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Kenichi Okuda, MD, PhD

Assistant Professor

Specialty Areas:

Pathophysiology of airway mucociliary clearance in health and disease, biology of human small airways.

Chronology:

Dr. Okuda obtained his M.D. degree from Yamagata University in Japan (2010), followed by residency training in internal medicine and fellowship in respiratory medicine. During the fellowship, he worked at Tokyo National Hospital, which was a 300-bed hospital for patients with respiratory diseases. Thereafter, he entered the graduate school of medicine at the University of Tokyo in Japan. In the second year of graduate school, he applied for postdoctoral training in Dr. Richard Boucher’s laboratory at The University of North Carolina (UNC) at Chapel Hill to engage in studies of airway and mucus biology. Using the study conducted at UNC at Chapel Hill, he earned his Ph.D. degree in medicine from The University of Tokyo (2019). After a 2-year period as a Research Associate, Dr. Okuda was promoted in 2021 to an Assistant Professor in the Department of Medicine, Division of Pulmonary Diseases and Critical Care Medicine at UNC at Chapel Hill.

Research Focus:

Dr. Okuda’s overall research interests focus on how the mucociliary clearance (MCC) system is regulated to maintain homeostasis in the lung and how it fails in muco-obstructive lung diseases, including CF. He particularly has a great interest in distinct regulatory mechanisms active in the MCC system in large versus small airways. Under Dr. Boucher’s supervision, he characterized the regional expression patterns of major airway secretory mucins, MUC5AC and MUC5B, in normal human airways (AJRCCM, 2019). Based on these research interests, his long-term career goal is to work, as a professional investigator, toward a full understanding of the MCC system in the lungs and contribute to the improvement of the prognosis in all patients with muco-obstructive lung diseases.

MUC5AC, MUC5B, and CCSP mRNA co-expression is region-specific in normal human airways. Submucosal glands (SMG) express MUC5B, but not MUC5AC (A). Both MUC5B and MUC5AC are colocalized in CCSP+ cells in proximal superficial epithelium (B), whereas MUC5B is colocalized in CCSP+ cells of distal airway superficial epithelia (C). In the terminal bronchioles, neither MUC5B nor MUC5AC was detected (D).

Selected Bibliography:

  1. 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.
  2. Okuda K, Randell SH, Birket SE. The Big Impact of Small Airway pH. Am J Respir Cell Mol Biol. 2021 Apr 8. doi: 10.1165/rcmb.2021-0070ED. Epub ahead of print. PMID: 33831321.
  3. Huang N, Pérez P, Kato T, Mikami Y, Okuda K, Gilmore RC, Conde CD, Gasmi B, Stein S, Beach M, Pelayo E, Maldonado JO, Lafont BA, Jang SI, Nasir N, Padilla RJ, Murrah VA, Maile R, Lovell W, Wallet SM, Bowman NM, Meinig SL, Wolfgang MC, Choudhury SN, Novotny M, Aevermann BD, Scheuermann RH, Cannon G, Anderson CW, Lee RE, Marchesan JT, Bush M, Freire M, Kimple AJ, Herr DL, Rabin J, Grazioli A, Das S, French BN, Pranzatelli T, Chiorini JA, Kleiner DE, Pittaluga S, Hewitt SM, Burbelo PD, Chertow D; NIH COVID-19 Autopsy Consortium; HCA Oral and Craniofacial Biological Network, Frank K, Lee J, Boucher RC, Teichmann SA, Warner BM, Byrd KM. SARS-CoV-2 infection of the oral cavity and saliva. Nat Med. 2021 Mar 25. doi: 10.1038/s41591-021-01296-8. Epub ahead of print. PMID: 33767405.
  4. Hou YJ, Chiba S, Halfmann P, Ehre C, Kuroda M, Dinnon KH 3rd, Leist SR, Schäfer A, Nakajima N, Takahashi K, Lee RE, Mascenik TM, Graham R, Edwards CE, Tse LV, Okuda K, Markmann AJ, Bartelt L, de Silva A, Margolis DM, Boucher RC, Randell SH, Suzuki T, Gralinski LE, Kawaoka Y, Baric RS. SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo. Science. 2020 Dec 18;370(6523):1464-1468. doi: 10.1126/science.abe8499. PMID: 33184236. PMCID: PMC7775736.
  5. Miyashita N, Horie M, Suzuki HI, Saito M, Mikami Y, Okuda K, Boucher RC, Suzukawa M, Hebisawa A, Saito A, Nagase T. FOXL1 Regulates Lung Fibroblast Function via Multiple Mechanisms. Am J Respir Cell Mol Biol. 2020 Dec;63(6):831-842. doi: 10.1165/rcmb.2019-0396OC. PMID: 32946266. PMCID: PMC8017595.
  6. Leist SR, Dinnon KH 3rd, Schäfer A, Tse LV, Okuda K, Hou YJ, West A, Edwards CE, Sanders W, Fritch EJ, Gully KL, Scobey T, Brown AJ, Sheahan TP, Moorman NJ, Boucher RC, Gralinski LE, Montgomery SA, Baric RS. A Mouse-Adapted SARS-CoV-2 Induces Acute Lung Injury and Mortality in Standard Laboratory Mice. Cell. 2020 Sep 23:S0092-8674(20)31247-2. doi: 10.1016/j.cell.2020.09.050. PMID: 33031744; PMCID: PMC7510428.
  7. 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. *Co-first authors. **Co-senior authors.
  8. 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.
  9. Chen G, Sun L, Kato T, Okuda K, Martino MB, Abzhanova A, Lin JM, Gilmore RC, Batson BD, Volmer AS, Dang H, Deng Y, Randell SH, Button B, Livraghi-Butrico A, Kesimer M, Ribeiro CMP, 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.
  10. 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.
  11. Okuda K, Chen G, Subramani DB, Wolf M, Gilmore RC, Kato T, Radicioni G, Kesimer M, Chua M, 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 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.
  12. Ando T, Kawashima M, Masuda K, Takeda K, Okuda K, Suzuki J, Ohshima N, Horibe M, Tamura A, Nagai H, Matsui H, Ohta K. Exacerbation of chronic pulmonary aspergillosis was associated with a high rebleeding rate after bronchial artery embolization. Respir Investig. 2019 May;57(3):260-267. doi: 10.1016/j.resinv.2018.12.009. PMID: 30692051.
  13. Kato T, Kobayashi K, Suzukawa M, Saito M, Okuda K, Koyama K, Igarashi S, Arakawa S, Ohshima N, Matsui H, Nagase T, Ohta K. Epithelial-mesenchymal transition of human lung adenocarcinoma A549 cells up-regulates cytokine production upon LPS stimulation. Allergol Int. 2017 Sep;66S:S56-S58. doi: 10.1016/j.alit.2017.06.014. PMID: 28712741.
  14. Ando T, Kawashima M, Masuda K, Takeda K, Okuda K, Suzuki J, Ohshima N, Matsui H, Tamura A, Nagai H, Akagawa S, Ohta K. Clinical and Angiographic Characteristics of 35 Patients With Cryptogenic Hemoptysis. Chest. 2017 Nov;152(5):1008-1014. doi: 10.1016/j.chest.2017.05.007. PMID: 28526654.
  15. Okuda K, Masuda K, Kawashima M, Ando T, Koyama K, Ohshima N, Tamura A, Nagai H, Akagawa S, Matsui H, Ohta K. Bronchial artery embolization to control hemoptysis in patients with Mycobacterium avium complex. Respir Investig. 2016 Jan;54(1):50-8. doi: 10.1016/j.resinv.2015.08.004. PMID: 26718145.
  16. Koyama K, Ohshima N, Suzuki J, Kawashima M, Okuda K, Sato R, Suzukawa M, Nagai H, Matsui H, Ohta K. Evaluation of clinical characteristics and prognosis of chronic pulmonary aspergillosis depending on the underlying lung diseases: Emphysema vs prior tuberculosis. J Infect Chemother. 2015 Nov;21(11):795-801. doi: 10.1016/j.jiac.2015.08.006. PMID: 26410549.
  17. Koyama K, Ohshima N, Kawashima M, Okuda K, Sato R, Nagai H, Matsui H, Ohta K. Characteristics of pulmonary Mycobacterium avium complex disease diagnosed later in follow-up after negative mycobacterial study including bronchoscopy. Respir Med. 2015 Oct;109(10):1347-53. doi: 10.1016/j.rmed.2015.08.016. PMID: 26365483.

A full list of Kenichi Okuda’s publication can be found at the following link: https://www.ncbi.nlm.nih.gov/myncbi/1fg8udpEgVZE1k/bibliography/public/

Kenichi Okuda, MD, PhD