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James S. Hagood, MD

Professor

Professor of Pediatrics, Division of Pulmonology, UNC School of Medicine
Director, Program for Rare and Interstitial Lung Disease, Children’s Research Institute and Marsico Lung Institute

Research Focus:

In the laboratory, we study the regulation of fibroblast phenotype in the context of pulmonary fibrosis and lung development. The current principal interests of my lab are: regulation of expression of Thy-1, a fibrosis suppressor, by transcriptional silencing and vesicular shedding; roles and regulation of fibroblast differentiation in lung alveolar development; epigenomic alterations in lung development and fibrogenesis; targeted delivery of antifibrotic therapies to the fibrotic lung; the roles of extracellular vesicles in lung fibrosis progression and resolution; and mechanisms of Thy-1 signaling regulating myofibroblastic adhesion, migration, differentiation and survival.

External Links:

LungMAP

The Human BioMolecular Atlas Program (HubMAP)

UNC Children’s Research Institute

Selected Recent Publications:

  1. Jain S, Pei L, Spraggins JM, Angelo M, Carson JP, Gehlenborg N, Ginty F, Gonçalves JP, Hagood JS, Hickey JW, Kelleher NL, Laurent LC, Lin S, Lin Y, Liu H, Naba A, Nakayasu ES, Qian WJ, Radtke A, Robson P, Stockwell BR, Van de Plas R, Vlachos IS, Zhou M; HuBMAP Consortium; Börner K, Snyder MP. Advances and prospects for the Human BioMolecular Atlas Program (HuBMAP). Nat Cell Biol. 2023 Aug;25(8):1089-1100. doi: 10.1038/s41556-023-01194-w. PMID: 37468756. PMCID: PMC10681365.
  2. McKinzie CJ, Gower WA, Hagood JS, Vece TJ. Use of pirfenidone in pediatric patients with interstitial lung disease and pulmonary fibrosis. Pediatr Pulmonol. 2023 Aug;58(8):2396-2398. doi: 10.1002/ppul.26465. PMID: 37161910.
  3. Nevel RJ, Deutsch GH, Craven D, Deterding R, Fishman MP, Wambach JA, Casey A, Krone K, Liptzin DR, O’Connor MG, Kurland G, Taylor JB, Gower WA, Hagood JS, Conrad C, Tam-Williams JB, Fiorino EK, Goldfarb S, Sadreameli SC, Nogee LM, Montgomery G, Hamvas A, Laguna TA, Bansal M, Lew C, Santiago M, Popova A, De A, Chan M, Powers MR, Josephson MB, Camburn D, Voss L, Li Y, Young LR; chILD Registry Collaborative. The US national registry for childhood interstitial and diffuse lung disease: Report of study design and initial enrollment cohort. Pediatr Pulmonol. 2023 Jul 4. doi: 10.1002/ppul.26568. Epub ahead of print. PMID: 37401889.
  4. Li R, Sone N, Gotoh S, Sun X, Hagood JS. Contemporary and emerging technologies for research in children’s rare and interstitial lung disease. Pediatr Pulmonol. 2023 May 19. doi: 10.1002/ppul.26490. Epub ahead of print. PMID: 37204232.
  5. Gutierrez MJ, Nino G, Sun D, Restrepo-Gualteros S, Sadreameli SC, Fiorino EK, Wu E, Vece T, Hagood JS, Maglione PJ, Kurland G, Koumbourlis A, Sullivan KE. The lung in inborn errors of immunity: From clinical disease patterns to molecular pathogenesis. J Allergy Clin Immunol. 2022 Dec;150(6):1314-1324. doi: 10.1016/j.jaci.2022.08.024. PMID: 36244852. PMCID: PMC9826631.
  6. Vece TJ, Gower WA, Davis SD, Austin A, McKinzie CJ, Hatch JE, Davis M, Hagood JS. Building a pediatric rare lung disease program: It takes a community of villages. Pediatr Pulmonol. 2022 Nov;57(11):2583-2588. doi: 10.1002/ppul.26083. PMID: 35932221.
  7. 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.
  8. Hu P, Leyton L, Hagood JS, Barker TH. Thy-1-Integrin Interactions in cis and Trans Mediate Distinctive Signaling. Front Cell Dev Biol. 2022 Jun 6;10:928510. doi: 10.3389/fcell.2022.928510. PMID: 35733855; PMCID: PMC9208718.
  9. McKinzie CJ, Hagood JS, Fiorino EK, Fishman MP, Nevel RJ, Gower WA, Vece TJ. The role of pharmacy services beyond cystic fibrosis: A case for support in childhood interstitial lung disease. Pediatr Pulmonol. 2022 Jun;57(6):1535-1536. doi: 10.1002/ppul.25883. PMID: 35246971.
  10. Jackson WM, Santos HP Jr, Hartwell HJ, Gower WA, Chhabra D, Hagood JS, Laughon MM, Payton A, Smeester L, Roell K, O’Shea TM, Fry RC. Differential placental CpG methylation is associated with chronic lung disease of prematurity. Pediatr Res. 2022 May;91(6):1428-1435. doi: 10.1038/s41390-021-01868-x. PMID: 34857876. PMCID: PMC9160210.
  11. Duong TE, Wu Y, Sos BC, Dong W, Limaye S, Rivier LH, Myers G, Hagood JS, Zhang K. A single-cell regulatory map of postnatal lung alveologenesis in humans and mice. Cell Genom. 2022 Mar 9;2(3):100108. doi: 10.1016/j.xgen.2022.100108. PMID: 35434692; PMCID: PMC9012447.
  12. Bradford L, Ross MK, Minso J, Cernelc-Kohan M, Shayan K, Wong SS, Li X, Rivier L, Jegga AG, Deutsch GH, Vece TJ, Loughlin CE, Gower WA, Hurley C, Furman W, Stokes D, Hagood JS. Interstitial lung disease in children with Rubinstein-Taybi syndrome. Pediatr Pulmonol. 2022 Jan;57(1):264-272. doi: 10.1002/ppul.25709. PMID: 34585851.
  13. Martin M, Zhang J, Miao Y, He M, Kang J, Huang HY, Chou CH, Huang TS, Hong HC, Su SH, Wong SS, Harper RL, Wang L, Bhattacharjee R, Huang HD, Chen ZB, Malhotra A, Rabinovitch M, Hagood JS, Shyy JY. Role of endothelial cells in pulmonary fibrosis via SREBP2 activation. JCI Insight. 2021 Nov 22;6(22):e125635. doi: 10.1172/jci.insight.125635. PMID: 34806652. PMCID: PMC8663776.
  14. Li X, Wong SS, Tan C, Espinoza CR, Hagood JS. Loss of Thy-1 may reduce lung regeneration after pneumonectomy in mice. Minerva Med. 2021 Oct;112(5):622-630. doi: 10.23736/S0026-4806.20.06691-4. PMID: 32696636.
  15. Nishio T, Koyama Y, Liu X, Rosenthal SB, Yamamoto G, Fuji H, Baglieri J, Li N, Brenner LN, Iwaisako K, Taura K, Hagood JS, LaRusso NF, Bera TK, Pastan I, Brenner DA, Kisseleva T. Immunotherapy-based targeting of MSLN+ activated portal fibroblasts is a strategy for treatment of cholestatic liver fibrosis. Proc Natl Acad Sci U S A. 2021 Jul 20;118(29):e2101270118. doi: 10.1073/pnas.2101270118. PMID: 34253615. PMCID: PMC8307749.
  16. Tamburro RF, Cooke KR, Davies SM, Goldfarb S, Hagood JS, Srinivasan A, Steiner ME, Stokes D, DiFronzo N, El-Kassar N, Shelburne N, Natarajan A; Pulmonary Complications of Pediatric Hematopoietic Stem Cell Transplantation Workshop Participants. Pulmonary Complications of Pediatric Hematopoietic Stem Cell Transplantation (HCT): An NIH Workshop Summary. Ann Am Thorac Soc. 2021 Mar;18(3):381-394. doi: 10.1513/AnnalsATS.202001-006OT. PMID: 33058742. PMCID: PMC7919149.
  17. Maldonado H, Hagood JS. Cooperative signaling between integrins and growth factor receptors in fibrosis. J Mol Med (Berl). 2021 Feb;99(2):213-224. doi: 10.1007/s00109-020-02026-2. PMID: 33392631.
  18. Vece TJ, Wambach JA, Hagood JS. Childhood rare lung disease in the 21st century: “-omics” technology advances accelerating discovery. Pediatr Pulmonol. 2020 Jul;55(7):1828-1837. doi: 10.1002/ppul.24809. PMID: 32533908.
  19. Gower WA, Hagood JS. To Bx, or not to Bx, that is the question. Pediatr Pulmonol. 2020 Jun;55(6):1303-1304. doi: 10.1002/ppul.24797. PMID: 32364314.
  20. Liptzin DR, Pickett K, Brinton JT, Agarwal A, Fishman MP, Casey A, Towe CT, Taylor JB, Kurland G, Hagood JS, Wambach J, Srivastava R, Al-Saleh H, Dell SD, Young LR, Deterding RR. Neuroendocrine Cell Hyperplasia of Infancy: Clinical Score and Comorbidities. Ann Am Thorac Soc. 2020 Jun;17(6):724-72. doi: 10.1513/AnnalsATS.201908-617OC. PMID: 32109152. PMCID: PMC7258416.
  21. Worthington EN, Hagood JS. Therapeutic Use of Extracellular Vesicles for Acute and Chronic Lung Disease. Int J Mol Sci. 2020 Mar 27;21(7). doi: 10.3390/ijms21072318. PMID: 32230828. PMCID: PMC7177288.
  22. Zemans RL, Hagood JS. Diversity at the border. Nat Immunol. 2020 Feb;21(2):112-114. doi: 10.1038/s41590-019-0585-9. PMID: 31959978.
  23. Ding J, Ahangari F, Espinoza CR, Chhabra D, Nicola T, Yan X, Lal CV, Hagood JS, Kaminski N, Bar-Joseph Z, Ambalavanan N. Integrating multi-omics longitudinal data to reconstruct networks underlying lung development. Am J Physiol Lung Cell Mol Physiol. 2019 Nov 1;317(5):L556-L568. doi: 10.1152/ajplung.00554.2018. PMID: 31432713; PMCID: PMC6879899.
  24. Tan C, Jiang M, Wong SS, Espinoza CR, Kim C, Li X, Connors E, Hagood JS. Soluble Thy-1 reverses lung fibrosis via its integrin-binding motif. JCI Insight. 2019 Nov 1;4(21). doi: 10.1172/jci.insight.131152. PMID: 31672942. PMCID: PMC6948761.
  25. Negreros M, Hagood JS, Espinoza CR, Balderas-Martínez YI, Selman M, Pardo A. Transforming growth factor beta 1 induces methylation changes in lung fibroblasts. PLoS One. 2019 Oct 11;14(10):e0223512. doi: 10.1371/journal.pone.0223512. PMID: 31603936; PMCID: PMC6788707.
  26. Hagood JS. Thy-1 as an Integrator of Diverse Extracellular Signals. Front Cell Dev Biol. 2019 Feb 25;7:26. doi: 10.3389/fcell.2019.00026. PMID: 30859102; PMCID: PMC6397883.
  27. Shentu TP, Hagood JS. Outsourcing Invasion, a Novel Function for Extracellular Vesicles in the Lung. Am J Respir Cell Mol Biol. 2019 Mar;60(3):251-252. doi: 10.1165/rcmb.2018-0345ED. PMID: 30372117.
  28. Fiore VF, Wong SS, Tran C, Tan C, Xu W, Sulchek T, White ES, Hagood JS, Barker TH. αvβ3 Integrin drives fibroblast contraction and strain stiffening of soft provisional matrix during progressive fibrosis. JCI Insight. 2018 Oct 18;3(20). doi: 10.1172/jci.insight.97597. PMID: 30333317; PMCID: PMC6237458.
  29. Duong TE, Hagood JS. Epigenetic Regulation of Myofibroblast Phenotypes in Fibrosis. Curr Pathobiol Rep. 2018 Mar;6(1):79-96. doi: 10.1007/s40139-018-0155-0. PMID: 30271681; PMCID: PMC6159951.
  30. Ding J, Hagood JS, Ambalavanan N, Kaminski N, Bar-Joseph Z. iDREM: Interactive visualization of dynamic regulatory networks. PLoS Comput Biol. 2018 Mar 14;14(3):e1006019. doi: 10.1371/journal.pcbi.1006019. PMID: 29538379; PMCID: PMC5868853.
  31. Shentu TP, Huang TS, Cernelc-Kohan M, Chan J, Wong SS, Espinoza CR, Tan C, Gramaglia I, van der Heyde H, Chien S, Hagood JS. Thy-1 dependent uptake of mesenchymal stem cell-derived extracellular vesicles blocks myofibroblastic differentiation. Sci Rep. 2017 Dec 22;7(1):18052. doi: 10.1038/s41598-017-18288-9. PMID: 29273797; PMCID: PMC5741716.
  32. Joshi S, Singh AR, Wong SS, Zulcic M, Jiang M, Pardo A, Selman M, Hagood JS, Durden DL. Rac2 is required for alternative macrophage activation and bleomycin induced pulmonary fibrosis; a macrophage autonomous phenotype. PLoS One. 2017 Aug 17;12(8):e0182851. doi: 10.1371/journal.pone.0182851. PMID: 28817691; PMCID: PMC5560537.
  33. Liu X, Wong SS, Taype CA, Kim J, Shentu TP, Espinoza CR, Finley JC, Bradley JE, Head BP, Patel HH, Mah EJ, Hagood JS. Thy-1 interaction with Fas in lipid rafts regulates fibroblast apoptosis and lung injury resolution. Lab Invest. 2017 Mar;97(3):256-267. doi: 10.1038/labinvest.2016.145. PMID: 28165468; PMCID: PMC5663248.
  34. Kleyman M, Sefer E, Nicola T, Espinoza C, Chhabra D, Hagood JS, Kaminski N, Ambalavanan N, Bar-Joseph Z. Selecting the most appropriate time points to profile in high-throughput studies. Elife. 2017 Jan 26;6. doi: 10.7554/eLife.18541. PMID: 28124972; PMCID: PMC5319842.
  35. Glasser SW, Hagood JS, Wong S, Taype CA, Madala SK, Hardie WD. Mechanisms of Lung Fibrosis Resolution. Am J Pathol. 2016 May;186(5):1066-77. doi: 10.1016/j.ajpath.2016.01.018. Review. PMID: 27021937; PMCID: PMC4861766.
  36. Checa M, Hagood JS, Velazquez-Cruz R, Ruiz V, García-De-Alba C, Rangel-Escareño C, Urrea F, Becerril C, Montaño M, García-Trejo S, Cisneros Lira  J, Aquino-Gálvez A, Pardo A, Selman M. Cigarette Smoke Enhances the Expression of Profibrotic Molecules in Alveolar Epithelial Cells. PLoS One. 2016 Mar 2;11(3):e0150383. doi: 10.1371/journal.pone.0150383. PMID: 26934369; PMCID: PMC4775036.
  37. Fiore VF, Strane PW, Bryksin AV, White ES, Hagood JS, Barker TH. Conformational coupling of integrin and Thy-1 regulates Fyn priming and fibroblast mechanotransduction. J Cell Biol. 2015 Oct 12;211(1):173-90. doi: 10.1083/jcb.201505007. PMID: 26459603; PMCID: PMC4602038.
  38. Fan LL, Dishop MK, Galambos C, Askin FB, White FV, Langston C, Liptzin DR, Kroehl ME, Deutsch GH, Young LR, Kurland G, Hagood J, Dell S, Trapnell BC, Deterding RR; Children’s Interstitial and Diffuse Lung Disease Research Network (chILDRN). Diffuse Lung Disease in Biopsied Children 2 to 18 Years of Age. Application of the chILD Classification Scheme. Ann Am Thorac Soc. 2015 Oct;12(10):1498-505. doi: 10.1513/AnnalsATS.201501-064OC. PMID: 26291470; PMCID: PMC4627419.
  39. Leyton L, Hagood JS. Thy-1 modulates neurological cell-cell and cell-matrix interactions through multiple molecular interactions. Adv Neurobiol. 2014;8:3-20. Review. PMID: 25300130.
  40. Sanders YY, Hagood JS, Liu H, Zhang W, Ambalavanan N, Thannickal VJ. Histone deacetylase inhibition promotes fibroblast apoptosis and ameliorates pulmonary fibrosis in mice. Eur Respir J. 2014 May;43(5):1448-58. doi: 10.1183/09031936.00095113. PMID: 24603818.
  41. Harris WT, Kelly DR, Zhou Y, Wang D, MacEwen M, Hagood JS, Clancy JP, Ambalavanan N, Sorscher EJ. Myofibroblast differentiation and enhanced TGF-B signaling in cystic fibrosis lung disease. PLoS One. 2013 Aug 12;8(8):e70196. doi: 10.1371/journal.pone.0070196. Erratum in: PLoS One. 2013;8(8). doi:10.1371/annotation/d0132de3-56ca-4258-9119-bdab0ceb2cff. Macewen, Mark [corrected to MacEwen, Mark]. PMID: 23950911; PMCID: PMC3741283.
  42. Kurland G, Deterding RR, Hagood JS, Young LR, Brody AS, Castile RG, Dell S, Fan LL, Hamvas A, Hilman BC, Langston C, Nogee LM, Redding GJ; American Thoracic Society Committee on Childhood Interstitial Lung Disease (chILD) and the chILD Research Network. An official American Thoracic Society clinical practice guideline: classification, evaluation, and management of childhood interstitial lung disease in infancy. Am J Respir Crit Care Med. 2013 Aug 1;188(3):376-94. doi: 10.1164/rccm.201305-0923ST. Review. PMID: 23905526; PMCID: PMC3778735.
  43. Hamvas A, Deterding R, Balch WE, Schwartz DA, Albertine KH, Whitsett JA, Cardoso WV, Kotton DN, Kourembanas S, Hagood JS. Diffuse lung disease in children: summary of a scientific conference. Pediatr Pulmonol. 2014 Apr;49(4):400-9. doi: 10.1002/ppul.22805. PMID: 23798474; PMCID: PMC4145861.
  44. Bradley JE, Chan JM, Hagood JS. Effect of the GPI anchor of human Thy-1 on antibody recognition and function. Lab Invest. 2013 Mar;93(3):365-74. doi: 10.1038/labinvest.2012.178. PMID: 23358110; PMCID: PMC5662197.

For further publications, please see PubMed.