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CF Research Consortia

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CFTR Folding Consortium

The CFTR Folding Consortium is composed of a group of investigators dedicated to understanding the process of CFTR folding and trafficking and developing and distributing reagents (antibodies and protein) and methods to facilitate a practical understanding of:

  1. why disease-associated CFTR mutants misfold; and
  2. how to correct these defects.

Methods and reagents are made available to researchers focused on these two goals. Investigators who utilize these resources are required to provide feedback on their utility and are asked to make available any new, improved reagents or methods they developed from the resources. This work is funded by Cystic Fibrosis Foundation Therapeutics (CFFT).

Consortium Membership

Sponsor Institute
William E. Balch, Ph.D. The Scripps Research Institute
Ineke Braakman, Ph.D. Utrecht University
Jeffrey Brodsky, Ph.D.  University of Pittsburgh
Doug Cyr, Ph.D.  University of North Carolina at Chapel Hill
Raymond Frizzell, Ph.D.  University of Pittsburgh School of Medicine
Gergely Lukacs, M.D., Ph.D.  McGill University
William R. Skach, M.D.  Oregon Health & Science University
Eric J. Sorscher, M.D.  The University of Alabama at Birmingham
Philip J. Thomas, Ph.D.  University of Texas Southwestern
  Medical Center at Dallas

Suggested Reading:

Du K, Lukacs GL. Cooperative assembly and misfolding of CFTR domains in vivo. Mol Biol Cell. 2009 Apr;20(7):1903-15. Epub 2009 Jan 28.PMID: 19176754

Kleizen B, van Vlijmen T, de Jonge HR, Braakman I. Folding of CFTR is predominantly cotranslational. Mol Cell. 2005 Oct 28;20(2):277-87.PMID: 16246729

Nakatsukasa K, Huyer G, Michaelis S, Brodsky JL. Dissecting the ER-associated degradation of a misfolded polytopic membrane protein. Cell. 2008 Jan 11;132(1):101-12.PMID: 18191224

Caohuy H, Jozwik C, Pollard HB. Rescue of DeltaF508-CFTR by the SGK1/Nedd4-2 signaling pathway. J Biol Chem. 2009 Sep 11;284(37):25241-53. Epub 2009 Jul 17.PMID: 19617352

Cebotaru L, Vij N, Ciobanu I, Wright J, Flotte T, Guggino WB. Cystic fibrosis transmembrane regulator missing the first four transmembrane segments increases wild type and DeltaF508 processing. J Biol Chem. 2008 Aug 8;283(32):21926-33. Epub 2008 May 28.PMID: 18508776

Mendoza JL, Schmidt A, Li Q, Nuvaga E, Barrett T, Bridges RJ, Feranchak AP, Brautigam CA, Thomas PJ.  Requirements for efficient correction of ΔF508 CFTR revealed by analyses of evolved sequencesCell. 2012 Jan 20;148(1-2):164-74.PMID:22265409

Peters KW, Okiyoneda T, Balch WE, Braakman I, Brodsky JL, Guggino WB, Penland CM, Pollard HB, Sorscher EJ, Skach WR, Thomas PJ, Lukacs GL, Frizzell RA. CFTR Folding Consortium: methods available for studies of CFTR folding and correction. Methods Mol Biol. 2011;742:335-53.PMID:21547742

Rabeh WM, Bossard F, Xu H, Okiyoneda T, Bagdany M, Mulvihill CM, Du K, di Bernardo S, Liu Y, Konermann L, Roldan A, Lukacs GL. Correction of both NBD1 energetics and domain interface is required to restore ΔF508 CFTR folding and functionCell. 2012 Jan 20;148(1-2):150-63.PMID:22265408

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CFTR 3D Structure Consortium

Elucidating the three-dimensional structure of CFTR will enhance our understanding of the mechanism of CFTR function and thereby provide insight into the effects of mutations that lead to CF. This understanding will be critical to the ultimate goal of finding the means to cure and control CF by enabling structure-based drug discovery efforts.

The CFTR 3D Structure Consortium intends to accelerate efforts to obtain this structural information. The Consortium members work together to expand knowledge of the structure, energetics and mechanism of CFTR function.

The Consortium's goals are to:

  • Obtain high quality protein reagents for full-length CFTR and CFTR structural domains;
  • Characterize the physicochemical properties of CFTR and CFTR structural domains;
  • Obtain high resolution 3D structures of interactions between structural domains of CFTR;
  • Obtain high resolution 3D structures of the full length CFTR protein; and
  • Obtain knowledge of the binding location and energetic/folding consequences of CFTR modulators on CFTR or CFTR domains.

Consortium Membership

Sponsor    Institute 
Christie Brouillette, Ph.D.    University of Alabama at Birmingham
Larry DeLucas, Ph.D.    University of Alabama at Birmingham
Robert Ford, Ph.D.    The University of Manchester
Julie Forman-Kay, Ph.D.    The Hospital for Sick Children
John F. Hunt, Ph.D.    Columbia University
John Kappes, Ph.D.    University of Alabama at Birmingham
John Riordan, Ph.D.    University of North Carolina at Chapel Hill
Hanoch Senderowitz, Ph.D.    Bar Ilan University
Patrick Thibodeau, Ph.D.    University of Pittsburgh
Ina Urbatsch, Ph.D.    Texas Tech University Health Sciences Center

Suggested Reading:

Structural Studies of CFTR

Yang Z, Wang C, Zhou Q, An J, Hildebrandt E, Aleksandrov LA, Kappes JC, DeLucas LJ, Riordan JR, Urbatsch IL, Hunt JF, Brouillette CG. Membrane protein stability can be compromised by detergent interactions with the extramembranous soluble domains. Protein Sci. 2014, Jun; 23(6):769-89.

Pollock N, Cant N, Rimington T, Ford RC. Purification of the cystic fibrosis transmembrane conductance regulator protein expressed in Saccharomyces cerevisiae. J Vis Exp. 2014 May 10;(87).

He L, Aleksandrov AA, An J, Cui L, Yang Z, Brouillette CG, Riordan JR. Restoration of NBD1 Thermal Stability Is Necessary and Sufficient to Correct ∆F508 CFTR Folding and Assembly. J Mol Biol. 2014 Jul 30. pii: S0022-2836.

Cant N, Pollock N, Ford RC. CFTR structure and cystic fibrosis. Int J Biochem Cell Biol. 2014 Jul;52:15-25.

Hildebrandt E, Zhang Q, Cant N, Ding H, Dai Q, Peng L, Fu Y, DeLucas LJ, Ford R, Kappes JC, Urbatsch IL. A survey of detergents for the purification of stable, active human cystic fibrosis transmembrane conductance regulator (CFTR). Biochim Biophys Acta. 2014 Nov;1838(11):2825-37.

Bozoky Z, Krzeminski M, Muhandiram R, Birtley JR, Al-Zahrani A, Thomas PJ, Frizzell RA, Ford RC, Forman-Kay JD. Regulatory R region of the CFTR chloride channel is a dynamic integrator of phospho-dependent intra- and intermolecular interactions. Proc Natl Acad Sci U S A. 2013 Nov 19;110(47):E4427-36.

J.E. Dawson, P. Farber and J.D. Forman-Kay. Allosteric Coupling between the Intracellular Coupling Helix 4 and Regulatory Sites of the First Nucleotide-binding Domain of CFTR. PLoS One, 2013 8(9):e74347.

Hunt JF, Wang C, Ford RC. Cystic fibrosis transmembrane conductance regulator (ABCC7) structure. Cold Spring Harb Perspect Med. 2013 Feb 1;3(2):a009514. doi: 10.1101/cshperspect.a009514. Review.

Hudson, R.; Chong, A.; Protasevich, I.I, Vernon, R.; Noy, E.; Bihler, H.; Li An, J.; Kalid, O.; Sela-Culang, I.; Mense, M.; Senderowitz, H.; Brouillette, C,; Forman-Kay, J.D. Conformational Changes Relevant to Channel Activity and Folding within the first Nucleotide Binding Domain of CFTR. J Biol Chem. 2012, 287, 28480-94.

Noy, E.; Senderowitz, H. Combating cystic fibrosis: in search for CF transmembrane conductance regulator (CFTR) modulators. ChemMedChem 2011, 6, 243-51

Kanelis V, Chong PA, Forman-Kay JD. NMR spectroscopy to study the dynamics and interactions of CFTRMethods Mol Biol. 2011;741:377-403. doi: 10.1007/978-1-61779-117-8_25.

Thibodeau, P.H.; Richardson III, J.M.; Wang, W.; Millen, L.; Watson, J.; Mendoza, J.; Du, K.; Fischman, S.; Senderowitz, H.; Lukacs, G.; Kirk, K.; Thomas, P.J. The cystic fibrosis-causing mutation deltaF508 affects multiple steps in cystic fibrosis transmembrane conductance regulator biogenesis. JBC, 2010 285, 35825-35.

Kalid, O.; Fischman, S.; Mense, M.; Shitrit, A.; Bihler, H.; Ben-Zeev, E.; Schutz, N.; Pedemonte, N.; Thomas, P.J.; Bridges, R.J.; Wetmore, D.R.; Marantz, Y.; Senderowitz, H. Small molecule correctors of F508del-CFTR discovered by structure-based virtual screening. J. Comput. Aided. Mol. Design, 2010, 24, 971-91.

Protasevich I, Yang Z, Atwell S, Zhao X, Emtage S, Wetmore D, Hunt JF, Brouillette CG. Thermal unfolding studies show the disease causing F508del mutation in CFTR thermodynamically destabilizes nucleotide-binding domain 1. Protein Sci. 2010 Oct; 19(10)1917-31. PMID: 20687133.

Wang C, Protasevich I, Yang Z, Seehausen D, Skalak T, Zhao X, Atwell S, Emtage SJ. Integrated biophysical studies implicate partial unfolding of NBD1 of CFTR in the molecular pathogenesis of F508del cystic fibrosis. Protein Sci. 2010 Oct; 19(10):1932-47. PMID: 20687163.

Riordan JR. CFTR function and prospects for therapy. Annu Rev Biochem. 2008; 77:701-26. PMID 18304008

Structures of Related ABC Transporters

Ward AB, Szewczyk P, Grimard V, Lee CW, Martinez L, Doshi R, Caya A, Villaluz M, Pardon E, Cregger C, Swartz DJ, Falson PG, Urbatsch IL, Govaerts C, Steyaert J, Chang G. Structures of P-glycoprotein reveal its conformational flexibility and an epitope on the nucleotide-binding domain. Proc Natl Acad Sci U S A. 2013 Aug 13;110(33):13386-91. PMCID: 23901103

Models of CFTR

Rahman KS, Cui G, Harvey SC, McCarty NA., Modeling the conformational changes underlying channel opening in CFTR. PLoS One. 2013 Sep 27;8(9):e74574.

Dalton J, Kalid O, Schushan M, Ben-Tal N, Villà-Freixa J., New model of cystic fibrosis transmembrane conductance regulator proposes active channel-like conformation. J Chem Inf Model. 2012 Jul 23;52(7):1842-53.

Mornon JP, Lehn P, Callebaut I. Molecular models of the open and closed states of the whole human CFTR protein. Cell Mol Life Sci. 2009 Nov;66(21):3469-86.

Huang SY, Bolser D, Liu HY, Hwang TC, Zou X. Molecular modeling of the heterodimer of human CFTR's nucleotide-binding domains using a protein-protein docking approach. J Mol Graph Model. 2009 Apr;27(7):822-8.

Additional Information:

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Mucocilliary Clearance Consortium

The mission of the Mucociliary Clearance Consortium is to:

  • Improve our understanding of how the airway environment (including airway surface liquid volume, ionic content, and glandular macromolecules) results in abnormal mucus and aberrant mucociliary transport, and determine the limits of CFTR, epithelial sodium channel, and other ion transporter activities required to maintain normal physiology;

  • Examine whether mucin biogenesis and post-translational modification pathways are aberrant in CF, and determine their functional relationship to the ion transport environment; and

  • Develop new preclinical and clinical measures of mucociliary clearance to allow a better understanding of this process, prioritization of therapeutic compounds under development, and evaluation of downstream effects elicited by ion transport modulators.

Consortium Membership

Sponsor   Institute
Steve Ballard, Ph.D.   University of South Alabama
William Bennett, Ph.D.    University of North Carolina at Chapel Hill
Brian Button, Ph.D.    University of North Carolina at Chapel Hill
C. William Davis, Ph.D.  University of North Carolina at Chapel Hill
Scott Donaldson, M.D.    University of North Carolina at Chapel Hill
Camile Ehre, Ph.D.  University of North Carolina at Chapel Hill
Justin Hanes, Ph.D.  Johns Hopkins University School of Medicine
Paul Quinton, Ph.D.  University of California San Diego
  School of Medicine
Steve Rowe, Ph.D.  University of Alabama at Birmingham
David Stoltz, M.D., Ph.D.  University of Iowa
Guillermo Tearney, M.D., Ph.D.    Massachusetts General Hospital
Dave Thornton, Ph.D.  University of Manchester
Jeff Wine, Ph.D.    Stanford University
Mehmet Kesimer, Ph.D.    University of North Carolina at Chapel Hill
Michael Rubenstein, Ph.D.   University of North Carolina at Chapel Hill

Suggested Reading:

Ion Transport, Mucus Secretion and Clearance

Birket SE, Chu KK, Liu L, Houser GH, Diephuis BJ, Wilsterman EJ, Dierksen G, Mazur M, Shastry S, Li Y, Watson JD, Smith AT, Schuster BS, Hanes J, Grizzle WE, Sorscher EJ, Tearney GJ, Rowe SM.  A functional anatomic defect of the cystic fibrosis airwayAm J Respir Crit Care Med. 2014 Aug 15;190(4):421-32. PMID: 25029666

Liu L, Shastry S, Byan-Parker S, Houser G, Chu K, Birket SE, Fernandez CM, Gardecki JA, Grizzle W, Wilsterman EJ, Sorscher EJ, Rowe SM, Tearney GJ.  An Autoregulatory Mechanism Governing Mucociliary Transport is Sensitive to Mucus Load Am J Respir Cell Mol Biol. 2014 Jun 17. PMID:24937762

Jeong JH, Joo NS, Hwang PH, Wine JJ.  Mucociliary clearance and submucosal gland secretion in the ex vivo ferret tracheaAm J Physiol Lung Cell Mol Physiol. 2014 Jul 1;307(1):L83-93. PMID:24793168

Wine JJ, Joo NS, Choi JY, Cho HJ, Krouse ME, Wu JV, Khansaheb M, Irokawa T, Ianowski J, Hanrahan JW, Cuthbert AW, Tran KV.  Measurement of fluid secretion from intact airway submucosal glandsMethods Mol Biol. 2011;742:93-112. PMIS: 21547728

Cooper JL, Quinton PM, Ballard ST.  Mucociliary transport in porcine trachea: differential effects of inhibiting chloride and bicarbonate secretion.  Am J Physiol Lung Cell Mol Physiol. 2013 Feb 1;304(3):L184-90. PMID: 23204069

Hoegger MJ, Fischer AJ, McMenimen JD, Ostedgaard LS, Tucker AJ, Awadalla MA, Moninger TO, Michalski AS, Hoffman EA, Zabner J, Stoltz DA, Welsh MJ.  Cystic fibrosis. Impaired mucus detachment disrupts mucociliary transport in a piglet model of cystic fibrosisScience. 2014 Aug 15;345(6198):818-22. PMID: 25124441

Hoegger MJ, Awadalla M, Namati E, Itani OA, Fischer AJ, Tucker AJ, Adam RJ, McLennan G, Hoffman EA, Stoltz DA, Welsh MJ.  Assessing mucociliary transport of single particles in vivo shows variable speed and preference for the ventral trachea in newborn pigsProc Natl Acad Sci U S A. 2014 Feb 11;111(6):2355-60. PMID: 24474805

Zhang L, Button B, Gabriel SE, Burkett S, Yan Y, Skiadopoulos MH, Dang YL, Vogel LN, McKay T, Mengos A, Boucher RC, Collins PL, Pickles RJ. CFTR delivery to 25% of surface epithelial cells restores normal rates of mucus transport to human cystic fibrosis airway epithelium. PLoS Biol. 2009 Jul;7(7):e1000155. Epub 2009 Jul 21.PMID: 19621064

Ballard ST, Parker JC, Hamm CR. Restoration of mucociliary transport in the fluid-depleted trachea by surface-active instillates. Am J Respir Cell Mol Biol. 2006 Apr;34(4):500-4. Epub 2005 Dec 15.PMID: 16357366

Inglis SK, Corboz MR, Ballard ST. Effect of anion secretion inhibitors on mucin content of airway submucosal gland ducts. Am J Physiol. 1998 May;274(5 Pt 1):L762-6.PMID: 9612291

Joo NS, Wine JJ, Cuthbert AW. Lubiprostone stimulates secretion from tracheal submucosal glands of sheep, pigs, and humans. Am J Physiol Lung Cell Mol Physiol. 2009 May;296(5):L811-24. Epub 2009 Feb 20.PMID: 19233902

Choi JY, Khansaheb M, Joo NS, Krouse ME, Robbins RC, Weill D, Wine JJ. Substance P stimulates human airway submucosal gland secretion mainly via a CFTR-dependent process. J Clin Invest. 2009 May;119(5):1189-200. doi: 10.1172/JCI37284. Epub 2009 Apr 20.PMID: 19381016

Ianowski JP, Choi JY, Wine JJ, Hanrahan JW. Substance P stimulates CFTR-dependent fluid secretion by mouse tracheal submucosal glands. Pflugers Arch. 2008 Nov;457(2):529-37. Epub 2008 May 29.PMID: 18509672

Wu JV, Krouse ME, Wine JJ. Acinar origin of CFTR-dependent airway submucosal gland fluid secretion. Am J Physiol Lung Cell Mol Physiol. 2007 Jan;292(1):L304-11. Epub 2006 Sep 22.PMID: 16997881

Garcia MA, Yang N, Quinton PM. Normal mouse intestinal mucus release requires cystic fibrosis transmembrane regulator-dependent bicarbonate secretion. J Clin Invest. 2009 Sep;119(9):2613-22. doi: 10.1172/JCI38662. Epub 2009 Aug 24. Erratum in: J Clin Invest. 2009 Nov;119(11):3497. PMID: 19726884

Mucus and Mucins

Henderson AG, Ehre C, Button B, Abdullah LH, Cai LH, Leigh MW, DeMaria GC, Matsui H, Donaldson SH, Davis CW, Sheehan JK, Boucher RC, Kesimer M.  Cystic fibrosis airway secretions exhibit mucin hyperconcentration and increased osmotic pressureJ Clin Invest. 2014 Jul 1;124(7):3047-60. PMID: 24892808

Ridley C, Kouvatsos N, Raynal BD, Howard M, Collins RF, Desseyn JL, Jowitt TA, Baldock C, Davis CW, Hardingham TE, Thornton DJ.  Assembly of the Respiratory Mucin MUC5B: A NEW MODEL FOR A GEL-FORMING MUCINJ Biol Chem. 2014 Jun 6;289(23):16409-20.  PMID: 24778189

Kesimer M, Ehre C, Burns KA, Davis CW, Sheehan JK, Pickles RJ.  Molecular organization of the mucins and glycocalyx underlying mucus transport over mucosal surfaces of the airways.  Mucosal Immunol. 2013 Mar;6(2):379-92. PMID: 22929560

Button B, Cai LH, Ehre C, Kesimer M, Hill DB, Sheehan JK, Boucher RC, Rubinstein M.  A periciliary brush promotes the lung health by separating the mucus layer from airway epithelia.  Science. 2012 Aug 24;337(6097):937-41. PMID: 22923574

Ensign LM, Henning A, Schneider CS, Maisel K, Wang YY, Porosoff MD, Cone R, Hanes J.  Ex vivo characterization of particle transport in mucus secretions coating freshly excised mucosal tissues.  Mol Pharm. 2013 Jun 3;10(6):2176-82. PMID: 23617606

Schuster BS, Suk JS, Woodworth GF, Hanes J.  Nanoparticle diffusion in respiratory mucus from humans without lung diseaseBiomaterials. 2013 Apr;34(13):3439-46. PMID: 23384790

Kesimer M, Makhov AM, Griffith JD, Verdugo P, Sheehan JK. Unpacking a gel-forming mucin: a view of MUC5B organization after granular release. Am J Physiol Lung Cell Mol Physiol. 2010 Jan;298(1):L15-22. Epub 2009 Sep 25.PMID: 19783639

Kesimer M, Sheehan JK. Analyzing the functions of large glycoconjugates through the dissipative properties of their absorbed layers using the gel-forming mucin MUC5B as an example. Glycobiology. 2008 Jun;18(6):463-72. Epub 2008 Mar 13.PMID: 18339669

Sheehan JK, Kesimer M, Pickles R. Innate immunity and mucus structure and function. Novartis Found Symp. 2006;279:155-66; discussion 167-9, 216-9. Review.PMID: 17278393

Zhu Y, Ehre C, Abdullah LH, Sheehan JK, Roy M, Evans CM, Dickey BF, Davis CW. Munc13-2-/- baseline secretion defect reveals source of oligomeric mucins in mouse airways. J Physiol. 2008 Apr 1;586(7):1977-92. Epub 2008 Feb 7.PMID: 18258655

Davis CW, Dickey BF. Regulated airway goblet cell mucin secretion. Annu Rev Physiol. 2008;70:487-512. Review.PMID: 17988208

Kirkham S, Kolsum U, Rousseau K, Singh D, Vestbo J, Thornton DJ. MUC5B is the major mucin in the gel phase of sputum in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2008 Nov 15;178(10):1033-9. Epub 2008 Sep 5.PMID: 18776153

Thornton DJ, Rousseau K, McGuckin MA. Structure and function of the polymeric mucins in airways mucus. Annu Rev Physiol. 2008;70:459-86. Review.PMID: 17850213

Novel Techniques and Protocols

Shikata H, McLennan G, Hoffman EA, Sonka M. Segmentation of Pulmonary Vascular Trees from Thoracic 3D CT Images. Int J Biomed Imaging. 2009;2009:636240. Epub 2009 Dec 14.PMID: 20052391

Li B, Christensen GE, Hoffman EA, McLennan G, Reinhardt JM. Pulmonary CT image registration and warping for tracking tissue deformation during the respiratory cycle through 3D consistent image registration. Med Phys. 2008 Dec;35(12):5575-83.PMID: 19175115

Tang BC, Dawson M, Lai SK, Wang YY, Suk JS, Yang M, Zeitlin P, Boyle MP, Fu J, Hanes J. Biodegradable polymer nanoparticles that rapidly penetrate the human mucus barrier. Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19268-73. Epub 2009 Nov 9.PMID: 19901335

Suk JS, Lai SK, Wang YY, Ensign LM, Zeitlin PL, Boyle MP, Hanes J. The penetration of fresh undiluted sputum expectorated by cystic fibrosis patients by non-adhesive polymer nanoparticles. Biomaterials. 2009 May;30(13):2591-7. Epub 2009 Jan 26.PMID: 19176245

Lai SK, Wang YY, Wirtz D, Hanes J. Micro- and macrorheology of mucus. Adv Drug Deliv Rev. 2009 Feb 27;61(2):86-100. Epub 2009 Jan 3. Review.PMID: 19166889

Donaldson SH, Corcoran TE, Laube BL, Bennett WD. Mucociliary clearance as an outcome measure for cystic fibrosis clinical research. Proc Am Thorac Soc. 2007 Aug 1;4(4):399-405. Review.PMID: 17652507

Donaldson SH, Bennett WD, Zeman KL, Knowles MR, Tarran R, Boucher RC. Mucus clearance and lung function in cystic fibrosis with hypertonic saline. N Engl J Med. 2006 Jan 19;354(3):241-50.PMID: 16421365

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CF Biomarker Consortium 

The mission of the CF Biomarker Consortium is to identify and validate CF biomarkers to advance research and improve clinical care for individuals with CF. The focus of the Biomarker Consortium is in the areas of identifying biomarkers that:

  • Track and predict disease progression (including early lung disease, lung function decline, and pulmonary exacerbations);
  • Detect improved function of CFTR for new candidate targets and pathways for CF; and
  • Validate preclinical animal model systems.

Consortium Membership

Member Institute
John P. Clancy, M.D.    Cincinnati Children's Hospital Medical Center
Scott Sagel, M.D.  University of Colorado Health Sciences Center
Assem G. Ziady, Ph.D.   Emory University
Marianne Muhlebach, M.D.  University of North Carolina at Chapel Hill
Thomas Kelley, Ph.D.  Case Western Reserve University
Joe Pilewski, M.D.  University of Pittsburgh
Sonya Heltshe, Ph.D. University of Washington and
  Seattle Children’s Research Institute
Nicole Hamblett, Ph.D.  University of Washington and
  Seattle Children’s Research Institute
Steve Rowe, M.D.    University of Alabama at Birmingham

Suggested Reading:

Rowe SM, Heltshe SL, Gonska T, Donaldson SH, Borowitz D, Gelfond D, Sagel SD, Khan U, Mayer-Hamblett N, Van Dalfsen JM, Joseloff E, Ramsey BW; GOAL Investigators of the Cystic Fibrosis Foundation Therapeutics Development Network. Clinical mechanism of the cystic fibrosis transmembrane conductance regulator potentiator ivacaftor in G551D-mediated cystic fibrosis. Am J Respir Crit Care Med. 2014 Jul 15;190(2):175-84.

Heltshe SL, Rowe SM, Mayer-Hamblett N.  Evaluating the predictive ability of sweat chlorideJ Cyst Fibros. 2014 Jan;13(1):118.

Locke LW, Myerburg MM, Markovetz MR, Parker RS, Weber L, Czachowski MR, Harding TJ, Brown SL, Nero JA, Pilewski JM, Corcoran TE. Quantitative imaging of airway liquid absorption in cystic fibrosisEur Respir J. 2014 Sep;44(3):675-84.

Accurso FJ, Van Goor F, Zha J, Stone AJ, Dong Q, Ordonez CL, Rowe SM, Clancy JP, Konstan MW, Hoch HE, Heltshe SL, Ramsey BW, Campbell PW, Ashlock MA. Sweat chloride as a biomarker of CFTR activity: proof of concept and ivacaftor clinical trial data. J Cyst Fibros. 2014 Mar;13(2):139-47.

Joseloff E, Sha W, Bell SC, Wetmore DR, Lawton KA, Milburn MV, Ryals JA, Guo L, Muhlebach MS. Serum metabolomics indicate altered cellular energy metabolism in children with cystic fibrosis.  Pediatr Pulmonol. 2014 May;49(5):463-72.

Rowe SM, Liu B, Hill A, Hathorne H, Cohen M, Beamer JR, Accurso FJ, Dong Q, Ordoñez CL, Stone AJ, Olson ER, Clancy JP; VX06-770-101 Study Group. Optimizing nasal potential difference analysis for CFTR modulator development: assessment of ivacaftor in CF subjects with the G551D-CFTR mutation. PLoS One. 2013 Jul 26;8(7):e66955.

Clancy JP, Szczesniak RD, Ashlock MA, Ernst SE, Fan L, Hornick DB, Karp PH, Khan U, Lymp J, Ostmann AJ, Rezayat A, Starner TD, Sugandha SP, Sun H, Quinney N, Donaldson SH, Rowe SM, Gabriel SE.  Multicenter intestinal current measurements in rectal biopsies from CF and non-CF subjects to monitor CFTR function. PLoS One. 2013 Sep 10;8(9):e73905.

Heltshe SL, Mayer-Hamblett N, Rowe SM.  Understanding the relationship between sweat chloride and lung function in cystic fibrosis Chest. 2013 Oct;144(4):1418.

Corcoran TE, Thomas KM, Brown S, Myerburg MM, Locke LW, Pilewski JM.  Liquid hyper-absorption as a cause of increased DTPA clearance in the cystic fibrosis airway.  EJNMMI Res. 2013 Feb 27;3(1):14.

Moss RB, Mistry SJ, Konstan MW, Pilewski JM, Kerem E, Tal-Singer R, Lazaar AL; CF2110399 Investigators.  Safety and early treatment effects of the CXCR2 antagonist SB-656933 in patients with cystic fibrosis. J Cyst Fibros. 2013 May;12(3):241-8.

De Boeck K, Kent L, Davies J, Derichs N, Amaral M, Rowe SM, Middleton P, de Jonge H, Bronsveld I, Wilschanski M, Melotti P, Danner-Boucher I, Boerner S, Fajac I, Southern K, de Nooijer RA, Bot A, de Rijke Y, de Wachter E, Leal T, Vermeulen F, Hug MJ, Rault G, Nguyen-Khoa T, Barreto C, Proesmans M, Sermet-Gaudelus I; European Cystic Fibrosis Society Clinical Trial Network Standardisation Committee.  CFTR biomarkers: time for promotion to surrogate end-point. Eur Respir J. 2013 Jan;41(1):203-16

Rowe SM, Borowitz DS, Burns JL, Clancy JP, Donaldson SH, Retsch-Bogart G, Sagel SD, Ramsey BW. Progress in cystic fibrosis and the CF Therapeutics Development Network. Thorax. 2012 Oct;67(10):882-90.

Sagel SD, Wagner BD, Anthony MM, Emmett P, Zemanick ET. Sputum biomarkers of inflammation and lung function decline in children with cystic fibrosis. Am J Respir Crit Care Med. 2012 Nov 1;186(9):857-65.

Ratjen F, Saiman L, Mayer-Hamblett N, Lands LC, Kloster M, Thompson V, Emmett P, Marshall B, Accurso F, Sagel S, Anstead M. Effect of azithromycin on systemic markers of inflammation in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa. Chest. 2012 Nov;142(5):1259-66.

Ashlock MA, Olson ER. Therapeutics development for cystic fibrosis: a successful model for a multisystem genetic disease. Annu Rev Med. 2011 Feb 18;62:107-25.

Hug MJ, Derichs N, Bronsveld I, Clancy JP. Measurement of ion transport function in rectal biopsies. Methods Mol Biol. 2011;741:87-107.

Rowe SM, Clancy JP, Wilschanski M. Nasal potential difference measurements to assess CFTR ion channel activity. Methods Mol Biol. 2011;741:69-86.

Zemanick ET, Sagel SD, Harris JK. The airway microbiome in cystic fibrosis and implications for treatment. Curr Opin Pediatr. 2011 Jun;23(3):319-24.

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CFFT Therapeutics Development Network Standard Operating Procedures

CFFT TDN Standard operating procedures (SOPs) relevant to study conduct are generally provided as needed at study startup with other study materials. Since minor variations to these SOPs may be made on a study-by-study basis, the generic versions are not posted here to avoid any confusion over inconsistencies with study-specific versions. However, SOPs on procedures commonly used in clinical studies may be provided to individuals upon request as needed for purposes of protocol development or other general reference needs.

The following SOPs are available* from the TDN Coordinating Center. Please contact us at TDNCC@seattlechildrens.org for more information.

502 - NPD Measurement  – Stripchart and Perfusion Probe
503 - Spirometry
504 - Training and Qualification for Infant PFT Testing
506 - Qualification of NPD Operators
507 - Sputum Induction (DeVilbiss nebulizer)
508 - Sputum Processing for Cytology and Inflammatory Markers
510 - Qualification Standards for Sputum Processing Technicians
514 - Sweat Testing using the Macroduct® 
515 - Training and Qualification to use the Macroduct®
516 - Sweat Testing Analysis
517 - Sputum Induction (Nouvag nebulizer with aquapak)
522 - Preschool Spirometry using Koko Spirometer
523 - Training and Qualification to use the Koko Spirometer
524 - Preschool Forced Oscillation Technique using Cosmed Quark i2m
525 - Training and Qualification to use Cosmed Quark i2m Forced Oscillometer
526 - Preschool Respiratory Inductive Plethysmography using Vivometrics LifeShirt System
527 - Training and Qualification to use Vivometrics LifeShirt System
528 - NPD Measurement – EDC and Perfusion or Perfusion-Free Probe
529 - TDN Qualification Standards for NPD Operators using EDC
530 - Sputum Induction (Nouvag Ultrasonic 2000 Nebulizer with Medication Cup)
531 - Measuring Infant Length
532 - Measuring Infant Head Circumference
533 - Measuring Infant Weight
534 - Sputum Processing (Mechanical) for Cytology and Inflammatory Markers
535 - Sputum Induction (Nouvag Ultraneb Nebulizer)

* List of available SOPs is subject to change without notice.

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Updated 03/02/15

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