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Gang Chen, PhD

Assistant Professor

Specialty Areas:

Lung stem/progenitor cells, airway mucins and inflammation in health and diseases.

About:

Dr. Gang Chen is an assistant professor in the Marsico Lung Institute and Cystic Fibrosis Research Center. He is also affiliated with the faculty of the Division of Pediatric Pulmonology at the Department of Pediatrics, Cell Biology and Physiology (CBP) Curriculum and the Biological & Biomedical Sciences Program (BBSP), ºÚÁÏÍø at Chapel Hill. Dr. Chen received his B.S. and M.S degrees both from Yangzhou University, China, his Ph.D. from the Molecular and Developmental Biology Graduate Program of Cincinnati Children’s Hospital, and his postdoctoral training from both the Cincinnati Children’s Hospital and Cystic Fibrosis Center of ºÚÁÏÍø at Chapel Hill.

Academic Experience & Training:

2021-±è°ù±ð²õ±ð²Ô³ÙÌýÌýAssistant Professor (Tenure Track)
Marsico Lung Institute/Cystic Fibrosis Research Center, University of North Carolina at Chapel Hill

2014-2020ÌýÌýÌýÌý Research Associate
Marsico Lung Institute/Cystic Fibrosis Research Center, University of North Carolina at Chapel Hill

2013-2014ÌýÌýÌýÌýÌýPostdoctoral Fellow
Cystic Fibrosis Research Center, University of North Carolina at Chapel Hill

2011-2012ÌýÌýÌýÌýÌýPostdoctoral Fellow
Perinatal Institute, Cincinnati Children’s Hospital

2004-2010     Graduate Student (PhD)
Molecular and Developmental Biology Graduate Program
Cincinnati Children’s Hospital and University of Cincinnati

2002-2003     Research Assistant
Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

1999-2002ÌýÌýÌýÌýÌýGraduate Student (MS)
College of Veterinary Medicine, Yangzhou University, Yangzhou, China

1995-1999ÌýÌýÌýÌýÌýUndergraduate Student (BS)
College of Bioscience and Biotechnology, Yangzhou University, Yangzhou, China

Honors & Awards:

2012-2013  American Lung Association Senior Research Training Fellowship

Research Experience:

Collection of immunohistochemistry images showing the expression of SPDEF and FOXA3 in healthy, COPD, and asthma cells
Figure 1: SPDEF and FOXA3 are expressed in the mucus-producing cells in the airways of COPD and asthma subjects. Figure is modified from Chen et al, 2014 AJRCCM.

Dr. Chen was trained as a molecular and developmental biologist during his PhD and an early postdoc training with Jeff Whitsett, MD, at Cincinnati Children’s Hospital Medical Center. Specifically, he studied the role of respiratory epithelial transcription factors in controlling lung branching morphogenesis, development, and roles of epithelial progenitor/stem cells during injury and repair. His thesis work resulted in the identification and explication of a number of important genes and a key transcription network including SPDEF, FOXA3 (Fig. 1,2), FOXA2 and NKX2.1, delineating their abilities to work as gateways that modulate MUC5AC expression and mucus production in airway goblet cells in response to Th2-dominant pulmonary inflammation that relates to allergic asthma and antiviral responses in the lung.

AB-PAS and immunofluorescent-staining images showing control cells and Spdef-expressing cells
Figure 2: SPDEF expression mediated by lentivirus led to increased mucus production, goblet cell differentiation, and MUC5AC/5B and ERN2 expression in the primary human bronchial epithelial cell cultures. Figure is modified from Chen et al, 2019 JCI.

Since joining the lab of Richard Boucher, MD, in the Marsico Lung Institute at ºÚÁÏÍø at Chapel Hill, Dr. Chen has been working to discover the transcriptional regulation of MUC5B, a major respiratory tract secretory mucin required at baseline for health, but often excessively produced in chronic muco-obstructive pulmonary diseases, like cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF), chronic bronchitis and chronic obstructive pulmonary disease (COPD). He and colleagues identified a novel pathway leading to excessive MUC5B production in the IPF lung that is mediated by the SPDEF-ERN2-XBP1S axis, linking the unfolded protein response (UPR) with mucin production in the distal airway epithelia of IPF (Fig. 3). Profoundly, this work for the first time explained the differential regulation of the MUC5B promoter polymorphism rs35705950, the strongest genetic association with pathogenesis of IPF, by the ER stress transcription factor XBP1S, a potential therapeutic target.

A figure composed of pictures comparing the cells of control and IPF subjects, as well as graphs demonstrating the expression of ERN2-XBP1S in IPF
Figure 3: ERN2-XBP1S axis is activated in distal airway epithelial cells in IPF lung where MUC5B is ectopically expressed. Figure is modified from Chen et al, 2019 AJRCCM.

Dr. Chen has also committed to study abnormal mucus hyperconcentration and obstruction in CF. He and colleagues have dissected the precise transcriptional mechanisms that regulate excessive mucin production in CF airways, dominated by non-TH2 inflammation that results in hyperproduction of regional-specific mucin expression patterns, i.e., MUC5AC/MUC5B-mixed in proximal vs. MUC5B-dominated in distal CF airways. They identified that proinflammatory and profibrotic cytokine interleukin 1β (IL1β) is the dominant factor presented in CF airway secretions that causes the abnormal mucus hyperconcentration phenotype in the CF lung. They developed genetic tools to block the function of IL1β receptor (IL1R1) to suppress excessive mucin production, as well as inflammatory responses by CRISPR-Cas9 technology or by the pharmacological inhibitor anakinra in primary human bronchial epithelial cells isolated from normal and CF lungs.

Microscopy pictures and graphs demonstrating the effect of CFTR defects in the Jobs lung
Figure 4: STAT3 mutations led to mucus obstruction, hyperconcentration, caused, at least in part, by reduced CFTR function in the bronchial epithelial cells.

In close collaboration with Drs. Richard Boucher and Kenneth Olivier at ºÚÁÏÍø, Drs. Alexandra Freeman and Kevin Fennelly at NIH, and Dr. Peter Mogayzel at John Hopkins, Dr. Chen has also led a study of the rare genetic disease autosomal dominant hyper-IgE syndrome (AD-HIES). AD-HIES is primarily an immunological disease, caused by mutations in the STAT3 protein which lead to IL22/TH17 cell differentiation deficiency, and it is often associated with recurrent pulmonary infection, the leading cause of mortality in this disease. Using primary patients’ airway cells, biopsy specimens, and STAT3 CRISPR/Cas9 gene-edited normal primary cells, this team has identified the molecular and cellular mechanisms underlying the STAT3 mutations caused mucociliary clearance defects and mucus obstruction (Fig. 4). These epithelial abnormalities lead to defective innate host defense and failure in clearance of infection, which in turn lead to chronic inflammation, lung structural damage and loss of lung function.

Selected Bibliography:

  1. Pickles RJ, Chen G, Randell SH. . J Clin Invest. 2024 Nov 1;134(21):e185689. doi: 10.1172/JCI185689. PMID: 39484717; PMCID: PMC11527439.
  2. 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. . Am J Respir Crit Care Med. 2024 Feb 15;209(4):374-389. doi: 10.1164/rccm.202306-1093OC. PMID: 38016030. PMCID: PMC10878387.
  3. Donoghue LJ, Markovetz MR, Morrison CB, Chen G, McFadden KM, Sadritabrizi T, Gutay MI, Kato T, Rogers TD, Snead JY, Livraghi-Butrico A, Button B, Ehre C, Grubb BR, Hill DB, Kelada SNP. . Am J Physiol Lung Cell Mol Physiol. 2023 Dec 1;325(6):L765-L775. doi: 10.1152/ajplung.00390.2022. PMID: 37847709. PMCID: PMC11068428.
  4. 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. . Sci Transl Med. 2023 Jun 7;15(699):eabo7728. doi: 10.1126/scitranslmed.abo7728. PMID: 37285404. PMCID: PMC10664029.
  5. Schworer SA, Chason KD, Chen G, Chen J, Zhou H, Burbank AJ, Kesic MJ, Hernandez ML. . J Allergy Clin Immunol. 2023 Jun;151(6):1577-1584.e4. doi: 10.1016/j.jaci.2023.01.015. PMID: 36708816. PMCID: PMC10257744.
  6. 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. . Am J Respir Crit Care Med. 2022 Dec 1;206(11):1336-1352. doi: 10.1164/rccm.202111-2606OC. PMID: 35816430. PMCID: PMC9746856.
  7. Hsu AP, Korzeniowska A, Aguilar CC, Gu J, Karlins E, Oler AJ, Chen G, Reynoso GV, Davis J, Chaput A, Peng T, Sun L, Lack JB, Bays DJ, Stewart ER, Waldman SE, Powell DA, Donovan FM, Desai JV, Pouladi N, Long Priel DA, Yamanaka D, Rosenzweig SD, Niemela JE, Stoddard J, Freeman AF, Zerbe CS, Kuhns DB, Lussier YA, Olivier KN, Boucher RC, Hickman HD, Frelinger J, Fierer J, Shubitz LF, Leto TL, Thompson III GR, Galgiani JN, Lionakis MS, Holland SM. . JCI Insight. 2022 Nov 22;7(22):e159491. doi: 10.1172/jci.insight.159491. PMID: 36166305. PMCID: PMC9746810.
  8. 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. . Am J Respir Crit Care Med. 2021 May 15;203(10):1275-1289. PMID: 33321047. PMCID: PMC8456462.
  9. 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. . Cell. 2020 Jul 23;182(2):429-446.e14. PMID: 32526206; PMCID: PMC7250779.
  10. Chen G, Sun L, Kato T, Okuda K, Martino MB, Abzhanova A, Lin JM, Gilmore RC, Batson B, Volmer AS, O’Neal YK, Dang H, Deng Y, Randell SH, Button B, Livraghi-Butrico A, Kesimer M, Ribeiro CMP, O’Neal WK, Boucher RC. . J Clin Invest. 2019 Oct 1;129(10):4433-4450. PMID: 31524632; PMCID: PMC6763234.
  11. 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. . Am J Respir Crit Care Med 2019 Jul 15;200(2):220-234. PMID: 30973754; PMCID: PMC6635783.
  12. 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. . Am J Respir Crit Care Med 2019 Mar 15;199(6):715-727. PMID: 30352166; PMCID: PMC6423099.
  13. 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. . Am J Respir Cell Mol Biol 2018; 59(3): 383-396. PMID: 29579396; PMCID: PMC6189647.
  14. Yu D, Saini Y, Chen G, Ghio AJ, Dang H, Burns KA, Wang Y, Davis RM, Randell SH, Esther CR, Jr., Paulsen F, Boucher RC. . Am J Pathol 2018; 188: 95-110. PMID: 29107074; PMCID: PMC5745530.
  15. Donoghue LJ, Livraghi-Butrico A, McFadden KM, Thomas JM, Chen G, Grubb BR, O’Neal WK, Boucher RC, Kelada SNP. . Genetics 2017; 207: 801-812. PMID: 28851744; PMCID: PMC5629340.
  16. Esther CR, Jr., Hill DB, Button B, Shi S, Jania C, Duncan EA, Doerschuk CM, Chen G, Ranganathan S, Stick SM, Boucher RC. . American journal of physiology Lung cellular and molecular physiology 2017; 312: L398-L404. PMID: 28062483; PMCID: PMC5374301.
  17. Rajavelu P, Chen G, Xu Y, Kitzmiller JA, Korfhagen TR, Whitsett JA. . J Clin Invest 2015; 125: 2021-2031. PMID: 25866971; PMCID: PMC4463206.
  18. Chen G, Korfhagen TR, Karp CL, Impey S, Xu Y, Randell SH, Kitzmiller J, Maeda Y, Haitchi HM, Sridharan A, Senft AP, Whitsett JA. . Am J Respir Crit Care Med 2014; 189: 301-313. PMID: 24392884; PMCID: PMC3977731.
  19. Ren X, Shah TA, Ustiyan V, Zhang Y, Shinn J, Chen G, Whitsett JA, Kalin TV, Kalinichenko VV. . Mol Cell Biol 2013; 33: 371-386. PMID: 23149934; PMCID: PMC3554115.
  20. Noah TK, Lo YH, Price A, Chen G, King E, Washington MK, Aronow BJ, Shroyer NF. . Gastroenterology 2013; 144: 1012-1023 e1016. PMID: 23376423; PMCID: PMC3738069.
  21. Marko CK, Menon BB, Chen G, Whitsett JA, Clevers H, Gipson IK. . Am J Pathol 2013; 183: 35-48. PMID: 23665202; PMCID: PMC3702735.
  22. Wang IC, Snyder J, Zhang Y, Lander J, Nakafuku Y, Lin J, Chen G, Kalin TV, Whitsett JA, Kalinichenko VV. . Mol Cell Biol 2012; 32: 3838-3850. PMID: 22826436; PMCID: PMC3457538.
  23. Korfhagen TR, Kitzmiller J, Chen G, Sridharan A, Haitchi HM, Hegde RS, Divanovic S, Karp CL, Whitsett JA. . Proc Natl Acad Sci U S A 2012; 109: 16630-16635. PMID: 23012424; PMCID: PMC3478616.
  24. Maeda Y, Chen G, Xu Y, Haitchi HM, Du L, Keiser AR, Howarth PH, Davies DE, Holgate ST, Whitsett JA. . Am J Respir Crit Care Med 2011; 184: 421-429. PMID: 21562130; PMCID: PMC3175541.
  25. Chen G, Wan H, Luo F, Zhang L, Xu Y, Lewkowich I, Wills-Karp M, Whitsett JA. . J Immunol 2010; 184: 6133-6141. PMID: 20483781.
  26. Chen G, Korfhagen TR, Xu Y, Kitzmiller J, Wert SE, Maeda Y, Gregorieff A, Clevers H, Whitsett JA. . J Clin Invest 2009; 119: 2914-2924. PMID: 19759516; PMCID: PMC2752084.
  27. Maeda Y, Suzuki T, Pan X, Chen G, Pan S, Bartman T, Whitsett JA. . J Biol Chem 2008; 283: 16084-16092. PMID: 18372249; PMCID: PMC2414293.
  28. Park K-S, Korfhagen TR, Bruno MD, Kitzmiller JA, Wan H, Wert SE, Khurana Hershey GK, Chen G, Whitsett JA. . J Clin Invest 2007; 117: 978-988. PMID: 17347682; PMCID: PMC1810569.

A full list of Gang Chen’s publication can be found at the following link:

Headshot of Gang Chen