{"id":2282,"date":"2023-02-09T11:55:20","date_gmt":"2023-02-09T16:55:20","guid":{"rendered":"https:\/\/www.med.unc.edu\/medicine\/okudalab\/?page_id=2282"},"modified":"2023-04-05T10:02:34","modified_gmt":"2023-04-05T14:02:34","slug":"research","status":"publish","type":"page","link":"https:\/\/www.med.unc.edu\/medicine\/okudalab\/research\/","title":{"rendered":"Research"},"content":{"rendered":"<p>We inhale about 10,000 L of air to take oxygen into our bodies every day. Along with the inhaled air, numerous pathogens, chemical pollutants, and other irritants are inhaled, which could pose potential life-threatening risks to our lungs. However, our lungs are protected by mucociliary clearance (MCC), a critical innate defense mechanism that is important for maintaining lung health. The Okuda lab\u2019s overall research interest focuses on how the MCC system is regulated to maintain homeostasis in the lung and how it fails in muco-obstructive lung diseases, including cystic fibrosis (CF), asthma, and COPD. Our previous work successfully characterized the regional expression patterns of major airway secretory mucins, MUC5AC\/MUC5B, and CFTR\/ionocytes in normal and CF human airways (<em>Am J Respir Crit Care Med<\/em>, 2019, 2021). These investigations provide insight into the small airway region (&lt; 2 mm in diameter) as a critical site for pathogenesis of muco-obstructive lung diseases. We have developed a microdissection technique for human small airways and established <em>in vitro<\/em> and explant small airway epithelial cell cultures. We have combined these culture systems with single-cell-based omics approaches and gene editing technologies to understand cellular biology and physiology of the human small airways. In response to the emergent situation caused by the SARS-CoV-2 pandemic, the Okuda lab has also\u00a0been actively involved in COVID-19 research.<\/p>\n<figure id=\"attachment_2355\" class=\"thumbnail wp-caption alignleft\" style=\"width: 510px\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-2355\" src=\"https:\/\/www.med.unc.edu\/medicine\/okudalab\/wp-content\/uploads\/sites\/1355\/2023\/02\/Figure-Okuda-pg-300x250.jpg\" alt=\"MUC5AC, MUC5B, and CCSP mRNA co-expression is region-specific in normal human airways\" width=\"500\" height=\"417\" srcset=\"https:\/\/www.med.unc.edu\/medicine\/okudalab\/wp-content\/uploads\/sites\/1355\/2023\/02\/Figure-Okuda-pg-300x250.jpg 300w, https:\/\/www.med.unc.edu\/medicine\/okudalab\/wp-content\/uploads\/sites\/1355\/2023\/02\/Figure-Okuda-pg-1024x854.jpg 1024w, https:\/\/www.med.unc.edu\/medicine\/okudalab\/wp-content\/uploads\/sites\/1355\/2023\/02\/Figure-Okuda-pg-768x640.jpg 768w, https:\/\/www.med.unc.edu\/medicine\/okudalab\/wp-content\/uploads\/sites\/1355\/2023\/02\/Figure-Okuda-pg-600x500.jpg 600w, https:\/\/www.med.unc.edu\/medicine\/okudalab\/wp-content\/uploads\/sites\/1355\/2023\/02\/Figure-Okuda-pg.jpg 1233w\" sizes=\"auto, (max-width: 500px) 100vw, 500px\" \/><figcaption class=\"caption wp-caption-text\"><strong><em>MUC5AC, MUC5B<\/em>, and <em>CCSP<\/em> mRNA co-expression is region-specific in normal human airways.<\/strong> Submucosal glands (SMG) express <em>MUC5B<\/em>, but not <em>MUC5AC<\/em> (<strong>A<\/strong>). Both <em>MUC5B<\/em> and <em>MUC5AC<\/em> are colocalized in <em>CCSP<sup>+<\/sup><\/em> cells in proximal superficial epithelium (<strong>B<\/strong>), whereas <em>MUC5B<\/em> is colocalized in <em>CCSP<sup>+<\/sup><\/em> cells of distal airway superficial epithelia (<strong>C<\/strong>). In the terminal bronchioles, neither <em>MUC5B<\/em> nor <em>MUC5AC<\/em> was detected (<strong>D<\/strong>). (Okuda et al, <em>Am J Respir Crit Care Med, <\/em>2019).<\/figcaption><\/figure>\n<figure id=\"attachment_2351\" class=\"thumbnail wp-caption alignleft\" style=\"width: 510px\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-2351\" src=\"https:\/\/www.med.unc.edu\/medicine\/okudalab\/wp-content\/uploads\/sites\/1355\/2023\/02\/CFTR-Fig-300x163.jpg\" alt=\"CFTR expression in freshly excised normal human large and small airway epithelial cells by RNA-ISH\" width=\"500\" height=\"272\" srcset=\"https:\/\/www.med.unc.edu\/medicine\/okudalab\/wp-content\/uploads\/sites\/1355\/2023\/02\/CFTR-Fig-300x163.jpg 300w, https:\/\/www.med.unc.edu\/medicine\/okudalab\/wp-content\/uploads\/sites\/1355\/2023\/02\/CFTR-Fig-1024x557.jpg 1024w, https:\/\/www.med.unc.edu\/medicine\/okudalab\/wp-content\/uploads\/sites\/1355\/2023\/02\/CFTR-Fig-768x417.jpg 768w, https:\/\/www.med.unc.edu\/medicine\/okudalab\/wp-content\/uploads\/sites\/1355\/2023\/02\/CFTR-Fig-600x326.jpg 600w, https:\/\/www.med.unc.edu\/medicine\/okudalab\/wp-content\/uploads\/sites\/1355\/2023\/02\/CFTR-Fig.jpg 1196w\" sizes=\"auto, (max-width: 500px) 100vw, 500px\" \/><figcaption class=\"caption wp-caption-text\"><strong><em>CFTR<\/em> expression in freshly excised normal human large and small airway epithelial cells by RNA-ISH.<\/strong> RNA-ISH colocalizes <em>CFTR<\/em> in a <em>FOXI1+<\/em> (ionocyte) cell in the large airway (arrow) and <em>SCGB1A1+<\/em> (secretory) cells in the small airway (arrow heads), but not in <em>FOXJ1+<\/em> (ciliated) cells in either region. Scale bars = 10 \u03bcm. (Okuda et al, <em>Am J Respir Crit Care Med<\/em>, 2021).<\/figcaption><\/figure>\n<figure id=\"attachment_2356\" class=\"thumbnail wp-caption alignleft\" style=\"width: 610px\"><img loading=\"lazy\" decoding=\"async\" class=\"wp-image-2356\" src=\"https:\/\/www.med.unc.edu\/medicine\/okudalab\/wp-content\/uploads\/sites\/1355\/2023\/02\/Epithelial-Cell-Cultures-Fig-PDF-300x96.jpg\" alt=\"Epithelial Cell Cultures Figure\" width=\"600\" height=\"191\" srcset=\"https:\/\/www.med.unc.edu\/medicine\/okudalab\/wp-content\/uploads\/sites\/1355\/2023\/02\/Epithelial-Cell-Cultures-Fig-PDF-300x96.jpg 300w, https:\/\/www.med.unc.edu\/medicine\/okudalab\/wp-content\/uploads\/sites\/1355\/2023\/02\/Epithelial-Cell-Cultures-Fig-PDF-1024x327.jpg 1024w, https:\/\/www.med.unc.edu\/medicine\/okudalab\/wp-content\/uploads\/sites\/1355\/2023\/02\/Epithelial-Cell-Cultures-Fig-PDF-768x245.jpg 768w, https:\/\/www.med.unc.edu\/medicine\/okudalab\/wp-content\/uploads\/sites\/1355\/2023\/02\/Epithelial-Cell-Cultures-Fig-PDF-1536x490.jpg 1536w, https:\/\/www.med.unc.edu\/medicine\/okudalab\/wp-content\/uploads\/sites\/1355\/2023\/02\/Epithelial-Cell-Cultures-Fig-PDF-2048x654.jpg 2048w, https:\/\/www.med.unc.edu\/medicine\/okudalab\/wp-content\/uploads\/sites\/1355\/2023\/02\/Epithelial-Cell-Cultures-Fig-PDF-600x191.jpg 600w\" sizes=\"auto, (max-width: 600px) 100vw, 600px\" \/><figcaption class=\"caption wp-caption-text\"><strong><em>In vitro<\/em> human large and small airway epithelial cell cultures.<\/strong> A. Large and small airway epithelial (LAE and SAE, respectively) cells were isolated, expanded, and then cultured in air-liquid interface (ALI) condition. B. H&amp;E staining of well-differentiated <em>in vitro<\/em> LAE and SAE cells at ALI day 28. Scale bars = 10 \u03bcm. (C) Heat map displaying differentially expressed genes (adjusted P value &lt; 0.01, Log FC \u2267 1 or \u2266 -1) between <em>in vitro<\/em> LAE and SAE cells as determined by bulk RNA-seq. (Okuda et al, <em>Am J Respir Crit Care Med<\/em>, 2021).<\/figcaption><\/figure>\n","protected":false},"excerpt":{"rendered":"<p>We inhale about 10,000 L of air to take oxygen into our bodies every day. Along with the inhaled air, numerous pathogens, chemical pollutants, and other irritants are inhaled, which could pose potential life-threatening risks to our lungs. However, our lungs are protected by mucociliary clearance (MCC), a critical innate defense mechanism that is important &hellip; <a href=\"https:\/\/www.med.unc.edu\/medicine\/okudalab\/research\/\" aria-label=\"Read more about Research\">Read more<\/a><\/p>\n","protected":false},"author":81095,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"class_list":["post-2282","page","type-page","status-publish","hentry","odd"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Research - Okuda Lab<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.med.unc.edu\/medicine\/okudalab\/research\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Research - Okuda Lab\" \/>\n<meta property=\"og:description\" content=\"We inhale about 10,000 L of air to take oxygen into our bodies every day. Along with the inhaled air, numerous pathogens, chemical pollutants, and other irritants are inhaled, which could pose potential life-threatening risks to our lungs. 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