URee Chon

All Publications

• Aging drives cerebrovascular network remodeling and functional changes in the mouse brain. Nature communications Bennett, H. C., Zhang, Q., Wu, Y. T., Manjila, S. B., Chon, U., Shin, D., Vanselow, D. J., Pi, H. J., Drew, P. J., Kim, Y. 2024; 15 (1): 6398

  Abstract

  Aging is frequently associated with compromised cerebrovasculature and pericytes. However, we do not know how normal aging differentially impacts vascular structure and function in different brain areas. Here we utilize mesoscale microscopy methods and in vivo imaging to determine detailed changes in aged murine cerebrovascular networks. Whole-brain vascular tracing shows an overall ~10% decrease in vascular length and branching density with ~7% increase in vascular radii in aged brains. Light sheet imaging with 3D immunolabeling reveals increased arteriole tortuosity of aged brains. Notably, vasculature and pericyte densities show selective and significant reductions in the deep cortical layers, hippocampal network, and basal forebrain areas. We find increased blood extravasation, implying compromised blood-brain barrier function in aged brains. Moreover, in vivo imaging in awake mice demonstrates reduced baseline and on-demand blood oxygenation despite relatively intact neurovascular coupling. Collectively, we uncover regional vulnerabilities of cerebrovascular network and physiological changes that can mediate cognitive decline in normal aging.

  View details for DOI 10.1038/s41467-024-50559-8

  View details for PubMedID 39080289

  View details for PubMedCentralID PMC11289283

• In situ cell-type-specific cell-surface proteomic profiling in mice. Neuron Shuster, S. A., Li, J., Chon, U., Sinantha-Hu, M. C., Luginbuhl, D. J., Udeshi, N. D., Carey, D. K., Takeo, Y. H., Xie, Q., Xu, C., Mani, D. R., Han, S., Ting, A. Y., Carr, S. A., Luo, L. 2022

  Abstract

  Cell-surface proteins (CSPs) mediate intercellular communication throughout the lives of multicellular organisms. However, there are no generalizable methods for quantitative CSP profiling in specific cell types in vertebrate tissues. Here, we present in situ cell-surface proteome extraction by extracellular labeling (iPEEL), a proximity labeling method in mice that enables spatiotemporally precise labeling of cell-surface proteomes in a cell-type-specific environment in native tissues for discovery proteomics. Applying iPEEL to developing and mature cerebellar Purkinje cells revealed differential enrichment in CSPs with post-translational protein processing and synaptic functions in the developing and mature cell-surface proteomes, respectively. A proteome-instructed in vivo loss-of-function screen identified a critical, multifaceted role for Armh4 in Purkinje cell dendrite morphogenesis. Armh4 overexpression also disrupts dendrite morphogenesis; this effect requires its conserved cytoplasmic domain and is augmented by disrupting its endocytosis. Our results highlight the utility of CSP profiling in native mammalian tissues for identifying regulators of cell-surface signaling.

  View details for DOI 10.1016/j.neuron.2022.09.025

  View details for PubMedID 36220098

• In Situ Cell-Surface Proteomics: Method Development and Applications in Neurobiology Li, J., Han, S., Xie, Q., Shuster, S. A., Li, H., Udeshi, N. D., Svinkina, T., Carey, D. K., Mani, D. R., Xu, C., Guajardo, R., Chon, U., Luginbuhl, D. J., McLaughlin, C. N., Takeo, Y. H., Li, T., Orlin, D., Hu, M. C., Kohani, S., Wu, B., Xie, A., Kaewsapsak, P., Murthy, S. E., Quake, S. R., Carr, S. A., Ting, A. Y., Luo, L. ELSEVIER. 2022: S71

  View details for DOI 10.1016/j.mcpro.2022.100382

  View details for Web of Science ID 000898188800091

• Quantitative relationship between the cerebrovascular network and neuronal cell types in mice Wu, Y., Bennett, H., Chon, U. R., Vanselow, D., Zhang, Q., Munoz-Castaneda, R., Cheng, K., Osten, P., Drew, P., Kim, Y. SAGE PUBLICATIONS INC. 2022: 316-317

  View details for Web of Science ID 000802263300536