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Jin-Ah Park, Ph.D.

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Biography
2017
International Research Visiting Fellowship (The University of Newcastle, Australia)
2014
Ann Woolcock Memorial Award (American Thoracic Society)
2013 - 2016
Parker B. Francis Fellowship
2013 - 2016
Scientist Development Grant, AHA

Overview
My research focuses on the role of airway epithelium in the lung. The airway epithelium is the first line of defense against external stimuli. Airway epithelial cells lining on the airway epithelium contribute to homeostasis in the lung, but when they are exposed to excessive biochemical or physical stimuli, the normal defense mechanism turns into the progression of various pathophysiologic conditions. Airway epithelial cells also play important roles in innate and adaptive immunities and inflammation.

Much of the morbidity and mortality associated with persistent asthma is attributable to progressive and irreversible remodeling of the airway wall. Most theories concerning airway remodeling argue that the remodeling process is triggered in response to inflammatory mediators and cytokines.

We hypothesize that airway remodeling is triggered in response to the mechanical stress imposed on the airway epithelium during bronchoconstriction.

We use a compressive in vitro model system (Figure 1). In this system, primary human bronchial epithelial cells are grown in an air-liquid interface (ALI) culture and subjected to compressive stress, which is modeled through the application of a transepithelial pressure gradient at a magnitude of 20 to 30 cm H2O. This magnitude of stress is similar to the magnitude that bronchoconstriction imposes on the airway epithelium, and is significantly higher than the magnitude experienced during normal breathing. The compressive in vitro system recapitulates many aspects of airway remodeling in the absence of inflammatory cells (Putting the Squeeze on Airway Epithelia, Park et al. Physiology. 2015).

The findings using the compressive in vitro system have already led to experiments in humans showing that methacholine-induced bronchoconstriction, in the absence of eosinophilic inflammation, can lead to collagen deposition under the epithelial monolayer, enhanced expression of TGF-*, and increased numbers of goblet cells - key aspects of airway remodeling. These experiments provide in vivo validation of our experimental approach.

A full understanding of the asthmatic response requires many different models; in vitro compressive model system highlights and isolates the effects of mechanical stress on airway epithelial cells. We also use mouse asthma models to verify the physiological effects of target molecules and to identify further mechanisms.

Research
The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
  1. R01HL148152 (FREDBERG, JEFFREY J) Aug 15, 2019 - Apr 30, 2023
    NIH
    Physics of bronchial epithelial unjamming
    Role: Co-PI

Bibliographic
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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PMC Citations indicate the number of times the publication was cited by articles in PubMed Central, and the Altmetric score represents citations in news articles and social media. (Note that publications are often cited in additional ways that are not shown here.) Fields are based on how the National Library of Medicine (NLM) classifies the publication's journal and might not represent the specific topic of the publication. Translation tags are based on the publication type and the MeSH terms NLM assigns to the publication. Some publications (especially newer ones and publications not in PubMed) might not yet be assigned Field or Translation tags.) Click a Field or Translation tag to filter the publications.
  1. O'Sullivan MJ, Phung TN, Park JA. Bronchoconstriction: a potential missing link in airway remodelling. Open Biol. 2020 12; 10(12):200254. PMID: 33259745.
    Citations:    Fields:    
  2. O'Sullivan MJ, Mitchel JA, Mwase C, McGill M, Kanki P, Park JA. In well-differentiated primary human bronchial epithelial cells, TGF-ß1 and TGF-ß2 induce expression of furin. Am J Physiol Lung Cell Mol Physiol. 2021 02 01; 320(2):L246-L253. PMID: 33174447.
    Citations: 2     Fields:    Translation:HumansCellsPHPublic Health
  3. Hao Y, Bates S, Mou H, Yun JH, Pham B, Liu J, Qiu W, Guo F, Morrow JD, Hersh CP, Benway CJ, Gong L, Zhang Y, Rosas IO, Cho MH, Park JA, Castaldi PJ, Du F, Zhou X. Genome-Wide Association Study: Functional Variant rs2076295 Regulates Desmoplakin Expression in Airway Epithelial Cells. Am J Respir Crit Care Med. 2020 11 01; 202(9):1225-1236. PMID: 32551799.
    Citations: 3     Fields:    Translation:HumansCells
  4. Mitchel JA, Das A, O'Sullivan MJ, Stancil IT, DeCamp SJ, Koehler S, Ocaña OH, Butler JP, Fredberg JJ, Nieto MA, Bi D, Park JA. In primary airway epithelial cells, the unjamming transition is distinct from the epithelial-to-mesenchymal transition. Nat Commun. 2020 10 07; 11(1):5053. PMID: 33028821.
    Citations: 7     Fields:    Translation:HumansCells
  5. Veerati PC, Mitchel JA, Reid AT, Knight DA, Bartlett NW, Park JA, Grainge CL. Airway mechanical compression: its role in asthma pathogenesis and progression. Eur Respir Rev. 2020 Sep 30; 29(157). PMID: 32759373.
    Citations: 1     Fields:    
  6. Hou M, Han J, Li G, Kwon MY, Jiang J, Emani S, Taglauer ES, Park JA, Choi EB, Vodnala M, Fong YW, Emani SM, Rosas IO, Perrella MA, Liu X. Multipotency of mouse trophoblast stem cells. Stem Cell Res Ther. 2020 02 13; 11(1):55. PMID: 32054514.
    Citations: 1     Fields:    Translation:AnimalsCells
  7. O'Sullivan MJ, Mitchel JA, Das A, Koehler S, Levine H, Bi D, Nagel ZD, Park JA. Irradiation Induces Epithelial Cell Unjamming. Front Cell Dev Biol. 2020; 8:21. PMID: 32117962.
    Citations: 4     
  8. Kiliç A, Ameli A, Park JA, Kho AT, Tantisira K, Santolini M, Cheng F, Mitchel JA, McGill M, O'Sullivan MJ, De Marzio M, Sharma A, Randell SH, Drazen JM, Fredberg JJ, Weiss ST. Mechanical forces induce an asthma gene signature in healthy airway epithelial cells. Sci Rep. 2020 01 22; 10(1):966. PMID: 31969610.
    Citations: 7     Fields:    Translation:HumansCells
  9. Kim JH, Pegoraro AF, Das A, Koehler SA, Ujwary SA, Lan B, Mitchel JA, Atia L, He S, Wang K, Bi D, Zaman MH, Park JA, Butler JP, Lee KH, Starr JR, Fredberg JJ. Unjamming and collective migration in MCF10A breast cancer cell lines. Biochem Biophys Res Commun. 2020 01 15; 521(3):706-715. PMID: 31699371.
    Citations: 4     Fields:    Translation:HumansCells
  10. Kim SH, Mitchel JA, McGill M, Cremona TP, Baek JW, Kasahara DI, Anathy V, Israel E, Park JA. Increased extracellular maspin levels after mechanical compression in vitro or allergen challenge in vivo. J Allergy Clin Immunol. 2019 10; 144(4):1116-1118.e4. PMID: 31228474.
    Citations: 3     Fields:    Translation:HumansAnimalsCells
  11. Barrios J, Kho AT, Aven L, Mitchel JA, Park JA, Randell SH, Miller LA, Tantisira KG, Ai X. Pulmonary Neuroendocrine Cells Secrete ?-Aminobutyric Acid to Induce Goblet Cell Hyperplasia in Primate Models. Am J Respir Cell Mol Biol. 2019 06; 60(6):687-694. PMID: 30571139.
    Citations: 9     Fields:    Translation:HumansAnimalsCells
  12. He S, Carman CV, Lee JH, Lan B, Koehler S, Atia L, Park CY, Kim JH, Mitchel JA, Park JA, Butler JP, Lu Q, Fredberg JJ. The tumor suppressor p53 can promote collective cellular migration. PLoS One. 2019; 14(2):e0202065. PMID: 30707705.
    Citations: 2     Fields:    Translation:HumansCells
  13. Park HR, O'Sullivan M, Vallarino J, Shumyatcher M, Himes BE, Park JA, Christiani DC, Allen J, Lu Q. Transcriptomic response of primary human airway epithelial cells to flavoring chemicals in electronic cigarettes. Sci Rep. 2019 02 01; 9(1):1400. PMID: 30710127.
    Citations: 27     Fields:    Translation:HumansCellsPHPublic Health
  14. Glass K, Thibault D, Guo F, Mitchel JA, Pham B, Qiu W, Li Y, Jiang Z, Castaldi PJ, Silverman EK, Raby B, Park JA, Yuan GC, Zhou X. Integrative epigenomic analysis in differentiated human primary bronchial epithelial cells exposed to cigarette smoke. Sci Rep. 2018 08 24; 8(1):12750. PMID: 30143676.
    Citations: 3     Fields:    Translation:HumansCells
  15. Grainge C, Park JA. Inflammatory insights into airway remodelling in asthma. Respirology. 2018 12; 23(12):1084-1085. PMID: 30129688.
    Citations:    Fields:    Translation:Animals
  16. Lan B, Mitchel JA, O'Sullivan MJ, Park CY, Kim JH, Cole WC, Butler JP, Park JA. Airway epithelial compression promotes airway smooth muscle proliferation and contraction. Am J Physiol Lung Cell Mol Physiol. 2018 11 01; 315(5):L645-L652. PMID: 30070589.
    Citations: 8     Fields:    Translation:HumansCells
  17. Atia L, Bi D, Sharma Y, Mitchel JA, Gweon B, Koehler S, DeCamp SJ, Lan B, Kim JH, Hirsch R, Pegoraro AF, Lee KH, Starr JR, Weitz DA, Martin AC, Park JA, Butler JP, Fredberg JJ. Geometric constraints during epithelial jamming. Nat Phys. 2018 Jun; 14:613-620. PMID: 30151030.
    Citations: 24     
  18. Atia L, Bi D, Sharma Y, Mitchel JA, Gweon B, A. Koehler S, DeCamp SJ, Lan B, Kim JH, Hirsch R, Pegoraro AF, Lee KH, Starr JR, Weitz DA, Martin AC, Park JA, Butler JP, Fredberg JJ. Geometric constraints during epithelial jamming. Nature Physics. 2018; 613-20.
  19. Panganiban RA, Sun M, Dahlin A, Park HR, Kan M, Himes BE, Mitchel JA, Iribarren C, Jorgenson E, Randell SH, Israel E, Tantisira K, Shore S, Park JA, Weiss ST, Wu AC, Lu Q. A functional splice variant associated with decreased asthma risk abolishes the ability of gasdermin B to induce epithelial cell pyroptosis. J Allergy Clin Immunol. 2018 11; 142(5):1469-1478.e2. PMID: 29330013.
    Citations: 20     Fields:    Translation:HumansCells
  20. Rosner SR, Pascoe CD, Blankman E, Jensen CC, Krishnan R, James AL, Elliot JG, Green FH, Liu JC, Seow CY, Park JA, Beckerle MC, Paré PD, Fredberg JJ, Smith MA. The actin regulator zyxin reinforces airway smooth muscle and accumulates in airways of fatal asthmatics. PLoS One. 2017; 12(3):e0171728. PMID: 28278518.
    Citations: 6     Fields:    Translation:HumansAnimalsCells
  21. Rosenblum Lichtenstein JH, Molina RM, Donaghey TC, Hsu YH, Mathews JA, Kasahara DI, Park JA, Bordini A, Godleski JJ, Gillis BS, Brain JD. Repeated Mouse Lung Exposures to Stachybotrys chartarum Shift Immune Response from Type 1 to Type 2. Am J Respir Cell Mol Biol. 2016 Oct; 55(4):521-531. PMID: 27148627.
    Citations: 5     Fields:    
  22. Park JA, Atia L, Mitchel JA, Fredberg JJ, Butler JP. Collective migration and cell jamming in asthma, cancer and development. J Cell Sci. 2016 09 15; 129(18):3375-83. PMID: 27550520.
    Citations: 28     Fields:    Translation:HumansAnimals
  23. Park JA, Fredberg JJ. Cell Jamming in the Airway Epithelium. Ann Am Thorac Soc. 2016 Mar; 13 Suppl 1:S64-7. PMID: 27027955.
    Citations: 4     Fields:    Translation:HumansAnimalsCells
  24. Park JA, Mitchel JA, Qazvini NT, Kim JH, Park CY, Butler JP, Israel E, Randell SH, Shore SA, Drazen JM, Fredberg JJ. Compressive Stress Causes an Unjamming Transition and an Epithelial-Mesenchymal Transition in the Airway Epithelium in Asthma. Ann Am Thorac Soc. 2016 Mar; 13 Suppl 1:S102. PMID: 27027941.
    Citations: 1     Fields:    
  25. Krishnan R, Park JA, Seow CY, Lee PV, Stewart AG. Cellular Biomechanics in Drug Screening and Evaluation: Mechanopharmacology. Trends Pharmacol Sci. 2016 Feb; 37(2):87-100. PMID: 26651416.
    Citations: 11     Fields:    Translation:Humans
  26. Pegoraro AF, Fredberg JJ, Park JA. Problems in biology with many scales of length: Cell-cell adhesion and cell jamming in collective cellular migration. Exp Cell Res. 2016 04 10; 343(1):54-59. PMID: 26546401.
    Citations: 7     Fields:    Translation:HumansAnimals
  27. Park JA, Kim JH, Bi D, Mitchel JA, Qazvini NT, Tantisira K, Park CY, McGill M, Kim SH, Gweon B, Notbohm J, Steward R, Burger S, Randell SH, Kho AT, Tambe DT, Hardin C, Shore SA, Israel E, Weitz DA, Tschumperlin DJ, Henske EP, Weiss ST, Manning ML, Butler JP, Drazen JM, Fredberg JJ. Unjamming and cell shape in the asthmatic airway epithelium. Nat Mater. 2015 Oct; 14(10):1040-8. PMID: 26237129.
    Citations: 89     Fields:    Translation:HumansCells
  28. Park JA, Fredberg JJ, Drazen JM. Putting the Squeeze on Airway Epithelia. Physiology (Bethesda). 2015 Jul; 30(4):293-303. PMID: 26136543.
    Citations: 14     Fields:    Translation:HumansAnimalsCells
  29. Kim JH, Serra-Picamal X, Tambe DT, Zhou EH, Park CY, Sadati M, Park JA, Krishnan R, Gweon B, Millet E, Butler JP, Trepat X, Fredberg JJ. Propulsion and navigation within the advancing monolayer sheet. Nat Mater. 2013 Sep; 12(9):856-63. PMID: 23793160.
    Citations: 68     Fields:    Translation:AnimalsCells
  30. Park JA, Sharif AS, Shiomi T, Kobzik L, Kasahara DI, Tschumperlin DJ, Voynow J, Drazen JM. Human neutrophil elastase-mediated goblet cell metaplasia is attenuated in TACE-deficient mice. . 2013 May 15; 304(10):L701-7. PMID: 23564510.
    Citations: 8     Translation:HumansAnimalsCells
  31. Park JA, Sharif AS, Tschumperlin DJ, Lau L, Limbrey R, Howarth P, Drazen JM. Tissue factor-bearing exosome secretion from human mechanically stimulated bronchial epithelial cells in vitro and in vivo. J Allergy Clin Immunol. 2012 Dec; 130(6):1375-83. PMID: 22828416.
    Citations: 42     Fields:    Translation:HumansCells
  32. Marinkovic A, Mih JD, Park JA, Liu F, Tschumperlin DJ. Improved throughput traction microscopy reveals pivotal role for matrix stiffness in fibroblast contractility and TGF-ß responsiveness. . 2012 Aug 01; 303(3):L169-80. PMID: 22659883.
    Citations: 58     Translation:HumansCells
  33. Shiomi T, Tschumperlin DJ, Park JA, Sunnarborg SW, Horiuchi K, Blobel CP, Drazen JM. TNF-a-converting enzyme/a disintegrin and metalloprotease-17 mediates mechanotransduction in murine tracheal epithelial cells. Am J Respir Cell Mol Biol. 2011 Aug; 45(2):376-85. PMID: 21097655.
    Citations: 16     Fields:    Translation:AnimalsCells
  34. Park JA, Drazen JM, Tschumperlin DJ. The chitinase-like protein YKL-40 is secreted by airway epithelial cells at base line and in response to compressive mechanical stress. J Biol Chem. 2010 Sep 24; 285(39):29817-25. PMID: 20650887.
    Citations: 32     Fields:    Translation:HumansCells
  35. Kojic N, Chung E, Kho AT, Park JA, Huang A, So PT, Tschumperlin DJ. An EGFR autocrine loop encodes a slow-reacting but dominant mode of mechanotransduction in a polarized epithelium. FASEB J. 2010 May; 24(5):1604-15. PMID: 20056713.
    Citations: 13     Fields:    Translation:HumansCells
  36. Park JA, Tschumperlin DJ. Chronic intermittent mechanical stress increases MUC5AC protein expression. Am J Respir Cell Mol Biol. 2009 Oct; 41(4):459-66. PMID: 19168703.
    Citations: 34     Fields:    Translation:HumansCells
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Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.