Bio

Clinical Focus


  • Pediatric Pulmonary

Academic Appointments


Professional Education


  • Board Certification: Pediatric Pulmonary, American Board of Pediatrics (2010)
  • Board Certification: Pediatrics, American Board of Pediatrics (2007)
  • Fellowship:Lucile Packard Children's Hospital (2011) CA
  • Residency:Children's Hospital Oakland (2007) CA
  • Medical Education:Saint Louis University School of Medicine (2004) MO

Publications

All Publications


  • Formation of a Neurosensory Organ by Epithelial Cell Slithering CELL Kuo, C. S., Krasnow, M. A. 2015; 163 (2): 394-405

    Abstract

    Epithelial cells are normally stably anchored, maintaining their relative positions and association with the basement membrane. Developmental rearrangements occur through cell intercalation, and cells can delaminate during epithelial-mesenchymal transitions and metastasis. We mapped the formation of lung neuroepithelial bodies (NEBs), innervated clusters of neuroendocrine/neurosensory cells within the bronchial epithelium, revealing a targeted mode of cell migration that we named "slithering," in which cells transiently lose epithelial character but remain associated with the membrane while traversing neighboring epithelial cells to reach cluster sites. Immunostaining, lineage tracing, clonal analysis, and live imaging showed that NEB progenitors, initially distributed randomly, downregulate adhesion and polarity proteins, crawling over and between neighboring cells to converge at diametrically opposed positions at bronchial branchpoints, where they reestablish epithelial structure and express neuroendocrine genes. There is little accompanying progenitor proliferation or apoptosis. Activation of the slithering program may explain why lung cancers arising from neuroendocrine cells are highly metastatic.

    View details for DOI 10.1016/j.cell.2015.09.021

    View details for Web of Science ID 000362952700016

    View details for PubMedID 26435104

  • Cellular mechanisms of alveolar pathology in childhood interstitial lung diseases: current insights from mouse genetics CURRENT OPINION IN PEDIATRICS Kuo, C. S., Desai, T. J. 2015; 27 (3): 341-347

    Abstract

    Childhood interstitial lung diseases (ILDs) are a diverse class of disorders affecting the alveolar gas exchange region that lack specific treatments and are usually fatal. Here, we integrate recent insights into alveolar cell biology with histopathology from well characterized mutations of surfactant-associated genes. We take a reductionist approach by parsing discrete histological features and correlating each to perturbation of a particular function of the alveolar epithelial type II (AT2) cell, the central driver of disease, to generate a working model for the cellular mechanisms of disease pathogenesis.The application of genetically modified mice and single cell genomics has yielded new insights into lung biology, including the identification of a bipotent alveolar progenitor in development, mapping of adult AT2 stem cells in vivo, and demonstration that latent cooperative interactions with fibroblasts can be pathologically activated by targeted injury of the AT2 cell.As we learn more about individual and cooperative roles for alveolar cells in health, we can dissect how perturbations of specific cellular functions contribute to disease in childhood ILDs. We hope our updated model centered around the AT2 cell as the initiator of disease provides a cellular framework that researchers can build upon and revise as they identify the specific molecular signals within and between alveolar cells that mediate the diverse pathologic features, so that targeted pharmacologic and cell-based treatments for patients can ultimately be engineered.

    View details for DOI 10.1097/MOP.0000000000000227

    View details for Web of Science ID 000354214800013

    View details for PubMedID 25888154

  • Interstitial lung disease in children CURRENT OPINION IN PEDIATRICS Kuo, C. S., Young, L. R. 2014; 26 (3): 320-327

    Abstract

    There has been tremendous progress in the approach to childhood interstitial lung diseases (chILD), with particular recognition that interstitial lung disease (ILD) in infants is often distinct from the forms that occur in older children and adults. Diagnosis is challenging because of the rarity of ILD and the fact that the presenting symptoms of ILD often overlap those of common respiratory disorders. This review summarizes the newly published recommendations for diagnosis and management, and highlights the recent scientific advances in several specific forms of chILD.Clinical practice guidelines emphasize the role for chest computed tomography, genetic testing, and lung biopsy in the diagnostic evaluation of children with suspected ILD. Recent studies have better defined the characteristics and molecular understanding of several different forms of ILD, including neuroendocrine cell hyperplasia of infancy and ILD, due to mutations in genes affecting surfactant production and metabolism. Despite significant progress, definitive therapies are often lacking.chILD encompasses a collection of rare, diffuse lung diseases. Timely recognition of children with suspected ILD and initiation of appropriate diagnostic evaluations will facilitate medical management. Systematic approaches to clinical care and further studies are needed to improve the outcomes of children with these rare disorders.

    View details for DOI 10.1097/MOP.0000000000000094

    View details for Web of Science ID 000335956800010

    View details for PubMedID 24752172

  • PML-dependent apoptosis after DNA damage is regulated by the checkpoint kinase hCds1/Chk2 NATURE CELL BIOLOGY Yang, S. T., Kuo, C., Bisi, J. E., Kim, M. K. 2002; 4 (11): 865-870

    Abstract

    The promyelocytic leukaemia (PML) gene is translocated in most acute promyelocytic leukaemias and encodes a tumour suppressor protein. PML is involved in multiple apoptotic pathways and is thought to be pivotal in gamma irradiation-induced apoptosis. The DNA damage checkpoint kinase hCds1/Chk2 is necessary for p53-dependent apoptosis after gamma irradiation. In addition, gamma irradiation-induced apoptosis also occurs through p53-independent mechanisms, although the molecular mechanism remains largely unknown. Here, we report that hCds1/Chk2 mediates gamma irradiation-induced apoptosis in a p53-independent manner through an ataxia telangiectasia-mutated (ATM)-hCds1/Chk2-PML pathway. Our results provide the first evidence of a functional relationship between PML and a checkpoint kinase in gamma irradiation-induced apoptosis.

    View details for DOI 10.1038/ncb869

    View details for Web of Science ID 000179137700015

    View details for PubMedID 12402044

  • Localization, dynamics, and protein interactions reveal distinct roles for ER and Golgi SNAREs JOURNAL OF CELL BIOLOGY Hay, J. C., Klumperman, J., Oorschot, V., Steegmaier, M., Kuo, C. S., Scheller, R. H. 1998; 141 (7): 1489-1502

    Abstract

    ER-to-Golgi transport, and perhaps intraGolgi transport involves a set of interacting soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins including syntaxin 5, GOS-28, membrin, rsec22b, and rbet1. By immunoelectron microscopy we find that rsec22b and rbet1 are enriched in COPII-coated vesicles that bud from the ER and presumably fuse with nearby vesicular tubular clusters (VTCs). However, all of the SNAREs were found on both COPII- and COPI-coated membranes, indicating that similar SNARE machinery directs both vesicle pathways. rsec22b and rbet1 do not appear beyond the first Golgi cisterna, whereas syntaxin 5 and membrin penetrate deeply into the Golgi stacks. Temperature shifts reveal that membrin, rsec22b, rbet1, and syntaxin 5 are present together on membranes that rapidly recycle between peripheral and Golgi-centric locations. GOS-28, on the other hand, maintains a fixed localization in the Golgi. By immunoprecipitation analysis, syntaxin 5 exists in at least two major subcomplexes: one containing syntaxin 5 (34-kD isoform) and GOS-28, and another containing syntaxin 5 (41- and 34-kD isoforms), membrin, rsec22b, and rbet1. Both subcomplexes appear to involve direct interactions of each SNARE with syntaxin 5. Our results indicate a central role for complexes among rbet1, rsec22b, membrin, and syntaxin 5 (34 and 41 kD) at two membrane fusion interfaces: the fusion of ER-derived vesicles with VTCs, and the assembly of VTCs to form cis-Golgi elements. The 34-kD syntaxin 5 isoform, membrin, and GOS-28 may function in intraGolgi transport.

    View details for Web of Science ID 000074605300002

    View details for PubMedID 9647643

  • Protein interactions regulating vesicle transport between the endoplasmic reticulum and Golgi apparatus in mammalian cells CELL Hay, J. C., Chao, D. S., Kuo, C. S., Scheller, R. H. 1997; 89 (1): 149-158

    Abstract

    The proposed cis-Golgi vesicle receptor syntaxin 5 was found in a complex with Golgi-associated SNARE of 28 kDa (GOS-28), rbet1, rsly1, and two novel proteins characterized herein: rat sec22b and membrin, both cytoplasmically oriented integral membrane proteins. The complex appears to recapitulate vesicle docking interactions of proteins originating from distinct compartments, since syntaxin 5, rbet1, and GOS-28 localize to Golgi membranes, whereas mouse sec22b and membrin accumulate in the endoplasmic reticulum. Protein interactions in the complex are dramatically rearranged by N-ethylmaleimide-sensitive factor. The complex consists of two or more subcomplexes with some members (rat sec22b and syntaxin 5) in common and others (rbet1 and GOS-28) mutually exclusively associated. We propose that these protein interactions determine vesicle docking/fusion fidelity between the endoplasmic reticulum and Golgi.

    View details for Web of Science ID A1997WR68500018

    View details for PubMedID 9094723