Specialty Areas:
Molecular Genetics, Cystic Fibrosis
Research Focus:
I received my PhD in 1993 from Baylor College of Medicine in the Department of Human and Molecular Genetics under the direction of Dr. Arthur Beaudet. During my first year at Baylor, the cystic fibrosis (CF) gene was discovered, and my career path was set. Under Dr. Beaudet’s direction, I was one of the first to report a population-based study on what turned out to be the most common cystic fibrosis mutation, F508del (1). Baylor College of Medicine was also one of the first institutions to make broad use of recombination in embryonic stem cells for generating mouse lines, and for the bulk of my graduate thesis, in collaboration with Dr. Allen Bradley’s group, I was one of several investigators worldwide who successfully generated mice carrying CF gene mutations (2-4). After graduating, I spent the next five years completing a post-doctoral fellowship, again with Dr. Beaudet, evaluating the potential to utilize adenoviral-based vectors for gene transfer in CF (5-10). While the use of adenoviral vectors in clinical trials for gene transfer have not advanced, the experiences at Baylor provided a solid and broad training in molecular biology, human genetics, mouse transgenics and phenotyping, and viral vector use, all of which prepared me for my academic career.
In 1998, I joined the University of North Carolina Cystic Fibrosis Center (now the Marsico Lung Institute/UNC CF Center) as director of the Molecular Biology and Mouse Core, a position that I still hold. It has been a huge honor to serve in this position. The Molecular Biology and Mouse Core provides the molecular biology (DNA cloning, RNA isolation and analysis, gene editing (CRISPR/Cas9) service), mouse model production, mouse model genotyping and phenotyping for collaborating scientists at UNC and outside investigators as needed. Since 1998, the Core has consistently contributed to the overall group by providing needed expertise, reagents, and equipment in molecular biology and mouse colony management. The Molecular Biology and Mouse Core has been, and continues to be, supported by the NHLBI, NIDDK, Cystic Fibrosis Foundation through a variety of mechanisms related to large collaborative efforts, including PPG Core Grant funding, the NIDDK-supported MTCC and CFRTCC, and the CFF Research and Development Program (RDP).
Throughout its history, the Molecular Biology Core has sought to keep up with the ever-present technological advances. Over the years, not only has the Core conducted standard cloning, PCR, RNA analysis, we have worked with investigators to develop expertise in gene expression microarrays, RNAsequencing, siRNA technologies, CRISPR/Cas9, and now are providing RNA in situ hybridization via the RNAScope technology and single-cell RNA analyses services. The success of the Core is highlighted by the broad range of publications supported by the Core (See bibliography; provide my Bibliography link) and the large number of grants that have utilized Core services to generate key preliminary data to ensure the success of the project. Continued funding by the granting agencies for services provided by is also a measure of the Core’s productivity. The services provided by the Core are also now and integral and important aspect of the work provided by SPIROVATION (http://www.spirovation.com/).
In addition to providing Core services, Dr. O’Neal also has had the ability to pursue independent lines of research in collaboration with Marsico Lung Institute scientists. Particularly rewarding are the research efforts focused on understanding the gene modifiers that associate with CF phenotypes (11-16), expanding the utility of theScnn1b-Tg mouse model for muco-obstructive lung disease (17-25); see Mouse Core for more information), and the understanding of mucin biology and genetics (26-30). While Dr. O’Neal’s true passion is CF research (http://news.unchealthcare.org/news/2015/april/the-family-disease), the environment in the Marsico Lung Institute has allowed her to apply her skills and expertise to a variety of related problems, including general airway cell biology and physiology and chronic obstructive pulmonary disease, primarily though involvement in the SPIROMICS study (31-33)(http://www.spirovation.com/), where she serves as Chair of the Biomarkers Working Group, and the PreCISE asthma network, where she serves as Chair of Biomarkers and Quality Control.
In the UNC Health Care and School of Medicine Newsroom, the article entitled: “The Family Disease” was published in April, 2015, and describes Dr. O’Neal’s path to research. Later, in 2018, UNC Health produced a video, “The Family Disease: Insights into CF Research,” which serves as an accompaniment to the 2015 article.
Selected Bibliography:
- Plender EG, Prodanov T, Hsieh P, Nizamis E, Harvey WT, Sulovari A, Munson KM, Kaufman EJ, O’Neal WK, Valdmanis PN, Marschall T, Bloom JD, Eichler EE. Structural and genetic diversity in the secreted mucins MUC5AC and MUC5B. Am J Hum Genet. 2024 Aug 8;111(8):1700-1716. doi: 10.1016/j.ajhg.2024.06.007. PMID: 38991590.
- Sheridan MB, Aksit MA, Pagel K, Hetrick K, Shultz-Lutwyche H, Myers B, Buckingham KJ, Pace RG, Ling H, Pugh E, O’Neal WK, Bamshad MJ, Gibson RL, Knowles MR, Blackman SM, Cutting GR, Raraigh KS. The clinical utility of sequencing the entirety of CFTR. J Cyst Fibros. 2024 May 10:S1569-1993(24)00062-6. doi: 10.1016/j.jcf.2024.04.018. Epub ahead of print. PMID: 38734509.
- Sun Q, Yang Y, Rosen JD, Chen J, Li X, Guan W, Jiang MZ, Wen J, Pace RG, Blackman SM, Bamshad MJ, Gibson RL, Cutting GR, O’Neal WK, Knowles MR, Kooperberg C, Reiner AP, Raffield LM, Carson AP, Rich SS, Rotter JI, Loos RJF, Kenny E, Jaeger BC, Min YI, Fuchsberger C, Li Y. MagicalRsq-X: A cross-cohort transferable genotype imputation quality metric. Am J Hum Genet. 2024 May 2;111(5):990-995. doi: 10.1016/j.ajhg.2024.04.001.PMID: 38636510. PMCID: PMC11080605.
- Stonebraker JR, Pace RG, Gallins PJ, Dang H, Aksit MA, Faino AV, Gordon WW, MacParland S, Bamshad MJ, Gibson RL, Cutting GR, Durie PR, Wright FA, Zhou YH, Blackman SM, O’Neal WK, Ling SC, Knowles MR. Genetic variation in severe cystic fibrosis liver disease is associated with novel mechanisms for disease pathogenesis. Hepatology. 2024 Mar 27. doi: 10.1097/HEP.0000000000000863. Epub ahead of print. PMID: 38536042.
- Asakura T, Okuda K, Chen G, Dang H, Kato T, Mikami Y, Schworer SA, Gilmore RC, Radicioni G, Hawkins P, Barbosa Cardenas SM, Saito M, Cawley AM, De la Cruz G, Chua M, Alexis NE, Masugi Y, Noone PG, Ribeiro CMP, Kesimer M, Olivier KN, Hasegawa N, Randell SH, O’Neal WK, Boucher RC. Proximal and Distal Bronchioles Contribute to the Pathogenesis of Non-Cystic Fibrosis Bronchiectasis (NCFB). Am J Respir Crit Care Med. 2024 Feb 15;209(4):374-389. doi: 10.1164/rccm.202306-1093OC. PMID: 38016030. PMCID: PMC10878387.
- Ngo D, Pratte KA, Flexeder C, Petersen H, Dang H, Ma Y, Keyes MJ, Gao Y, Deng S, Peterson BD, Farrell LA, Bhambhani VM, Palacios C, Quadir J, Gillenwater L, Xu H, Emson C, Gieger C, Suhre K, Graumann J, Jain D, Conomos MP, Tracy RP, Guo X, Liu Y, Johnson WC, Cornell E, Durda P, Taylor KD, Papanicolaou GJ, Rich SS, Rotter JI, Rennard SI, Curtis JL, Woodruff PG, Comellas AP, Silverman EK, Crapo JD, Larson MG, Vasan RS, Wang TJ, Correa A, Sims M, Wilson JG, Gerszten RE, O’Connor GT, Barr RG, Couper D, Dupuis J, Manichaikul A, O’Neal WK, Tesfaigzi Y, Schulz H, Bowler RP. Systemic Markers of Lung Function and Forced Expiratory Volume in 1 Second Decline across Diverse Cohorts. Ann Am Thorac Soc. 2023 Aug;20(8):1124-1135. doi: 10.1513/AnnalsATS.202210-857OC. PMID: 37351609; PMCID: PMC10405603.
- Izquierdo M, Marion CR, Genese F, Newell JD, O’Neal WK, Li X, Hawkins GA, Barjaktarevic I, Barr RG, Christenson S, Cooper CB, Couper D, Curtis J, Han MK, Hansel NN, Kanner RE, Martinez FJ, Paine R 3rd, Tejwani V, Woodruff PG, Zein JG, Hoffman EA, Peters SP, Meyers DA, Bleecker ER, Ortega VE; National Heart, Lung and Blood Institute’s SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) investigators. Impact of Bronchiectasis on COPD Severity and Alpha-1 Antitrypsin Deficiency as a Risk Factor in Individuals with a Heavy Smoking History. Chronic Obstr Pulm Dis. 2023 Jul 26;10(3):199-210. doi: 10.15326/jcopdf.2022.0388. PMID: 37199731. PMCID: PMC10484491.
- Van Buren E, Radicioni G, Lester S, O’Neal WK, Dang H, Kasela S, Garudadri S, Curtis JL, Han MK, Krishnan JA, Wan ES, Silverman EK, Hastie A, Ortega VE, Lappalainen T, Nawijn MC, Berge MVD, Christenson SA, Li Y, Cho MH, Kesimer M, Kelada SNP. Genetic regulators of sputum mucin concentration and their associations with COPD phenotypes. PLoS Genet. 2023 Jun 23;19(6):e1010445. doi: 10.1371/journal.pgen.1010445. PMID: 37352370; PMCID: PMC10325042.
- Hill AC, Guo C, Litkowski EM, Manichaikul AW, Yu B, Konigsberg IR, Gorbet BA, Lange LA, Pratte KA, Kechris KJ, DeCamp M, Coors M, Ortega VE, Rich SS, Rotter JI, Gerzsten RE, Clish CB, Curtis JL, Hu X, Obeidat ME, Morris M, Loureiro J, Ngo D, O’Neal WK, Meyers DA, Bleecker ER, Hobbs BD, Cho MH, Banaei-Kashani F, Bowler RP. Large scale proteomic studies create novel privacy considerations. Sci Rep. 2023 Jun 7;13(1):9254. doi: 10.1038/s41598-023-34866-6. PMID: 37286633; PMCID: PMC10247808.
- Mikami Y, Grubb BR, Rogers TD, Dang H, Asakura T, Kota P, Gilmore RC, Okuda K, Morton LC, Sun L, Chen G, Wykoff JA, Ehre C, Vilar J, van Heusden C, Livraghi-Butrico A, Gentzsch M, Button B, Stutts MJ, Randell SH, O’Neal WK, Boucher RC. Chronic airway epithelial hypoxia exacerbates injury in muco-obstructive lung disease through mucus hyperconcentration. Sci Transl Med. 2023 Jun 7;15(699):eabo7728. doi: 10.1126/scitranslmed.abo7728. PMID: 37285404. PMCID: PMC10664029.
- DiLillo KM, Norman KC, Freeman CM, Christenson SA, Alexis NE, Anderson WH, Barjaktarevic IZ, Barr RG, Comellas AP, Bleecker ER, Boucher RC, Couper DJ, Criner GJ, Doerschuk CM, Wells JM, Han MK, Hoffman EA, Hansel NN, Hastie AT, Kaner RJ, Krishnan JA, Labaki WW, Martinez FJ, Meyers DA, O’Neal WK, Ortega VE, Paine R 3rd, Peters SP, Woodruff PG, Cooper CB, Bowler RP, Curtis JL, Arnold KB; SPIROMICS investigators. A blood and bronchoalveolar lavage protein signature of rapid FEV1 decline in smoking-associated COPD. Sci Rep. 2023 May 22;13(1):8228. doi: 10.1038/s41598-023-32216-0. PMID: 37217548; PMCID: PMC10203309.
- Zhou YH, Gallins PJ, Pace RG, Dang H, Aksit MA, Blue EE, Buckingham KJ, Collaco JM, Faino AV, Gordon WW, Hetrick KN, Ling H, Liu W, Onchiri FM, Pagel K, Pugh EW, Raraigh KS, Rosenfeld M, Sun Q, Wen J, Li Y, Corvol H, Strug LJ, Bamshad MJ, Blackman SM, Cutting GR, Gibson RL, O’Neal WK, Wright FA, Knowles MR. Genetic Modifiers of Cystic Fibrosis Lung Disease Severity: Whole Genome Analysis of 7,840 Patients. Am J Respir Crit Care Med. 2023 May 15;207(10):1324-1333. doi: 10.1164/rccm.202209-1653OC. PMID: 36921087.
- LaFon DC, Woo H, Fedarko N, Azar A, Hill H, Tebo AE, Martins TB, Han MK, Krishnan JA, Ortega VE, Barjaktarevic I, Kaner RJ, Hastie A, O’Neal WK, Couper D, Woodruff PG, Curtis JL, Hansel NN, Nahm MH, Dransfield MT, Putcha N; SPIROMICS investigators. Reduced quantity and function of pneumococcal antibodies are associated with exacerbations of COPD in SPIROMICS. Clin Immunol. 2023 May;250:109324. doi: 10.1016/j.clim.2023.109324. PMID: 37030524. PMCID: PMC10171244.
- LeMaster WB, Quibrera PM, Couper D, Tashkin DP, Bleecker ER, Doerschuk CM, Ortega VE, Cooper C, Han MK, Woodruff PG, O’Neal WK, Anderson WH, Alexis NE, Bowler RP, Barr RG, Kaner RJ, Dransfield MT, Paine R 3rd, Kim V, Curtis JL, Martinez FJ, Hastie AT, Barjaktarevic I. Clinical Implications of Low Absolute Blood Eosinophil Count in the SPIROMICS COPD Cohort. Chest. 2023 Mar;163(3):515-528. doi: 10.1016/j.chest.2022.10.029. PMID: 36343688; PMCID: PMC10083128.
- Esther CR Jr, O’Neal WK, Alexis NE, Koch AL, Cooper CB, Barjaktarevic I, Raffield LM, Bowler RP, Comellas AP, Peters SP, Hastie AT, Curtis JL, Ronish B, Ortega VE, Wells JM, Halper-Stromberg E, Rennard SI, Boucher RC. Prolonged, Physiologically Relevant Nicotine Concentrations in the Airways of Smokers. Am J Physiol Lung Cell Mol Physiol. 2023 Jan 1;324(1):L32-L37. doi: 10.1152/ajplung.00038.2022. PMID: 36342131. PMCID: PMC9829458.
- Kato T, Asakura T, Edwards CE, Dang H, Mikami Y, Okuda K, Chen G, Sun L, Gilmore RC, Hawkins P, De la Cruz G, Cooley MR, Bailey AB, Hewitt SM, Chertow DS, Borczuk AC, Salvatore S, Martinez FJ, Thorne LB, Askin FB, Ehre C, Randell SH, O’Neal WK, Baric RS, Boucher RC; NIH COVID-19 Autopsy Consortium. Prevalence and mechanisms of mucus accumulation in COVID-19 lung disease. Am J Respir Crit Care Med. 2022 Dec 1;206(11):1336-1352. doi: 10.1164/rccm.202111-2606OC. PMID: 35816430. PMCID: PMC9746856.
- Dinnon KH§, Leist SR§, Okuda K§, Dang H§, Fritch EJ§, Gully KL, De la Cruz G, Evangelista MD, Asakura T, Gilmore RC, Hawkins P, Nakano S, West A, Schäfer A, Gralinski LE, Everman JL, Sajuthi SP, Zweigart MR, Dong S, McBride J, Cooley MR, Hines JB, Love MK, Groshong SD, VanSchoiack A, Phelan SJ, Liang Y, Hether T, Leon M, Zumwalt RE, Barton LM, Duval EJ, Mukhopadhyay S, Stroberg E, Borczuk A, Thorne LB, Sakthivel MK, Lee YZ, Hagood JS, Mock JR, Seibold MA, O’Neal WK, Montgomery SA, Boucher RC*, Baric RS*. SARS-CoV-2 infection produces chronic pulmonary epithelial and immune cell dysfunction with fibrosis in mice. Sci Transl Med. 2022 Sep 28;14(664):eabo5070. doi: 10.1126/scitranslmed.abo5070. PMID: 35857635. PMCID: PMC9273046. §These authors contributed equally. *Joint senior authorship.
- Biering SB, Sarnik SA, Wang E, Zengel JR, Leist SR, Schäfer A, Sathyan V, Hawkins P, Okuda K, Tau C, Jangid AR, Duffy CV, Wei J, Gilmore RC, Alfajaro MM, Strine MS, Nguyenla X, Van Dis E, Catamura C, Yamashiro LH, Belk JA, Begeman A, Stark JC, Shon DJ, Fox DM, Ezzatpour S, Huang E, Olegario N, Rustagi A, Volmer AS, Livraghi-Butrico A, Wehri E, Behringer RR, Cheon DJ, Schaletzky J, Aguilar HC, Puschnik AS, Button B, Pinsky BA, Blish CA, Baric RS, O’Neal WK, Bertozzi CR, Wilen CB, Boucher RC, Carette JE, Stanley SA, Harris E, Konermann S, Hsu PD. Genome-wide bidirectional CRISPR screens identify mucins as host factors modulating SARS-CoV-2 infection. Nat Genet. 2022 Aug;54(8):1078-1089. doi: 10.1038/s41588-022-01131-x. PMID: 35879412. PMCID: PMC9355872.
- Esther CR Jr, O’Neal WK, Anderson WH, Kesimer M, Ceppe A, Doerschuk CM, Alexis NE, Hastie AT, Barr RG, Bowler RP, Wells JM, Oelsner EC, Comellas AP, Tesfaigzi Y, Kim V, Paulin LM, Cooper CB, Han MK, Huang YJ, Labaki WW, Curtis JL, Boucher RC; SPIROMICS. Identification of Sputum Biomarkers Predictive of Pulmonary Exacerbations in Chronic Obstructive Pulmonary Disease. Chest. 2022 May;161(5):1239-1249. doi: 10.1016/j.chest.2021.10.049. PMID: 34801592. PMCID: PMC9131049.
- Morrison CB, Edwards CE, Shaffer KM, Araba KC, Wykoff JA, Williams DR, Asakura T, Dang H, Morton LC, Gilmore RC, O’Neal WK, Boucher RC, Baric RS, Ehre C. SARS-CoV-2 infection of airway cells causes intense viral and cell shedding, two spreading mechanisms affected by IL-13. Proc Natl Acad Sci U S A. 2022 Apr 19;119(16):e2119680119. doi: 10.1073/pnas.2119680119. PMID: 35353667. PMCID: PMC9169748.
- Kato T, Radicioni G, Papanikolas MJ, Stoychev GV, Markovetz MR, Aoki K, Porterfield M, Okuda K, Barbosa Cardenas SM, Gilmore RC, Morrison CB, Ehre C, Burns KA, White KK, Brennan TA, Goodell HP, Thacker H, Loznev HT, Forsberg LJ, Nagase T, Rubinstein M, Randell SH, Tiemeyer M, Hill DB, Kesimer M, O’Neal WK, Ballard ST, Freeman R, Button B, Boucher RC. Mucus concentration-dependent biophysical abnormalities unify submucosal gland and superficial airway dysfunction in cystic fibrosis. Sci Adv. 2022 Apr;8(13):eabm9718. doi: 10.1126/sciadv.abm9718. PMID: 35363522.
- Morrison CB, Shaffer KM, Araba KC, Markovetz MR, Wykoff JA, Quinney NL, Hao S, Delion MF, Flen AL, Morton LC, Liao J, Hill DB, Drumm ML, O’Neal WK, Kesimer M, Gentzsch M, Ehre C. Treatment of cystic fibrosis airway cells with CFTR modulators reverses aberrant mucus properties via hydration. Eur Respir J. 2022 Feb 3;59(2):2100185. doi: 10.1183/13993003.00185-2021. PMID: 34172469. PMCID: PMC8859811.
- Georas SN, Wright RJ, Ivanova A, Israel E, LaVange LM, Akuthota P, Carr TF, Denlinger LC, Fajt ML, Kumar R, O’Neal WK, Phipatanakul W, Szefler SJ, Aronica MA, Bacharier LB, Burbank AJ, Castro M, Alexander LC, Bamdad J, Cardet JC, Comhair SAA, Covar RA, DiMango EA, Erwin K, Erzurum SC, Fahy JV, Gaffin JM, Gaston B, Gerald LB, Hoffman EA, Holguin F, Jackson DJ, James J, Jarjour NN, Kenyon NJ, Khatri S, Kirwan JP, Kraft M, Krishnan JA, Liu AH, Liu MC, Marquis MA, Martinez F, Mey J, Moore WC, Moy JN, Ortega VE, Peden DB, Pennington E, Peters MC, Ross K, Sanchez M, Smith LJ, Sorkness RL, Wechsler ME, Wenzel SE, White SR, Zein J, Zeki AA, Noel P; PrecISE Study Team. The Precision Interventions for Severe and/or Exacerbation-Prone (PrecISE) Asthma Network: an overview of Network organization, procedures and interventions. J Allergy Clin Immunol. 2022 Feb;149(2):488-516.e9. doi: 10.1016/j.jaci.2021.10.035. PMID: 34848210. PMCID: PMC8821377.
- Sun Q, Liu W, Rosen JD, Huang L, Pace RG, Dang H, Gallins PJ, Blue EE, Ling H, Corvol H, Strug LJ, Bamshad MJ, Gibson RL, Pugh EW, Blackman SM, Cutting GR, O’Neal WK, Zhou YH, Wright FA, Knowles MR, Wen J, Li Y; Cystic Fibrosis Genome Project. Leveraging TOPMed imputation server and constructing a cohort-specific imputation reference panel to enhance genotype imputation among cystic fibrosis patients. HGG Adv. 2022 Jan 11;3(2):100090. doi: 10.1016/j.xhgg.2022.100090. PMID: 35128485; PMCID: PMC8804187.
- Radicioni G, Ceppe A, Ford AA, Alexis NE, Barr RG, Bleecker ER, Christenson SA, Cooper CB, Han MK, Hansel NN, Hastie AT, Hoffman EA, Kanner RE, Martinez FJ, Ozkan E, Paine R 3rd, Woodruff PG, O’Neal WK, Boucher RC, Kesimer M. Airway mucin MUC5AC and MUC5B concentrations and the initiation and progression of chronic obstructive pulmonary disease: an analysis of the SPIROMICS cohort. Lancet Respir Med. 2021 Nov;9(11):1241-1254. doi: 10.1016/S2213-2600(21)00079-5. PMID: 34058148. PMCID: PMC8570975.
- Carpenter J, Wang Y, Gupta R, Li Y, Haridass P, Subramani DB, Reidel B, Morton L, Ridley C, O’Neal WK, Buisine MP, Ehre C, Thornton DJ, Kesimer M. Assembly and organization of the N-terminal region of mucin MUC5AC: Indications for structural and functional distinction from MUC5B. Proc Natl Acad Sci U S A. 2021 Sep 28;118(39):e2104490118. doi: 10.1073/pnas.2104490118. PMID: 34548396; PMCID: PMC8488587.
- Eastman AC, Pace RG, Dang H, Aksit MA, Vecchio-Pagán B, Lam AN, O’Neal WK, Blackman SM, Knowles MR, Cutting GR. SLC26A9 SNP rs7512462 is not associated with lung disease severity or lung function response to ivacaftor in cystic fibrosis patients with G551D-CFTR. J Cyst Fibros. 2021 Sep;20(5):851-856. doi: 10.1016/j.jcf.2021.02.007. PMID: 33674211. PMCID: PMC8410892.
- Fortis S, Comellas A, Bhatt SP, Hoffman EA, Han MK, Bhakta NR, Paine R 3rd, Ronish B, Kanner RE, Dransfield M, Hoesterey D, Buhr RG, Barr RG, Dolezal B, Ortega VE, Drummond MB, Arjomandi M, Kaner RJ, Kim V, Curtis JL, Bowler RP, Martinez F, Labaki WW, Cooper CB, O’Neal WK, Criner G, Hansel NN, Krishnan JA, Woodruff P, Couper D, Tashkin D, Barjaktarevic I. Ratio of Forced Expiratory Volume in 1 second /Slow Vital Capacity (FEV1/SVC)<0.7 is associated with clinical, functional, and radiologic features of obstructive lung disease in smokers with preserved lung function. Chest. 2021 Jul;160(1):94-103. doi: 10.1016/j.chest.2021.01.067. PMID: 33539837. PMCID: PMC8295909.
- Okuda K, Dang H, Kobayashi Y, Carraro G, Nakano S, Chen G, Kato T, Asakura T, Gilmore RC, Morton LC, Lee RE, Mascenik T, Yin WN, Barbosa Cardenas SM, O’Neal YK, Minnick CE, Chua M, Quinney NL, Gentzsch M, Anderson CW, Ghio A, Matsui H, Nagase T, Ostrowski LE, Grubb BR, Olsen JC, Randell SH, Stripp BR, Tata PR, O’Neal WK, Boucher RC. Secretory Cells Dominate Airway CFTR Expression and Function in Human Airway Superficial Epithelia. Am J Respir Crit Care Med. 2021 May 15;203(10):1275-1289. doi: 10.1164/rccm.202008-3198OC. PMID: 33321047. PMCID: PMC8456462.
- Israel E, Denlinger LC, Bacharier LB, LaVange LM, Moore WC, Peters MC, Georas SN, Wright RJ, Mauger DT, Noel P, Akuthota P, Bach J, Bleecker ER, Cardet JC, Carr TF, Castro M, Cinelli A, Comhair SAA, Covar RA, Alexander LC, DiMango EA, Erzurum SC, Fahy JV, Fajt ML, Gaston BM, Hoffman EA, Holguin F, Jackson DJ, Jain S, Jarjour NN, Ji Y, Kenyon NJ, Kosorok MR, Kraft M, Krishnan JA, Kumar R, Liu AH, Liu MC, Ly NP, Marquis MA, Martinez FD, Moy JN, O’Neal WK, Ortega VE, Peden DB, Phipatanakul W, Ross K, Smith LJ, Szefler SJ, Teague WG, Tulchinsky AF, Vijayanand P, Wechsler ME, Wenzel SE, White SR, Zeki AA, Ivanova A. PrecISE: Precision Medicine in Severe Asthma: An adaptive platform trial with biomarker ascertainment. J Allergy Clin Immunol. 2021 May;147(5):1594-1601. doi: 10.1016/j.jaci.2021.01.037. PMID: 33667479. PMCID: PMC8113113.
- Pratte KA, Curtis JL, Kechris K, Couper D, Cho MH, Silverman EK, DeMeo DL, Sciurba FC, Zhang Y, Ortega VE, O’Neal WK, Gillenwater LA, Lynch DA, Hoffman EA, Newell JD Jr, Comellas AP, Castaldi PJ, Miller BE, Pouwels SD, Hacken NHTT, Bischoff R, Klont F, Woodruff PG, Paine R, Barr RG, Hoidal J, Doerschuk CM, Charbonnier JP, Sung R, Locantore N, Yonchuk JG, Jacobson S, Tal-Singer R, Merrill D, Bowler RP. Soluble receptor for advanced glycation end products (sRAGE) as a biomarker of COPD. Respir Res. 2021 Apr 27;22(1):127. doi: 10.1186/s12931-021-01686-z. PMID: 33906653; PMCID: PMC8076883.
- Dunican EM, Elicker BM, Henry T, Gierada DS, Schiebler ML, Anderson W, Barjaktarevic I, Barr RG, Bleecker ER, Boucher RC, Bowler RP, Christenson SA, Comellas A, Cooper CB, Couper D, Criner GJ, Dransfield M, Doerschuk CM, Drummond MB, Hansel NN, Han MK, Hastie AT, Hoffman EA, Krishnan JA, Lazarus SC, Martinez FJ, McCulloch CE, O’Neal WK, Ortega VE, Paine R 3rd, Peters S, Schroeder JD, Woodruff PG, Fahy JV. Mucus Plugs and Emphysema in the Pathophysiology of Airflow Obstruction and Hypoxemia in Smokers. Am J Respir Crit Care Med. 2021 Apr 15;203(8):957-968. doi: 10.1164/rccm.202006-2248OC. PMID: 33180550. PMCID: PMC8048745.
- Opron K, Begley LA, Erb-Downward JR, Freeman C, Madapoosi S, Alexis NE, Barjaktarevic I, Graham Barr R, Bleecker ER, Bowler RP, Christenson SA, Comellas AP, Cooper CB, Couper DJ, Doerschuk CM, Dransfield MT, Han MK, Hansel NN, Hastie AT, Hoffman EA, Kaner RJ, Krishnan J, O’Neal WK, Ortega VE, Paine R 3rd, Peters SP, Michael Wells J, Woodruff PG, Martinez FJ, Curtis JL, Huffnagle GB, Huang YJ. Lung microbiota associations with clinical features of COPD in the SPIROMICS cohort. NPJ Biofilms Microbiomes. 2021 Feb 5;7(1):14. doi: 10.1038/s41522-021-00185-9. PMID: 33547327. PMCID: PMC7865064.
- Xu J, Livraghi-Butrico A, Hou X, Rajagopalan C, Zhang J, Song J, Jiang H, Wei HG, Wang H, Bouhamdan M, Ruan J, Yang D, Qiu Y, Youming X, Barrett RP, McClellan SA, Mou H, Wu Q, Chen X, Rogers TD, Wilkinson KJ, Gilmore RC, Esther CR Jr, Zaman K, Liang X, Sobolic M, Hazlett L, Zhang K, Frizzell RA, Gentzsch M, O’Neal WK, Grubb BR, Chen YE, Boucher RC, Sun F. Phenotypes of CF rabbits generated by CRISPR/Cas9-mediated disruption of the CFTR gene. JCI Insight. 2021 Jan 11;6(1):e139813. doi: 10.1172/jci.insight.139813. PMID: 33232302. PMCID: PMC7821608.
- Gillenwater LA, Pratte KA, Hobbs BD, Cho MH, Zhuang Y, Halper-Stromberg E, Cruickshank-Quinn C, Reisdorph N, Petrache I, Labaki WW, O’Neal WK, Ortega VE, Jones DP, Uppal K, Jacobson S, Michelotti G, Wendt CH, Kechris KJ, Bowler RP. Plasma Metabolomic Signatures of Chronic Obstructive Pulmonary Disease and the Impact of Genetic Variants on Phenotype-Driven Modules. Netw Syst Med. 2020 Dec 1;3(1):159-181. doi: 10.1089/nsm.2020.0009. PMID: 33987620; PMCID: PMC8109053.
- Putcha N, Fawzy A, Matsui EC, Liu MC, Bowler RP, Woodruff PG, O’Neal WK, Comellas AP, Han MK, Dransfield MT, Wells JM, Lugogo N, Gao L, Talbot CC 2nd, Hoffman EA, Cooper CB, Paulin LM, Kanner RE, Criner G, Ortega VE, Barr RG, Krishnan JA, Martinez FJ, Drummond MB, Wise RA, Diette GB, Hersh CP, Hansel NN. Clinical Phenotypes of Atopy and Asthma in COPD: A Meta-analysis of SPIROMICS and COPDGene. Chest. 2020 Dec;158(6):2333-2345. doi: 10.1016/j.chest.2020.04.069. PMID: 32450244. PMCID: PMC7768932.
- Dang H, Polineni D, Pace RG, Stonebraker JR, Corvol H, Cutting GR, Drumm ML, Strug LJ, O’Neal WK, Knowles MR. Mining GWAS and eQTL data for CF lung disease modifiers by gene expression imputation. PLoS One. 2020 Nov 30;15(11):e0239189. doi: 10.1371/journal.pone.0239189. PMID: 33253230. PMCID: PMC7703903.
- Kim V, Jeong S, Zhao H, Kesimer M, Boucher RC, Wells JM, Christenson SA, Han MK, Dransfield M, Paine R 3rd, Cooper CB, Barjaktarevic I, Bowler R, Curtis JL, Kaner RJ, O’Beirne SL, O’Neal WK, Rennard SI, Martinez FJ, Woodruff PG. Current smoking with or without chronic bronchitis is independently associated with goblet cell hyperplasia in healthy smokers and COPD subjects. Sci Rep. 2020 Nov 18;10(1):20133. doi: 10.1038/s41598-020-77229-1. PMID: 33208859; PMCID: PMC7674445.
- Mock JR, Dial CF, Tune MK, Gilmore RC, O’Neal WK, Dang H, Doerschuk CM. Impact of Regulatory T Cells on Type 2 Alveolar Epithelial Cell Transcriptomes during Resolution of Acute Lung Injury and Contributions of IFN-γ. Am J Respir Cell Mol Biol. 2020 Oct;63(4):464-477. doi: 10.1165/rcmb.2019-0399OC. PMID: 32543909. PMCID: PMC7528916.
- Kato T, Hiraishi Y, Kaseda K, Suzuki S, Tanaka G, Yamauchi Y, Yasui M, Shinozaki-Ushiku A, Ushiku T, Yamaji O, O’Neal WK, Nagase T. A 79-Year-Old Man With Progressive Dyspnea and Multiple Pulmonary Nodules. Chest. 2020 Aug;158(2):e79-e84. doi: 10.1016/j.chest.2020.03.067. PMID: 32768080.
- Hou YJ, Okuda K, Edwards CE, Martinez DR, Asakura T, Dinnon III KH, Kato T, Lee RE, Yount BL, Mascenik TM, Chen G, Olivier KN, Ghio A, Tse LV, Leist SR, Gralinski LE, Schäfer A, Dang H, Gilmore R, Fulcher L, Livraghi-Butrico A, Nicely NI, Cameron M, Cameron C, Kelvin DJ, de Silva A, Margolis DM, Markmann A, Bartelt L, Zumwalt R, Martinez FJ, Salvatore SP, Borczuk A, Tata PR, Sontake V, Kimple A, Jaspers I, O’Neal WK, Randell SH, Boucher RC, Baric RS. SARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract. Cell. 2020 Jul 23;182(2):429-446.e14. doi: 10.1016/j.cell.2020.05.042. PMID: 32526206; PMCID: PMC7250779.
- Zhang WZ, Oromendia C, Kikkers SA, Butler JJ, O’Beirne S, Kim K, O’Neal WK, Freeman CM, Christenson SA, Peters SP, Wells JM, Doerschuk C, Putcha N, Barjaktarevic I, Woodruff PG, Cooper CB, Bowler RP, Comellas AP, Criner GJ, Paine R 3rd, Hansel NN, Han MK, Crystal RG, Kaner RJ, Ballman KV, Curtis JL, Martinez FJ, Cloonan SM. Increased airway iron parameters and risk for exacerbation in COPD: an analysis from SPIROMICS. Sci Rep. 2020 Jun 29;10(1):10562. doi: 10.1038/s41598-020-67047-w. PMID: 32601308; PMCID: PMC7324559.
- Raffield LM, Dang H, Pratte KA, Jacobson S, Gillenwater LA, Ampleford E, Barjaktarevic I, Basta P, Clish CB, Comellas AP, Cornell E, Curtis JL, Doerschuk C, Durda P, Emson C, Freeman CM, Guo X, Hastie AT, Hawkins GA, Herrera J, Johnson WC, Labaki WW, Liu Y, Masters B, Miller M, Ortega VE, Papanicolaou G, Peters S, Taylor KD, Rich SS, Rotter JI, Auer P, Reiner AP, Tracy RP, Ngo D, Gerszten RE, O’Neal WK, Bowler RP; NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium. Comparison of Proteomic Assessment Methods in Multiple Cohort Studies. Proteomics. 2020 Jun;20(12):e1900278. doi: 10.1002/pmic.201900278. PMID: 32386347; PMCID: PMC7425176.
- Rao W, Wang S, Mahalingam R, Duleba M, Xie J, Gollar K, Niroula S, Qi Y, Neupane R, Liew A, Vincent M, Okuda K, O’Neal WK, Boucher RC, Dickey BF, Wechsler ME, Ibrahim O, Engelhardt JF, Crum CP, Mertens TCJ, Wang W, Jyothula SSK, Karmouty-Quintana H, Parekh KR, Metersky ML, McKeon FD, Xian W. Regenerative metaplastic clones in COPD lung drive inflammation and fibrosis. Cell. 2020 May 14;181(4):848-864.e18. doi: 10.1016/j.cell.2020.03.047. PMID: 32298651. PMCID: PMC7294989.
- McCarron A, Cmielewski P, Reyne N, McIntyre C, Finnie J, Craig F, Rout-Pitt N, Delhove J, Schjenken JE, Chan HY, Boog B, Knight E, Gilmore RC, O’Neal WK, Boucher RC, Parsons D, Donnelley M. Phenotypic Characterization and Comparison of Cystic Fibrosis Rat Models Generated Using CRISPR/Cas9 Gene Editing. Am J Pathol. 2020 May;190(5):977-993. doi: 10.1016/j.ajpath.2020.01.009. PMID: 32084371.
- O’Neal WK, Ribeiro CMP. “Shocking the System” to Achieve Efficient Gene Targeting in Primary Human Airway Epithelia. Am J Respir Cell Mol Biol. 2020 Mar;62(3):279-280. doi: 10.1165/rcmb.2019-0360ED. PMID: 31633992. PMCID: PMC7055690.
- Ortega VE, Li X, O’Neal WK, Lackey L, Ampleford E, Hawkins GA, Grayeski PJ, Laederach A, Barjaktarevic I, Barr RG, Cooper C, Couper D, Han MK, Kanner RE, Kleerup EC, Martinez FJ, Paine Iii R, Peters SP, Pirozzi C, Rennard SI, Woodruff PG, Hoffman EA, Meyers DA, Bleecker ER; NHLBI Subpopulations and Intermediate Outcomes Measures in COPD Study (SPIROMICS). The Effects of Rare SERPINA1 Variants on Lung Function and Emphysema in SPIROMICS. Am J Respir Crit Care Med. 2020 Mar 1;201(5):540-554. doi: 10.1164/rccm.201904-0769OC. PMID: 31661293. PMCID: PMC7047460.
- van Heusden C, Button B, Anderson WH, Ceppe A, Morton LC, O’Neal WK, Dang H, Alexis NE, Donaldson SH, Stephan H, Boucher RC, Lazarowski ER. Inhibition of ATP hydrolysis restores airway surface liquid production in cystic fibrosis airway epithelia. Am J Physiol Lung Cell Mol Physiol. 2020 Feb 1;318(2):L356-L365. doi: 10.1152/ajplung.00449.2019. PMID: 31800264. PMCID: PMC7052677.
- Barjaktarevic IZ, Buhr RG, Wang X, Hu S, Couper D, Anderson W, Kanner RE, Paine Iii R, Bhatt SP, Bhakta NR, Arjomandi M, Kaner RJ, Pirozzi CS, Curtis JL, O’Neal WK, Woodruff PG, Han MK, Martinez FJ, Hansel N, Wells JM, Ortega VE, Hoffman EA, Doerschuk CM, Kim V, Dransfield MT, Drummond MB, Bowler R, Criner G, Christenson SA, Ronish B, Peters SP, Krishnan JA, Tashkin DP, Cooper CB; NHLBI SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS). Clinical Significance of Bronchodilator Responsiveness Evaluated by Forced Vital Capacity in COPD: SPIROMICS Cohort Analysis. Int J Chron Obstruct Pulmon Dis. 2019 Dec 20;14:2927-2938. doi: 10.2147/COPD.S220164. PMID: 31908441. PMCID: PMC6930016.
- Hobbs BD, Putman RK, Araki T, Nishino M, Gudmundsson G, Gudnason V, Eiriksdottir G, Zilhao Nogueira NR, Dupuis J, Xu H, O’Connor GT, Manichaikul A, Nguyen J, Podolanczuk AJ, Madahar P, Rotter JI, Lederer DJ, Barr RG, Rich SS, Ampleford EJ, Ortega VE, Peters SP, O’Neal WK, Newell JD Jr, Bleecker ER, Meyers DA, Allen RJ, Oldham JM, Ma SF, Noth I, Jenkins RG, Maher TM, Hubbard RB, Wain LV, Fingerlin TE, Schwartz DA, Washko GR, Rosas IO, Silverman EK, Hatabu H, Cho MH, Hunninghake GM; COPDGene Investigators, ECLIPSE Investigators, SPIROMICS Research Group, and UK ILD Consortium. Overlap of Genetic Risk Between Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med. 2019 Dec 1;200(11):1402-1413. doi: 10.1164/rccm.201903-0511OC. PMID: 31339356. PMCID: PMC6884045.
- Chen G, Sun L, Kato T, Okuda K, Martino MB, Abzhanova A, Lin JM, Gilmore RC, Batson BD, O’Neal YK, Volmer AS, Dang H, Deng Y, Randell SH, Button B, Livraghi-Butrico A, Kesimer M, Ribeiro CM, O’Neal WK, Boucher RC. IL-1β dominates the promucin secretory cytokine profile in cystic fibrosis. J Clin Invest. 2019 Oct 1;129(10):4433-4450. doi: 10.1172/JCI125669. PMID: 31524632. PMCID: PMC6763234.
- Labaki WW, Gu T, Murray S, Curtis JL, Yeomans L, Bowler RP, Barr RG, Comellas AP, Hansel NN, Cooper CB, Barjaktarevic I, Kanner RE, Paine R 3rd, McDonald MN, Krishnan JA, Peters SP, Woodruff PG, O’Neal WK, Diao W, He B, Martinez FJ, Standiford TJ, Stringer KA, Han MK. Serum amino acid concentrations and clinical outcomes in smokers: SPIROMICS metabolomics study. Sci Rep. 2019 Aug 6;9(1):11367. doi: 10.1038/s41598-019-47761-w. PMID: 31388056. PMCID: PMC6684630.
- Halper-Stromberg E, Gillenwater L, Cruickshank-Quinn C, O’Neal WK, Reisdorph N, Petrache I, Zhuang Y, Labaki WW, Curtis JL, Wells J, Rennard S, Pratte KA, Woodruff P, Stringer KA, Kechris K, Bowler RP. Bronchoalveolar Lavage Fluid from COPD Patients Reveals More Compounds Associated with Disease than Matched Plasma. Metabolites. 2019 Jul 25;9(8). doi: 10.3390/metabo9080157. PMID: 31349744; PMCID: PMC6724137.
- Chen G, Ribeiro CMP, Sun L, Okuda K, Kato T, Gilmore RC, Martino MB, Dang H, Abzhanova A, Lin JM, Hull-Ryde EA, Volmer AS, Randell SH, Livraghi-Butrico A, Deng Y, Scherer PE, Stripp BR, O’Neal WK, Boucher RC. XBP1S regulates MUC5B in a promoter variant-dependent pathway in IPF airway epithelia. Am J Respir Crit Care Med. 2019 Jul 15;200(2):220-234. doi: 10.1164/rccm.201810-1972OC. PMID: 30973754; PMCID: PMC6635783.
- Garudadri S, Woodruff PG, Han MK, Curtis JL, Barr RG, Bleecker ER, Bowler RP, Comellas A, Cooper CB, Criner G, Dransfield MT, Hansel NN, Paine R 3rd, Krishnan JA, Peters SP, Hastie AT, Martinez FJ, O’Neal WK, Couper DJ, Alexis NE, Christenson SA. Systemic markers of inflammation in smokers with symptoms despite preserved spirometry in SPIROMICS. Chest. 2019 May;155(5):908-917. doi: 10.1016/j.chest.2018.12.022. PMID: 30684474; PMCID: PMC6533449.
- Okuda K, Chen G, Subramani DB, Wolf M, Gilmore RC, Kato T, Radicioni G, Kesimer M, Chua M, Dang H, Livraghi-Butrico A, Ehre C, Doerschuk CM, Randell SH, Matsui H, Nagase T, O’Neal WK, Boucher RC. Localization of Secretory Mucins MUC5AC and MUC5B in Normal/Healthy Human Airways. Am J Respir Crit Care Med. 2019 Mar 15;199(6):715-727. doi: 10.1164/rccm.201804-0734OC. PMID: 30352166. PMCID: PMC6423099.
- Gong J, Wang F, Xiao B, Panjwani N, Lin F, Keenan K, Avolio J, Esmaeili M, Zhang L, He G, Soave D, Mastromatteo S, Baskurt Z, Kim S, O’Neal WK, Polineni D, Blackman SM, Corvol H, Cutting GR, Drumm M, Knowles MR, Rommens JM, Sun L, Strug LJ. Genetic association and transcriptome integration identify contributing genes and tissues at cystic fibrosis modifier loci. PLoS Genet. 2019 Feb 26;15(2):e1008007. doi: 10.1371/journal.pgen.1008007. PMID: 30807572. PMCID: PMC6407791.
- Christenson SA, van den Berge M, Faiz A, Bhakta N, Bonser LR, Zlockf LT, Junga KL, Barjaktarevic IZ, Barr RG, Bleecker ER, Boucher RC, Bowler RP, Comellas AP, Curtis JL, Han MK, Hansel NN, Hiemstra PS, Kaner RJ, Krishnan JA, Martinez FJ, O’Neal WK, Paine R III, Timens W, Wells JM, Spira A, Erle DJ, Woodruff PG. An airway IL-17A genomic signature identifies a steroid-unresponsive COPD subgroup. J Clin Invest. 2019 Jan 2;129(1):169-181. doi: 10.1172/JCI121087. PMID: 30383540. PMCID: PMC6307967.
- Kesimer M, Smith B, Ceppe A, Anderson WH, O’Neal W, Barr RG, Woodruff PG, Han MK, Hoffman EA, Martinez F, Curtis J, Paine R III, Cooper CB, Ford AA, Bleecker ER, Boucher RC. Mucin concentrations and peripheral airways obstruction in COPD. Am J Respir Crit Care Med. 2018 Dec 1;198(11):1453-1456. doi: 10.1164/rccm.201806-1016LE. PMID: 30130124. PMCID: PMC6290944.
- Ash SY, Harmouche R, Putman RK, Ross JC, Martinez FJ, Choi AM, Bowler RP, Regan EA, Curtis JL, Han MK, Boucher RC, O’Neal W, Hatabu H, Lynch DA, Rosas IO, Hunninghake GM, Estepar RSJ, Washko GR; COPDGene Investigators. Association between acute respiratory disease events and the MUC5B promoter polymorphism in smoker. Thorax. 2018 Nov;73(11):1071-1074. doi: 10.1136/thoraxjnl-2017-211208. PMID: 29440587. PMCID: PMC6089672.
- O’Neal WK, Knowles MR. Cystic fibrosis disease modifiers: Complex genetics defines the phenotypic diversity in a monogenic disease. Annu Rev Gemoics Hum Genetics. 2018 Oct 3;8(1):14744. doi: 10.1038/s41598-018-33053-2. PMID: 29709203.
- Chen G, Volmer AS, Wilkinson KJ, Deng Y, Jones LC, Yu D, Bustamante-Marin XM, Burns KA, Grubb BR, O’Neal WK, Livraghi-Butrico A, Boucher RC. Role of Spdef in the regulation of Muc5b expression in the airways of naïve and muco-obstructed mice. Am J Respir Cell Mol Biol. 2018 Sep;59(3):383-396. doi: 10.1165/rcmb.2017-0127OC. PMID: 29579396. PMCID: PMC6189647.
- Putcha N, Fawzy A, Paul GG, Lambert AA, Psoter KJ, Sidhaye VK, Woo J, Wells JM, Labaki WW, Doerschuk CM, Kanner RE, Han MK, Martinez C, Paulin LM, Martinez FJ, Wise RA, O’Neal WK, Barr RG, Hansel NN; SPIROMICS investigators. Anemia and Adverse Outcomes in a Chronic Obstructive Pulmonary Disease Population with a High Burden of Comorbidities. An Analysis from SPIROMICS. Ann Am Thorac Soc. 2018 Jun;15(6):710-717. doi: 10.1513/AnnalsATS.201708-687OC. PMID: 30726108. PMCID: PMC6207135.
- Putcha N, Paul GG, Azar A, Wise RA, O’Neal WK, Dransfield MT, Woodruff PG, Curtis JL, Comellas AP, Drummond MB, Lambert AA, Paulin LM, Fawzy A, Kanner RE, Paine R 3rd, Han MK, Martinez FJ, Bowler RP, Barr RG, Hansel NN; SPIROMICS investigators. Lower serum IgA is associated with COPD exacerbation risk in SPIROMICS. PLoS One. 2018 Apr 12;13(4):e0194924. doi: 10.1371/journal.pone.0194924. PMID: 29649230. PMCID: PMC5896903.
- Saini Y, Lewis B, Yu D, Dang H, Livraghi-Butrico A, Del Piero F, O’Neal W, Boucher R. Effect of LysM+ macrophage depletion on lung pathology in mice with chronic bronchitis. Physiol Rep. 2018 Apr;6(8):e13677. doi: 10.14814/phy2.13677. PMID: 29667749. PMCID: PMC5904692.
- Burkes RM, Gassett AJ, Ceppe AS, Anderson W, O’Neal WK, Woodruff PG, Krishnan JA, Barr RG, Han MK, Martinez FJ, Comellas AP, Lambert AA, Kaufman JD, Dransfield MT, Wells JM, Kanner RE, Paine R 3rd, Bleecker ER, Paulin LM, Hansel NN, Drummond MB; SPIROMICS Investigators. Rural Residence and COPD Exacerbations: Analysis of the SPIROMICS Cohort. Ann Am Thorac Soc. 2018 Mar 27. doi: 10.1513/AnnalsATS.201710-837OC. PMID: 29584453. PMCID: PMC6207115.
- Livraghi-Butrico A, Wilkinson K, Volmer A, Gilmore R, Rogers T, Caldwell R, Burns K, Esther C Jr., Mall M, Boucher R, O’Neal W, Grubb B. Lung disease phenotypes caused by over-expression of combinations of alpha, beta, and gamma subunits of the epithelial sodium channel in mouse airways. Am J Physiol Lung Cell Mol Physiol. 2018 Feb 1;314(2):L318-L331. doi: 10.1152/ajplung.00382.2017. PMID: 29074490. PMCID: PMC5866504.
- Morris MA, Jacobson SR, Kinney GL, Tashkin DP, Woodruff PG, Hoffman EA, Kanner RE, Cooper CB, Drummond MB, Barr RG, Oelsner EC, Make BJ, Han MK, Hansel NN, O’Neal WK, Bowler RP. Marijuana Use Associations with Pulmonary Symptoms and Function in Tobacco Smokers Enrolled in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS). Chronic Obstr Pulm Dis. 2018 Jan 24;5(1):46-56. doi: 10.15326/jcopdf.5.1.2017.0141. PMID: 29629404. PMCID: PMC5870739.
- Rowson-Hodel AR, Wald JH, Hatakeyama J, O’Neal WK, Stonebraker JR, VanderVorst K, Saldana MJ, Borowsky AD, Sweeney C, Carraway KL 3rd. Membrane Mucin Muc4 promotes blood cell association with tumor cells and mediates efficient metastasis in a mouse model of breast cancer. Oncogene. 2018 Jan 11;37(2):197-207. doi: 10.1038/onc.2017.327. PMID: 28892049. PMCID: PMC5930013.
- Martinez CH, Li SX, Hirzel AJ, Stolberg VR, Alexis NE, Barr RG, Bleecker ER, Carretta EE, Christenson SA, Cooper CB, Couper DJ, Doerschuk CM, Han MK, Hansel NN, Hastie AT, Hoffman EA, Kaner RJ, Martinez FJ, Meyers DA, O’Neal WK, Paine R 3rd, Putcha N, Rennard SI, Woodruff PG, Zeidler M, Curtis JL, Freeman CM; SPIROMICS Investigators. Alveolar eosinophilia in current smokers with chronic obstructive pulmonary disease in the SPIROMICS cohort. J Allergy Clin Immunol. 2018 Jan;141(1):429-432. doi: 10.1016/j.jaci.2017.07.039. PMID: 28916185. PMCID: PMC5758424.
- Bowler RP, Hansel NN, Jacobson S, Graham Barr R, Make BJ, Han MK, O’Neal WK, Oelsner EC, Casaburi R, Barjaktarevic I, Cooper C, Foreman M, Wise RA, DeMeo DL, Silverman EK, Bailey W, Harrington KF, Woodruff PG, Drummond MB; for COPDGene and SPIROMICS Investigators. Electronic Cigarette Use in US Adults at Risk for or with COPD: Analysis from Two Observational Cohorts. J Gen Intern Med. 2017 Dec;32(12):1315-1322. doi: 10.1007/s11606-017-4150-7. PMID: 28884423. PMCID: PMC5698219.
- Hastie AT, Martinez FJ, Curtis JL, Doerschuk CM, Hansel NN, Christenson S, Putcha N, Ortega VE, Li X, Barr RG, Carretta EE, Couper DJ, Cooper CB, Hoffman EA, Kanner RE, Kleerup E, O’Neal WK, Paine R 3rd, Peters SP, Alexis NE, Woodruff PG, Han MK, Meyers DA, Bleecker ER; SPIROMICS investigators. Association of sputum and blood eosinophil concentrations with clinical measures of COPD severity: an analysis of the SPIROMICS cohort. Lancet Respir Med. 2017 Dec;5(12):956-967. doi: 10.1016/S2213-2600(17)30432-0. PMID: 29146301. PMCID: PMC5849066.
- Choi S, Haghighi B, Choi J, Hoffman EA, Comellas AP, Newell JD, Wenzel SE, Castro M, Fain SB, Jarjour NN, Schiebler ML, Barr RG, Han MK, Bleecker ER, Cooper CB, Couper D, Hansel N, Kanner RE, Kazerooni EA, Kleerup EAC, Martinez FJ, O’Neal WK, Woodruff PG, Lin CL. Differentiation of quantitative CT imaging phenotypes in asthma versus COPD. BMJ Open Respir Res. 2017 Nov 9;4(1):e000252. doi: 10.1136/bmjresp-2017-000252. PMID: 29435345. PMCID: PMC5687530.
- Donoghue LJ*, Livraghi-Butrico A*, McFadden KM, Thomas JM, Chen G, Grubb BR, O’Neal WK, Boucher RC, Kelada SNP. Identification of trans protein QTL for secreted airway mucins in mice and a causal role for Bpifb1. Genetics. 2017 Oct;207(2):801-812. doi: 10.1534/genetics.117.300211. PMID: 28851744. PMCID: PMC5629340.
- Anderson WH, Ha JW, Couper DJ, O’Neal WK, Barr RG, Bleecker ER, Carretta EE, Cooper CB, Doerschuk CM, Drummond MB, Han MK, Hansel NN, Kim V, Kleerup EC, Martinez FJ, Rennard SI, Tashkin D, Woodruff PG, Paine R 3rd, Curtis JL, Kanner RE; SPIROMICS Research Group. Variability in objective and subjective measures affects baseline values in studies of patients with COPD. PLoS One. 2017 Sep 21;12(9):e0184606. doi: 10.1371/journal.pone.0184606. PMID: 28934249. PMCID: PMC5608200.
- Kesimer M, Ford AA, Ceppe A, Radicioni G, Cao R, Davis WC, Doerschuk CM, Alexis NE, Anderson WH, Henderson AG, Barr G, Bleecker ER, Christenson SA, Cooper CB, Han MLK, Hansel NN, Hastie AT, Hoffman EA, Kanner RE, Martinez F, Paine R, Woodruff PG, O’Neal WK, Boucher RC. Airway mucin concentration as a marker of chronic bronchitis. N Engl J Med. 2017 Sep 7;377(10):911-922. doi: 10.1056/NEJMoa1701632. PMID: 28877023. PMCID: PMC5706541.
- O’Neal WK. Lung Cell-Specific Cre Deleter Mouse Strains: Going Back to Move Forward. Am J Respir Cell Mol Biol. 2017 Aug;57(2):149-150. doi: 10.1165/rcmb.2017-0099ED. PMID: 28762768.
- Polineni D, Dang H, Jones L, Gallins P, Pace R, Stonebraker J, Commander L, Krenicky J, Zhou Y, Corvol H, Cutting G, Drumm M, Strug L, Boyle M, Durie P, Chmiel J, Zou F, Wright F, O’Neal W, Knowles M. Airway mucosal host defense is key to genomic regulation of cystic fibrosis lung disease severity. Am J Respir Crit Care Med. 2018 Jan 1;197(1):79-93. doi: 10.1164/rccm.201701-0134OC. PMID: 28853905. PMCID: PMC5765386.
- Livraghi-Butrico A, Grubb BR, Wilkinson K, Volmer AS, Burns KA, Evans C, O’Neal WK, Boucher RC. Contribution of mucus concentration and secreted mucins Muc5ac and Muc5b to the pathogenesis of muco-obstructive lung disease. Mucosal Immunol. 2017 Mar;10(2):395-407. doi: 10.1038/mi.2016.63. PMID: 27435107. PMCID: PMC5250616.
- Keene JD, Jacobson S, Kechris K, Kinney GL, Foreman MG, Doerschuk CM, Make BJ, Curtis JL, Rennard SI, Barr RG, Bleecker ER, Kanner RE, Kleerup EC, Hansel NN, Woodruff PG, Han MK, Paine R 3rd, Martinez FJ, Bowler RP, O’Neal WK; COPDGene and SPIROMICS Investigators. Biomarkers Predictive of Exacerbations in the SPIROMICS and COPDGene Cohorts. Am J Respir Crit Care Med. 2017 Feb 15;195(4):473-481. doi: 10.1164/rccm.201607-1330OC. PMID: 27579823. PMCID: PMC5378424.
- Corvol H, Blackman SM, Boelle PY, Gallins PJ, Pace RG, Stonebraker JR, Accurso FJ, Clement A, Collaco JM, Dang H, Dang AT, Franca A, Gong J, Guillot L, Keenan K, Li W, Lin F, Patrone MV, Raraigh KS, Sun L, Zhou YH, O’Neal WK, Sontag MK, Levy H, Durie PR, Rommens JM, Drumm ML, Wright FA, Strug LJ, Cutting GR, Knowles MR. Genome-wide association meta-analysis identifies five modifier loci of lung disease severity in cystic fibrosis. Nat Commun. 2015;6:8382. doi: 10.1038/ncomms9382. PMID: 26417704. PMCID: PMC4589222.
- Freeman CM, Crudgington S, Stolberg VR, Brown JP, Sonstein J, Alexis NE, Doerschuk CM, Basta PV, Carretta EE, Couper DJ, Hastie AT, Kaner RJ, O’Neal WK, Paine R, 3rd, Rennard SI, Shimbo D, Woodruff PG, Zeidler M, Curtis JL. Design of a multi-center immunophenotyping analysis of peripheral blood, sputum and bronchoalveolar lavage fluid in the subpopulations and intermediate outcome measures in COPD study (SPIROMICS). J Transl Med. 2015;13:19. doi: 10.1186/s12967-014-0374-z. PMID: 25622723; PMCID: PMC4314767.
- O’Neal WK, Gallins P, Pace RG, Dang H, Wolf WE, Jones LC, Guo X, Zhou YH, Madar V, Huang J, Liang L, Moffatt MF, Cutting GR, Drumm ML, Rommens JM, Strug LJ, Sun W, Stonebraker JR, Wright FA, Knowles MR. Gene expression in transformed lymphocytes reveals variation in endomembrane and HLA pathways modifying cystic fibrosis pulmonary phenotypes. Am J Hum Genet. 2015 Feb 5;96(2):318-28. doi: 10.1016/j.ajhg.2014.12.022. PMID: 25640674; PMCID: PMC4320265.
- Saini Y, Wilkinson KJ, Terrell KA, Burns KA, Livraghi-Butrico A, Doerschuk CM, O’Neal WK, Boucher RC. Neonatal pulmonary macrophage depletion coupled to defective mucus clearance increases susceptibility to pneumonia and alters pulmonary immune responses. Am J Respir Cell Mol Biol. 2016 Feb;54(2):210-21. doi: 10.1165/rcmb.2014-0111OC. PMID: 26121027; PMCID: PMC4821038.
- Guo X, Pace RG, Stonebraker JR, O’Neal WK, Knowles MR. Meconium ileus in cystic fibrosis is not linked to central repetitive region length variation in MUC1, MUC2, and MUC5AC. J Cyst Fibros. 2014 Dec;13(6):613-6. doi: 10.1016/j.jcf.2014.05.005. PMID: 24920497; PMCID: PMC4253052.
- Guo X, Zheng S, Dang H, Pace RG, Stonebraker JR, Jones CD, Boellmann F, Yuan G, Haridass P, Fedrigo O, Corcoran DL, Seibold MA, Ranade SS, Knowles MR, O’Neal WK, Voynow JA. Genome reference and sequence variation in the large repetitive central exon of human MUC5AC. Am J Respir Cell Mol Biol. 2014 Jan;50(1):223-32. doi: 10.1165/rcmb.2013-0235OC. PMID: 24010879; PMCID: PMC3930937.
- O’Neal WK, Anderson W, Basta PV, Carretta EE, Doerschuk CM, Barr RG, Bleecker ER, Christenson SA, Curtis JL, Han MK, Hansel NN, Kanner RE, Kleerup EC, Martinez FJ, Miller BE, Peters SP, Rennard SI, Scholand MB, Tal-Singer R, Woodruff PG, Couper DJ, Davis SM; SPIROMICS Investigators. Comparison of serum, EDTA plasma and P100 plasma for luminex-based biomarker multiplex assays in patients with chronic obstructive pulmonary disease in the SPIROMICS study. J Transl Med. 2014 Jan 8;12:9. doi: 10.1186/1479-5876-12-9. PMID: 24397870; PMCID: PMC3928911.
- Couper D, LaVange LM, Han M, Barr RG, Bleecker E, Hoffman EA, Kanner R, Kleerup E, Martinez FJ, Woodruff PG, Rennard S. Design of the subpopulations and intermediate outcomes in COPD study. Thorax. 2014 May;69(5):491-4. doi: 10.1136/thoraxjnl-2013-203897. PMID: 24029743; PMCID: PMC3954445.
- Livraghi-Butrico A, Kelly EJ, Wilkinson KJ, Rogers TD, Gilmore RC, Harkema JR, Randell SH, Boucher RC, O’Neal WK, Grubb BR. Loss of Cftr function exacerbates the phenotype of Na(+) hyperabsorption in murine airways. Am J Physiol Lung Cell Mol Physiol. 2013 Apr 1;304(7):L469-80. doi: 10.1152/ajplung.00150.2012. PMID: 23377346; PMCID: PMC3627939.
- Martino MB, Jones L, Brighton B, Ehre C, Abdulah L, Davis CW, Ron D, O’Neal WK, Ribeiro CM. The ER stress transducer IRE1β is required for airway epithelial mucin production. Mucosal Immunol. 2013 May;6(3):639-54. doi: 10.1038/mi.2012.105. PMID: 23168839; PMCID: PMC4031691.
- Roy M, Livraghi-Butrico A, Fletcher AA, McElwee MM, Evans SE, Boerner RM, Alexander SN, Bellinghausen LK, Song AS, Petrova YM, Tuvim MJ, Adachi R, Romo I, Bordt AS, Bowden MG, Sisson JH, Woodruff PG, Thornton DJ, Rousseau K, De la Garza MM, Moghaddam SJ, Karmouty-Quintana H, Blackburn MR, Drouin SM, Davis CW, Terrell KA, Grubb BR, O’Neal WK, Flores SC, Cota-Gomez A, Lozupone CA, Donnelly JA, Watson AM, Hennessy CE, Keith RC, Yang IV, Barthel L, Henson PM, Janssen WJ, Schwartz DA, Boucher RC, Dickey BF, Evans CM. Muc5b is required for airway defense. Nature. 2013;505:412-416. doi: 10.1038/nature12807. PMID: 24317696; PMCID: PMC4001806.
- Ehre C, Worthington EN, Liesman RM, Grubb BR, Barbier D, O’Neal WK, Sallenave JM, Pickles RJ, Boucher RC. Overexpressing mouse model demonstrates the protective role of Muc5ac in the lungs. Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):16528-33. doi: 10.1073/pnas.1206552109. Erratum in: Proc Natl Acad Sci U S A. 2014 Apr 15;111(15):5753. PMID: 23012413; PMCID: PMC3478656.
- Livraghi-Butrico A, Grubb BR, Kelly EJ, Wilkinson KJ, Yang H, Geiser M, Randell SH, Boucher RC, O’Neal WK. Genetically determined heterogeneity of lung disease in a mouse model of airway mucus obstruction. Physiol Genomics. 2012 Apr 15;44(8):470-84. doi: 10.1152/physiolgenomics.00185.2011. PMID: 22395316; PMCID: PMC3339860.
- Livraghi-Butrico A, Kelly EJ, Klem ER, Dang H, Wolfgang MC, Boucher RC, Randell SH, O’Neal WK. Mucus clearance, MyD88-dependent and MyD88-independent immunity modulate lung susceptibility to spontaneous bacterial infection and inflammation. Mucosal Immunol. 2012 Jul;5(4):397-408. doi: 10.1038/mi.2012.17. PMID: 22419116; PMCID: PMC3377774.
- Sun L, Rommens JM, Corvol H, Li W, Li X, Chiang TA, Lin F, Dorfman R, Busson PF, Parekh RV, Zelenika D, Blackman SM, Corey M, Doshi VK, Henderson L, Naughton KM, O’Neal WK, Pace RG, Stonebraker JR, Wood SD, Wright FA, Zielenski J, Clement A, Drumm ML, Boelle PY, Cutting GR, Knowles MR, Durie PR, Strug LJ. Multiple apical plasma membrane constituents are associated with susceptibility to meconium ileus in individuals with cystic fibrosis. Nat Genet. 2012 May;44(5):562-9. doi: 10.1038/ng.2221. PMID: 22466613; PMCID: PMC3371103.
- Guo X, Pace RG, Stonebraker JR, Commander CW, Dang AT, Drumm ML, Harris A, Zou F, Swallow DM, Wright FA, O’Neal WK, Knowles MR. Mucin variable number tandem repeat polymorphisms and severity of cystic fibrosis lung disease: significant association with MUC5AC. PLoS One. 2011;6(10):e25452. doi: 10.1371/journal.pone.0025452. PMID: 21998660; PMCID: PMC3188583.
- Wright FA, Strug LJ, Doshi VK, Commander CW, Blackman SM, Sun L, Berthiaume Y, Cutler D, Cojocaru A, Collaco JM, Corey M, Dorfman R, Goddard K, Green D, Kent JW, Jr., Lange EM, Lee S, Li W, Luo J, Mayhew GM, Naughton KM, Pace RG, Pare P, Rommens J, Sandford A, Stonebraker JR, Sun W, Taylor C, Vanscoy LL, Zou F, Blangero J, Zielenski J, O’Neal WK, Drumm ML, Durie PR, Knowles MR, Cutting GR. Genome-wide association and linkage identify modifier loci of lung disease severity in cystic fibrosis at 11p13 and 20q13.2. Nat Genet. 2011 Jun;43(6):539-46. doi: 10.1038/ng.838. PMID: 21602797; PMCID: PMC3296486.
- Mall MA, Button B, Johannesson B, Zhou Z, Livraghi A, Caldwell RA, Schubert SC, Schultz C, O’Neal WK, Pradervand S, Hummler E, Rossier BC, Grubb BR, Boucher RC. Airway surface liquid volume regulation determines different airway phenotypes in liddle compared with betaENaC-overexpressing mice. J Biol Chem. 2010 Aug 27;285(35):26945-26955. doi: 10.1074/jbc.M110.151803. PMID: 20566636; PMCID: PMC2930694.
- Martino MEB, Jones L, Brighton B, O’Neal WK, Ribeiro CMP. The ER stress transducer IRE1B is a key regulator of airway mucin production. Pediatr Pulmonol. 2010;Suppl. 33 256.
- Livraghi A, Grubb BR, Hudson EJ, Wilkinson KJ, Sheehan JK, Mall MA, O’Neal WK, Boucher RC, Randell SH. Airway and lung pathology due to mucosal surface dehydration in {beta}-epithelial Na+ channel-overexpressing mice: role of TNF-{alpha} and IL-4R{alpha} signaling, influence of neonatal development, and limited efficacy of glucocorticoid treatment. J Immunol. 2009 Apr 1;182(7):4357-67. doi: 10.4049/jimmunol.0802557. PMID: 19299736; PMCID: PMC2659461.
- Mall MA, Harkema JR, Trojanek JB, Treis D, Livraghi A, Schubert S, Zhou Z, Kreda SM, Tilley SL, Hudson EJ, O’Neal WK, Boucher RC. Development of chronic bronchitis and emphysema in beta-epithelial Na+ channel-overexpressing mice. Am J Respir Crit Care Med. 2008 Apr 1;177(7):730-42. doi: 10.1164/rccm.200708-1233OC. PMID: 18079494; PMCID: PMC2277210.
- Rowe SM, Jackson PL, Liu G, Hardison M, Livraghi A, Solomon GM, McQuaid DB, Noerager BD, Gaggar A, Clancy JP, O’Neal W, Sorscher EJ, Abraham E, Blalock JE. Potential role of high-mobility group box 1 in cystic fibrosis airway disease. Am J Respir Crit Care Med. 2008 Oct 15;178(8):822-31. doi: 10.1164/rccm.200712-1894OC. PMID: 18658107; PMCID: PMC2566793.
- Stonebraker JR, Wagner D, Lefensty RW, Burns K, Gendler SJ, Bergelson JM, Boucher RC, O’Neal WK, Pickles RJ. Glycocalyx restricts adenoviral vector access to apical receptors expressed on respiratory epithelium in vitro and in vivo: Role for tethered mucins as barriers to lumenal infection. J Virol. 2004 Dec;78(24):13755-68. doi: 10.1128/JVI.78.24.13755-13768.2004. PMID: 15564484; PMCID: PMC533903.
- O’Neal WK, Rose E, Zhou H, Langston C, Rice K, Carey D, Beaudet AL. Multiple advantages of alpha-fetoprotein as a marker for in vivo gene transfer. Mol Ther. 2000 Dec;2(6):640-8. doi: 10.1006/mthe.2000.0198. PMID: 11124066.
- O’Neal WK, Zhou H, Morral N, Langston C, Parks RJ, Graham FL, Kochanek S, Beaudet AL. Toxicity associated with repeated administration of first-generation adenovirus vectors does not occur with a helper-dependent vector. Mol Med. 2000 Mar;6(3):179-95. PMID: 10965494; PMCID: PMC1949942.
- Morral N, O’Neal W, Rice K, Leland M, Kaplan J, Piedra PA, Zhou H, Parks RJ, Velji R, Aguilar-Cordova E, Wadsworth S, Graham FL, Kochanek S, Carey KD, Beaudet AL. Administration of helper-dependent adenoviral vectors and sequential delivery of different vector serotype for long-term liver-directed gene transfer in baboons. Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12816-21. doi: 10.1073/pnas.96.22.12816. PMID: 10536005; PMCID: PMC23112.
- O’Neal WK, Zhou H, Morral N, Aguilar-Cordova E, Pestaner J, Langston C, Mull B, Wang Y, Beaudet AL, Lee B. Toxicological comparison of E2a-deleted and first-generation adenoviral vectors expressing alpha1-antitrypsin after systemic delivery. Hum Gene Ther. 1998 Jul 20;9(11):1587-98. doi: 10.1089/hum.1998.9.11-1587. PMID: 9694157.
- Morral N, O’Neal W, Zhou H, Langston C, Beaudet A. Immune responses to reporter proteins and high viral dose limit duration of expression with adenoviral vectors: comparison of E2a wild type and E2a deleted vectors. Hum Gene Ther. 1997 Jul 1;8(10):1275-86. doi: 10.1089/hum.1997.8.10-1275. PMID: 9215744.
- Zhou H, O’Neal W, Morral N, Beaudet AL. Development of a complementing cell line and a system for construction of adenovirus vectors with E1 and E2a deleted. J Virol. 1996 Oct;70(10):7030-8. doi: 10.1128/JVI.70.10.7030-7038.1996. PMID: 8794347; PMCID: PMC190753.
- Hasty P, O’Neal WK, Liu KQ, Morris AP, Bebok Z, Shumyatsky GB, Jilling T, Sorscher EJ, Bradley A, Beaudet AL. Severe phenotype in mice with termination mutation in exon 2 of cystic fibrosis gene. Somat Cell Mol Genet. 1995 May;21(3):177-87. doi: 10.1007/BF02254769. PMID: 7482032.
- O’Neal WK, Hasty P, McCray PB, Jr., Casey B, Rivera-Perez J, Welsh MJ, Beaudet AL, Bradley A. A severe phenotype in mice with a duplication of exon 3 in the cystic fibrosis locus. Hum Mol Genet. 1993 Oct;2(10):1561-9. doi: 10.1093/hmg/2.10.1561. PMID: 7505691.
- Yorifuji T, Lemna WK, Ballard CF, Rosenbloom CL, Rozmahel R, Plavsic N, Tsui LC, Beaudet AL. Molecular cloning and sequence analysis of the murine cDNA for the cystic fibrosis transmembrane conductance regulator. Genomics. 1991 Jul;10(3):547-50. doi: 10.1016/0888-7543(91)90434-g. PMID: 1716243.
- Lemna WK, Feldman GL, Kerem BT, Fernbach SD, Zevkovich EP, O’Brien WE, Riordan JR, Collins FS, Tsui LC, Beaudet AL. Mutation analysis for heterozygote detection and the prenatal diagnosis of cystic fibrosis. N Engl J Med. 1990 Feb 1;322(5):291-6. doi: 10.1056/NEJM199002013220503. PMID: 2296270.