{"id":69,"date":"2015-09-16T18:45:00","date_gmt":"2015-09-16T22:45:00","guid":{"rendered":"https:\/\/med.sites.unc.edu\/cfpulmcenter\/core-facilities\/pre-clinical-core\/"},"modified":"2025-03-21T17:16:10","modified_gmt":"2025-03-21T21:16:10","slug":"pre-clinical-core","status":"publish","type":"page","link":"https:\/\/www.med.unc.edu\/marsicolunginstitute\/core-facilities\/pre-clinical-core\/","title":{"rendered":"The Cystic Fibrosis Molecular\/Functional Measurement Core"},"content":{"rendered":"

<\/p>\n

<\/p>\n

<\/p>\n

Director: Martina Gentzsch, Ph.D.
\nCo-Director: Wanda O\u2019Neal, Ph.D.<\/p>\n\n\n\n\n
\"Diagram<\/th>\n<\/tr>\n
\n
The Cystic Fibrosis Molecular\/Functional Measurement<\/em>\u00a0Core<\/i> is designed to provide services to analyze the\u00a0efficacy of treatments that target different stages in the pathogenic\u00a0sequelae of CF disease development.<\/div>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

To support urgently required translational Cystic Fibrosis (CF) research, the Cystic Fibrosis Molecular\/Functional Measurement\u00a0Core<\/strong> of the University of North Carolina CF Research and Translation Core Center is pursuing the following objectives:<\/p>\n

    \n
  1. Evaluation of pre-clinical drug candidates in vitro<\/i><\/strong> in primary human airway and intestinal planar epithelial CF cultures by measurement of ion transport, CFTR maturation and surface expression, drug pharmacokinetics, and airway surface liquid properties. <\/span><\/li>\n
  2. E<\/b>valuation of pre-clinical drug candidates <\/b>ex vivo<\/i><\/b> in organoid models (i.e. colonospheres, nasospheres, and bronchospheres) and various epithelial tissues (mouse distal colon, jejunum, gallbladder, trachea, bronchi, nasopharnyx, and human rectal biopsies). Services provided are quantitative organoid swelling assays, functional assessment of ion transport in tissues, and biochemical assessment of CFTR rescue in organoids and tissues.<\/li>\n
  3. E<\/b>valuation of pre-clinical drug candidates <\/b>in vivo<\/i><\/b> in relevant mouse models of CF and other lung diseases using a variety of assays to determine the efficacy of therapeutic treatments on ion transport defects, CFTR processing, defective mucus clearance, chronic infection, and inflammation. Services provided in this objective include mouse maintenance and distribution, pharmacological treatments, pharmacokinetic analyses, and phenotyping including collection of bronchoalveolar lavage, measurements of soluble mediators, airway mucus burden and clearance, nasal potential difference, salivary secretion rates, histopathology, morphometry, microbiology, and technologically advanced airway imaging.<\/li>\n<\/ol>\n
    \"Cartoon,
    Correction and Potentiation of CFTR. A. Correctors promote transfer of mutant CFTR from the ER to the apical membrane, whereas potentiators enhance activity of apical CFTR. B. Trafficking defect of \u2206F508. Confocal immunofluorescence of apical wild-type and intracellular-retained \u2206F508 CFTR (green) expressed as a virally introduced epitope-tagged variant in primary HBE cells. Cilia are stained in red and nuclei in blue. C. Processing defect of \u2206F508 CFTR. Western blot of wild-type CFTR and \u2206F508 detected in primary normal and CF (\u2206F508\/\u2206F508) HBE cells.<\/figcaption><\/figure>\n

    While certain assays and models provided by the Core focus on restoration of CFTR function in CF, most of our services have broad applications to multiple research programs seeking therapeutic benefit for CF. These include approaches that utilize small-molecule pharmacological interventions, gene therapy, correction of airway surface liquid hydration and mucus clearance defects, normalization of ion transport, and inflammation\/infection control.<\/p>\n

    The availability of models and assays by the Cystic Fibrosis Molecular\/Functional Measurement<\/strong><\/em>\u00a0Core<\/i><\/b> will provide a translational bridge that will support the rapid transfer of emerging drug candidates from the research laboratory to therapies for CF patients.<\/p>\n

    Cystic Fibrosis Molecular\/Functional Measurement Core<\/em> key investigators:<\/strong><\/h2>\n

    Martina Gentzsch, Ph.D.<\/em>
    \nWanda O’Neal, Ph.D.<\/em>
    \nAlessandra Livraghi-Butrico, Ph.D.<\/em>
    \nBarbara Grubb, Ph.D.<\/em>
    \nCharles Esther, M.D., Ph.D.<\/em>
    \nMichael Chua, Ph.D.<\/em><\/p>\n

    Acknowledgement:<\/strong><\/h2>\n

    Funded by the NIH\/NIDDK (P30 DK065988)<\/p>\n

    Contact Information<\/strong><\/h2>\n

    Martina Gentzsch, Ph.D.
    \nAssociate Professor, Department of Cell Biology and Physiology
    \nDirector, Cystic Fibrosis Molecular\/Functional Measurement Core
    \nDirector, CFTR Functional Analysis Core
    \nMarsico Lung Institute\/Cystic Fibrosis Research Center
    \nThe University of North Carolina
    \n1121 Marsico Hall CB 7248
    \n125 Mason Farm Road
    \nChapel Hill, NC 27599
    \nPhone: (919) 966-7058
    \nFax: (919) 966-5178
    \nE-mail: gentzsch@med.unc.edu<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

    Director: Martina Gentzsch, Ph.D. Co-Director: Wanda O\u2019Neal, Ph.D. The Cystic Fibrosis Molecular\/Functional Measurement\u00a0Core is designed to provide services to analyze the\u00a0efficacy of treatments that target different stages in the pathogenic\u00a0sequelae of CF disease development. To support urgently required translational Cystic Fibrosis (CF) research, the Cystic Fibrosis Molecular\/Functional Measurement\u00a0Core of the University of North Carolina CF … Read more<\/a><\/p>\n","protected":false},"author":80252,"featured_media":0,"parent":62,"menu_order":22,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"layout":"","cellInformation":"","apiCallInformation":"","footnotes":"","_links_to":"","_links_to_target":""},"class_list":["post-69","page","type-page","status-publish","hentry","odd"],"acf":[],"yoast_head":"\nThe Cystic Fibrosis Molecular\/Functional Measurement Core | Marsico Lung Institute<\/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\/marsicolunginstitute\/core-facilities\/pre-clinical-core\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"The Cystic Fibrosis Molecular\/Functional Measurement Core | Marsico Lung Institute\" \/>\n<meta property=\"og:description\" content=\"Director: Martina Gentzsch, Ph.D. Co-Director: Wanda O\u2019Neal, Ph.D. The Cystic Fibrosis Molecular\/Functional Measurement\u00a0Core is designed to provide services to analyze the\u00a0efficacy of treatments that target different stages in the pathogenic\u00a0sequelae of CF disease development. 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