maintenance of epithelial barrier function. Such insight may help efforts to identify novel strategies for improving management of XLHED disease manifestations in a clinical setting.

    View details for DOI 10.1111/jcmm.13311

    View details for PubMedID 28782908

    View details for PubMedCentralID PMC5742694

  • Ectodysplasin A protein promotes corneal epithelial cell proliferation. The Journal of biological chemistry Li, S. n., Zhou, J. n., Bu, J. n., Ning, K. n., Zhang, L. n., Li, J. n., Guo, Y. n., He, X. n., He, H. n., Cai, X. n., Chen, Y. n., Reinach, P. S., Liu, Z. n., Li, W. n. 2017; 292 (32): 13391–401

    Abstract

    The EDA gene encodes ectodysplasin A (Eda), which if mutated causes X-linked hypohidrotic ectodermal dysplasia (XLHED) disease in humans. Ocular surface changes occur in XLHED patients whereas its underlying mechanism remains elusive. In this study, we found Eda was highly expressed in meibomian glands, and it was detected in human tears but not serum. Corneal epithelial integrity was defective and the thickness was reduced in the early postnatal stage of Eda mutant Tabby mice. Corneal epithelial cell proliferation decreased and the epithelial wound healing was delayed in Tabby mice, whereas it was restored by exogenous Eda. Eda exposure promoted mouse corneal epithelial wound healing during organ culture, whereas scratch wound assay showed that it did not affect human corneal epithelial cell line migration. Epidermal growth factor receptor (EGFR), phosphorylated EGFR (p-EGFR), and phosphorylated ERK1/2 (p-ERK) were down-regulated in Tabby mice corneal epithelium. Eda treatment up-regulated the expression of Ki67, EGFR, p-EGFR, and p-ERK in human corneal epithelial cells in a dose-dependent manner. In conclusion, Eda protein can be secreted from meibomian glands and promotes corneal epithelial cell proliferation through regulation of the EGFR signaling pathway. Eda release into the tears plays an essential role in the maintenance of corneal epithelial homeostasis.

    View details for DOI 10.1074/jbc.M117.803809

    View details for PubMedID 28655773

    View details for PubMedCentralID PMC5555198