Publications

Genetics and Genomics of Pulmonary Fibrosis

Peljto AL, Blumhagen RZ, Walts AD, Cardwell J, Powers J, Corte TJ, Dickinson JL, Glaspole I, Moodley YP, Vasakova MK, Bendstrup E, Davidsen JR, Borie R, Crestani B, Dieude P, Bonella F, Costabel U, Gudmundsson G, Donnelly SC, Egan J, Henry MT, Keane MP, Kennedy MP, McCarthy C, McElroy AN, Olaniyi JA, O'Reilly KMA, Richeldi L, Leone PM, Poletti V, Puppo F, Tomassetti S, Luzzi V, Kokturk N, Mogulkoc N, Fiddler CA, Hirani N, Jenkins G, Maher TM, Molyneaux PL, Parfrey H, Braybrooke R, Blackwell TS, Jackson PD, Nathan SD, Porteous MK, Brown KK, Christie JD, Collard HR, Eickelberg O, Foster EE, Gibson KF, Glassberg M, Kass D, Kropski JA, Lederer D, Linderholm AL, Loyd J, Mathai SK, Montesi SB, Noth I, Oldham JM, Palmisciano AJ, Reichner CA, Rojas M, Roman J, Schluger N, Shea BS, Swigris JJ, Wolters PJ, Zhang Y, Prele CMA, Enghelmayer JI, Otaola M, Ryerson CJ, Salinas M, Sterclova M, Gebremariam TH, Myllärniemi M, Carbone R, Furusawa H, Hirose M, Inoue Y, Miyazaki Y, Ohta K, Ohta S, Okamoto T, Kim DS, Pardo A, Selman M, Aranda AU, Park MS, Park JS, Song JW, Molina-Molina M, Planas-Cerezales L, Westergren-Thorsson G, Smith AV, Manichaikul AW, Kim JS, Rich SS, Oelsner EC, Barr RG, Rotter JI, Dupuis J, O'Connor G, Vasan RS, Cho MH, Silverman EK, Schwarz MI, Steele MP, Lee JS, Yang IV, Fingerlin TE, Schwartz DA; NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium.

Idiopathic Pulmonary Fibrosis Is Associated with Common Genetic Variants and Limited Rare Variants. Am J Respir Crit Care Med. 2023 Online ahead of print. [PMID: 36602845] 

Steele MP, Peljto AL, Mathai SK, Humphries S, Bang TJ, Oh A, Teague S, Cicchetti G, Sigakis C, Kropski JA, Loyd JE, Blackwell TS, Brown KK, Schwarz MI, Warren RA, Powers J, Walts AD, Markin C, Fingerlin TE, Yang IV, Lynch DA, Lee JS, Schwartz DA. Incidence and Progression of Fibrotic Lung Disease in an At-Risk Cohort. Am J Respir Crit Care Med. 2022 [PMID: 36094461]

Borie R, Cardwell J, Konigsberg IR, Moore CM, Zhang W, Sasse SK, Gally F, Dobrinskikh E, Walts A, Powers J, Brancato J, Rojas M, Wolters PJ, Brown KK, Blackwell T, Nakanishi T, Richards JB, Gerber AN, Fingerlin TE, Sachs N, Pulit SL, Zappala Z, Schwartz DA, Yang IV.  Colocalization of gene expression and DNA methylation with genetic risk variants supports functional roles of MUC5B and DSP in idiopathic pulmonary fibrosis.  Am J Respir Crit Care Med 2022;206:1259-1270. [PMID: 35816432]   Drs. Schwartz and Yang are joint last authors.

Moore C, Blumhagen RZ, Yang IV, Walts A, Powers J, Walker T, Bishop M, Russell P, Vestal B, Cardwell J, Markin CR, Mathai SK, Schwarz MI, Steele MP, Lee J, Brown KK, Loyd JE, Crapo JD, Silverman EK, Cho MH, James JA, Guthridge JM, Cogan JD, Kropski JA, Swigris JJ, Bair C, Kim DS, Ji W, Kim H, Song JW, Maier LA, Pacheco KA, Hirani N, Poon AS, Li F, Jenkins RG, Braybrooke R, Saini G, Maher TM, Molyneaux PL, Saunders P, Zhang Y, Gibson KF, Kass DJ, Rojas M, Sembrat J, Wolters PJ, Collard HR, Sundy JS, O'Riordan T, Strek ME, Noth I, Ma SF, Porteous MK, Kreider ME, Patel NB, Inoue Y, Hirose M, Arai T, Akagawa S, Eickelberg O, Fernandez IE, Behr J, Mogulkoc N, Corte TJ, Glaspole I, Tomassetti S, Ravaglia C, Poletti V, Crestani B, Borie R, Kannengiesser C, Parfrey H, Fiddler C, Rassl D, Molina-Molina M, Machahua C, Worboys AM, Gudmundsson G, Isaksson HJ, Lederer DJ, Podolanczuk AJ, Montesi SB, Bendstrup E, Danchel V, Selman M, Pardo A, Henry MT, Keane MP, Doran P, Vašáková M, Sterclova M, Ryerson CJ, Wilcox PG, Okamoto T, Furusawa H, Miyazaki Y, Laurent G, Baltic S, Prele C, Moodley Y, Shea BS, Ohta K, Suzukawa M, Narumoto O, Nathan SD, Venuto DC, Woldehanna ML, Kokturk N, de Andrade JA, Luckhardt T, Kulkarni T, Bonella F, Donnelly SC, McElroy A, Armstong ME, Aranda A, Carbone RG, Puppo F, Beckman KB, Nickerson DA, Fingerlin TE, Schwartz DA. Resequencing Study Confirms That Host Defense and Cell Senescence Gene Variants Contribute to the Risk of Idiopathic Pulmonary Fibrosis. Am J Resp Crit Care Med 2019; 200:199-208. [PMID: 31034279] 

Juge PA, Lee JS, Ebstein E, Furukawa H, Dobrinskikh E, Gazal S, Kannengiesser C, Ottaviani S, Oka S, Tohma S, Tsuchiya N, Rojas-Serrano J, González-Pérez MI, Mejía M, Buendía-Roldán I, Falfán-Valencia R, Ambrocio-Ortiz E, Manali E, Papiris SA, Karageorgas T, Boumpas D, Antoniou K, van Moorsel CHM, van der Vis J, de Man YA, Grutters JC, Wang Y, Borie R, Wemeau-Stervinou L, Wallaert B, Flipo RM, Nunes H, Valeyre D, Saidenberg-Kermanac'h N, Boissier MC, Marchand-Adam S, Frazier A, Richette P, Allanore Y, Sibilia J, Dromer C, Richez C, Schaeverbeke T, Lioté H, Thabut G, Nathan N, Amselem S, Soubrier M, Cottin V, Clément A, Deane K, Walts AD, Fingerlin T, Fischer A, Ryu JH, Matteson EL, Niewold TB, Assayag D, Gross A, Wolters P, Schwarz MI, Holers M, Solomon JJ, Doyle T, Rosas IO, Blauwendraat C, Nalls MA, Debray MP, Boileau C, Crestani B, Schwartz DA, Dieudé P. MUC5B Promoter Variant and Rheumatoid Arthritis with Interstitial Lung Disease. N Engl J Med 2018; 379:2209-2219. [PMID: 30345907].   Drs. Schwartz and Dieudé are joint last authors. 

Yang IV, Pedersen BS, Rabinovich E, Hennessy CE, Davidson EJ, Murphy E, Juan Guardela B, Tedrow JR, Zhang Y, Singh MK, Correll M, Schwarz MI, Geraci M, Sciurba FC, Quackenbush J, Spira A, Kaminski N, Schwartz DA. Relationship of DNA Methylation and Gene Expression in Idiopathic Pulmonary Fibrosis (IPF). Am J Respir Crit Care Med 2014; 190:1263-1272. [PMID: 25333685] 

Fingerlin TE, Murphy E, Zhang W, Peljto AL, Brown KK, Steele MP, Loyd JE, Cosgrove GP, Lynch D, Groshong S, Collard HR, Wolters PJ, Bradford WZ, Kossen K, Seiwert SD, du Bois RM, Garcia CK, Devine MS, Gudmundsson G, Isaksson HJ, Kaminski N, Zhang Y, Gibson KF, Lancaster LH, Cogan JD, Mason WR, Maher TM, Molyneaux PL, Wells AU, Moffatt MF, Selman M, Pardo A, Kim DS, Crapo JD, Make BJ, Regan EA, Walek DS, Daniel JJ, Kamatani Y, Zelenika D, Smith K, McKean D, Pedersen BS, Talbert J, Kidd RN, Markin CR, Beckman KB, Lathrop M, Schwarz MI, Schwartz DA. Genome-wide association study identifies multiple susceptibility loci for pulmonary fibrosis. Nat Genet 2013; 45:613-620. [PMID: 23583980]

Hunninghake GM, Hatabu H, Okajima Y, Gao W, Dupuis J, Latourelle JC, Nishino M, Araki T, Zazueta OE, Kurugol S, Ross JC, San Jose Estepar R, Murphy E, Steele MP, Loyd JE, Schwarz MI, Fingerlin TE, Rosas IO, Washko GR, O'Connor GT, Schwartz DA. Muc5b promoter polymorphism and interstitial lung abnormalities. N Engl J Med 2013; 368:2192-200. [PMID: 23692170] 

Peljto AL, Zhang Y, Fingerlin TE, Ma SF, Garcia JG, Richards TJ, Silveira LJ, Lindell KO, Steele MP, Loyd JE, Gibson KF, Seibold MA, Brown KK, Talbert JL, Markin C, Kossen K, Seiwert SD, Murphy E, Noth I, Schwarz MI, Kaminski N, Schwartz DA. Association between the muc5b promoter polymorphism and survival in patients with idiopathic pulmonary fibrosis. JAMA 2013; 309:2232-9. [PMID: 23695349]

Yang IV, Coldren CD, Leach SM, Seibold MA, Murphy E, Lin J, Rosen R, Neidermyer AJ, McKean DF, Groshong SD, Cool C, Cosgrove GP, Lynch DA, Brown KK, Schwarz MI, Fingerlin TE, Schwartz DA. Expression of cilium-associated genes defines novel molecular subtypes of idiopathic pulmonary fibrosis. Thorax 2013; 68:1114-21. [PMID: 23783374]

Seibold MA, Wise AL, Speer MC, Steele MP, Brown KK, Loyd JE, Fingerlin TE, Zhang W, Gudmundsson G, Groshong SD, Evans CM, Garantziotis S, Adler KB, Dickey BF, du Bois RM, Yang IV, Herron A, Kervitsky D, Talbert JL, Markin C, Park J, Crews AL, Slifer SH, Auerbach S, Roy MG, Lin J, Hennessy CE, Schwarz MI, and Schwartz DA.A common polymorphism in the putative promoter of MUC5B is associated with familial interstitial pneumonia (FIP) and idiopathic pulmonary fibrosis (IPF). N Engl J Med 2011; 364:1503-1512. [PMID: 21506741]

Transcriptional Regulation of MUC5B

Gally F, Sasse SK, Kurche JS, Gruca MA, Cardwell JH, Okamoto T, Chu HW, Hou X, Poirion OB, Buchanan J, Preissl S, Ren B, Colgan SP, Dowell RD, Yang IV, Schwartz DA, Gerber AN. The MUC5B-associated variant rs35705950 resides within an enhancer subject to lineage- and disease-dependent epigenetic remodeling.

JCI Insight 2021; 6:144294. [PMID: 33320836]

Helling BA, Gerber AN, Kadiyala V, Sasse SK, Pedersen BS, Sparks L, Nakano Y, Okamoto T, Evans CM, Yang IV, Schwartz DA. Regulation of MUC5B Expression in Idiopathic Pulmonary Fibrosis. Am J Respir Cell Mol Biol 2017; 57:91-99. [PMID: 28272906]

Nakano Y, Yang IV, Walts A, Watson AM, Helling BA, Fletcher AA, Lara AR, Schwarz MI, Evans CM, Schwartz DA. MUC5B Promoter Variant rs35705950 Affects MUC5B Expression in the Distal Airways in Idiopathic Pulmonary Fibrosis. Am J Respir Crit Care Med 2016; 193:464-466.  [PMID: 26871673]

Functional Genomics of MUC5B

Dobrinskikh E, Hennessy CE, Kurche JS, Kim E, Estrella AM, Cardwell J, Yang IV, Schwartz DA.

Epithelial Endoplasmic Reticulum Stress Enhances the Risk of Muc5b-associated Lung Fibrosis.

Am J Respir Cell Mol Biol. 2023; 68:62-74. [ PMID: 36108173]  Drs. Schwartz and Yang are joint last authors.

Stancil IT, Michalski JE, Hennessy CE, Hatakka KL, Yang IV, Kurche JS, Rincon M, Schwartz DA. Interleukin-6-dependent epithelial fluidization initiates fibrotic lung remodeling. Sci Transl Med 2022; 14:eabo5254 [PMID: 35857823]

Stancil IT, Michalski JE, Davis-Hall D, Chu HW, Park JA, Magin CM, Yang IV, Smith BJ, Dobrinskikh E, Schwartz DA. Pulmonary fibrosis distal airway epithelia are dynamically and structurally dysfunctional.
Nature Commun 2021; 12:4566.  [PMID: 34315881]

Hancock LA, Hennessy CE, Solomon GM, Dobrinskikh E, Estrella A, Hara N, Hill DB, Kissner WJ, Markovetz MR, Grove Villalon DE, Voss ME, Tearney GJ, Carroll KS, Shi Y, Schwarz MI, Thelin WR, Rowe SM, Yang IV, Evans CM, Schwartz DA. Muc5b overexpression causes mucociliary dysfunction and enhances lung fibrosis in mice. Nature Commun 2018; 9:5363-5372. [PMID:30560893]

Ciliogenesis in IPF

Kim E, Mathai SK, Stancil IT, Ma X, Hernandez-Gutierrez A, Becerra JN, Marrero-Torres E, Hennessy CE, Hatakka K, Wartchow EP, Estrella A, Huber JP, Cardwell JH, Burnham EL, Zhang Y, Evans CM, Vladar EK, Schwartz DA, Dobrinskikh E, Yang IV. Aberrant Multiciliogenesis in Idiopathic Pulmonary Fibrosis. Am J Respir Cell Mol Biol, 2022 (Online ahead of print) [PMID: 35608953]

Sarcoidosis Epigenetics

Liao SY, Atif SM, Mould K, Konigsberg IR, Fu R, Davidson E, Li L, Fontenot AP, Maier LA, Yang IV. Single-cell RNA sequencing identifies macrophage transcriptional heterogeneities in granulomatous diseases. Eur Respir J. 2021;57:2003794.

Reviews

Sharma S, Yang IV, Schwartz DA.  Epigenetic regulation of immune function in asthma.  J Allergy Clin Immunol 2022 (Online ahead of print) [PMID: 35717251] 

Stancil IT, Michalski JE, Schwartz DA.  An airway-centric view of idiopathic pulmonary fibrosis.  Am J Respir Crit Care Med, 2022 (Online ahead of print) [PMID: 35446237]

Konigsberg IR, Maier LA, Yang IV. Epigenetics and sarcoidosis. Eur Respir Rev. 2021;30:210076.

Yang IV, Lozupone CA, Schwartz DA.  The Environment, the Epignome, and Asthma.  J Allergy Clin Immunol 2017; 140:14-23.  [PMID: 28673400]

Evans CM, Fingerlin TE, Schwarz MI, Lynch D, Kurche J, Warg L, Yang IV, Schwartz DA. Idiopathic Pulmonary Fibrosis: A Genetic Disease That Involves Mucociliary Dysfunction of the Peripheral Airways.

Physiol Rev 2016; 96:1967-1991. [PMID: 27630174]

Davidson EJ, Yang IV. Role of epigenetics in the development of childhood asthma. Curr Opin Allergy Clin Immunol. 2018 Apr;18(2):132-138. doi: 10.1097/ACI.0000000000000429. [PMID: 29389731]

Yang IV, Schwartz DA. Epigenetics of Idiopathic Pulmonary Fibrosis. Transl Res 2015; 165:48-60.  [PMID: 24746870]

Helling BA, Yang IV. Epigenetics in lung fibrosis: from pathobiology to treatment perspective.

Curr Opin Pulm Med. 2015 Sep;21(5):454-62. doi: 10.1097/MCP.0000000000000191. [PMID: 26176965]

Editorials

Schwartz DA, Blumhagen RZ, Fingerlin TE.  Evolution of the gain-of-function MUC5B promoter variant.  Am J Respir Crit Care Med 2022 (Online ahead of print) [PMID: 35830265] 

Burden M, Flores S, Schwartz DA. COVID-19: a time to reinvest in our scientists.  Am J Respir Crit Care Med 2021; 203:1190-1191. [PMID: 33596390]

Konigsberg IR, Yang IV. It's in the (Epi)genetics: Effects of DNA Methylation on Gene Expression in Atopic Asthma? Chest. 2020 Nov;158(5):1799-1801. doi: 10.1016/j.chest.2020.07.050.

Dobrinskikh E, Yang IV. Unraveling the role of MUC5B in idiopathic interstitial pneumonias (IIPs).

Thorax. 2020 Oct;75(10):830. doi: 10.1136/thoraxjnl-2020-215406

Kim E, Yang IV. Selective Regulation of the Airway Mucin MUC5B in the Distal Airway. Am J Respir Crit Care Med. 2019 Jul 15;200(2):129-131

Schwartz DA. Physician-Scientists:  The Bridge Between Medicine and Science. Am J Resp Crit Care Med 2012;185:595-596.  [PMID: 22422900]

Complete lists of Drs. Schwartz and Yang’s publications can be found here:

https://www.ncbi.nlm.nih.gov/myncbi/1ti3sh6SFMrko/bibliography/public/

https://www.ncbi.nlm.nih.gov/sites/myncbi/1felvqhgoep/bibliography/40968394/public/