大象传媒

Skip to main content

Lawrence Ostrowski, PhD

Professor

Specialty Areas:

Structure and Function of Cilia; Diseases of Cilia and Mucociliary Clearance; Gene Therapy of CF and Primary Ciliary Dyskinesia

Research Focus:

The overall focus of research in my laboratory is to improve the diagnosis and treatment of airway diseases, especially those that result from impaired mucociliary clearance. Mucociliary clearance is the process by which inhaled pathogens and particulate matter are swept out of the lungs by the coordinated beating of the cilia that line the airways (Figure 1). In particular, our efforts focus on the diseases cystic fibrosis and primary ciliary dyskinesia, two inherited diseases caused by mutations that impair mucociliary clearance and lead to recurrent lung infections. The work in our laboratory ranges from basic studies of ciliated cells and the proteins that make up the complex structure of the motile cilia (Figure 2), to translational studies of new drugs and gene therapy vectors. Our laboratory uses a number of model systems, including traditional and inducible animal models, in vitro culture of differentiated mouse and human airway epithelial cells, and direct studies of human tissues. We also use a wide range of experimental techniques, from studies of RNA expression and proteomics to measuring ciliary activity in cultured cells and whole animals.

Electron micrograph image of human cilia
Figure 1a. An electron micrograph of human cilia. Photograph courtesy of Kimberly Burns, CF Center Histology Core Director.
Cartoon diagram and electron micrograph image of a cross-section through a cilium.
Figure 1b. Diagram and an electron micrograph of a cross-section through a cilium, illustrating the basic 鈥�9+2鈥� structure of axonemal doublets. Note the dynein arms that provide the force for ciliary motility.
Cartoon schematic of a single dynein arm at the protein level
Figure 1c. A schematic of a single dynein arm at the protein level, showing some of the more than 300 proteins required to assemble a cilium. Proteins highlighted in red are mutated in some cases of primary ciliary dyskinesia.

Selected Bibliography:

  1. Beaman MM, Yin W, Smith AJ, Sears PR, Leigh MW, Ferkol TW, Kearney B, Olivier KN, Kimple AJ, Clarke S, Huggins E, Nading E, Jung SH, Iyengar AK, Zou X, Dang H, Barrera A, Majoros WH, Rehder CW, Reddy TE, Ostrowski LE, Allen AS, Knowles MR, Zariwala MA, Crawford GE. . Am J Med Genet A. 2025 Feb;197(2):e63880. doi: 10.1002/ajmg.a.63880. PMID: 39364610. PMCID: PMC11698635.
  2. Tsuruta JK, Sears PR, Rebuli ME, Weitz AS, Durham PG, Clapp PW, Hill DB, Ostrowski LE, Dayton PA, Caughey MC. . Sci Rep. 2024 Dec 1;14(1):29840. doi: 10.1038/s41598-024-80933-x. PMID: 39617759; PMCID: PMC11609298.
  3. Dougherty GW, Ostrowski LE, N枚the-Menchen T, Raidt J, Schramm A, Olbrich H, Yin W, Sears PR, Dang H, Smith AJ, Beule AG, Hjeij R, Rutjes N, Haarman EG, Maas SM, Ferkol TW, Noone PG, Olivier KN, Bracht DC, Barbry P, Zaragosi LE, Fierville M, Kliesch S, Wohlgemuth K, K枚nig J, George S, Loges NT, Ceppe A, Markovetz MR, Luo H, Guo T, Rizk H, Eldesoky T, Dahlke K, Boldt K, Ueffing M, Hill DB, Pang YP, Knowles MR, Zariwala MA, Omran H. . Am J Respir Crit Care Med. 2024 Jul 1;210(1):63-76. doi: 10.1164/rccm.202308-1370OC. PMID: 38626355. PMCID: PMC11197063.
  4. Sears PR, Ostrowski LE. . Methods Mol Biol. 2024;2725:263-276. doi: 10.1007/978-1-0716-3507-0_17. PMID: 37856031.
  5. Yin W, Golliher HL, Ferguson AJ, Kimbell JS, Livraghi-Butrico A, Rogers TD, Grubb BR, Kimple AJ, Ostrowski LE. . Front Mol Biosci. 2023 Jul 24;10:1221796. doi: 10.3389/fmolb.2023.1221796. PMID: 37555015; PMCID: PMC10405821.
  6. Smith AJ, Bustamante-Marin XM, Yin W, Sears PR, Herring LE, Dicheva NN, L贸pez-Gir谩ldez F, Mane S, Tarran R, Leigh MW, Knowles MR, Zariwala MA,聽Ostrowski LE.听. J Cell Sci. 2022 Mar 15;135(6):jcs259512. doi: 10.1242/jcs.259512. PMID: 35178554. PMCID: PMC8995097.
  7. Rogers TD, Button B, Kelada SNP, Ostrowski LE, Livraghi-Butrico A, Gutay MI, Esther CR Jr, Grubb BR. . Front Physiol. 2022 Mar 9;13:842592. doi: 10.3389/fphys.2022.842592. PMID: 35356083; PMCID: PMC8959816.
  8. Ostrowski LE, Yin W, Smith AJ, Sears PR, Bustamante-Marin XM, Dang H, Hildebrandt F, Daniels LA, Capps NA, Sullivan KM, Leigh MW, Zariwala MA, Knowles MR. . Int J Mol Sci. 2022 Feb 3;23(3):1753. doi: 10.3390/ijms23031753. PMID: 35163670; PMCID: PMC8835943.
  9. Kato T, Mikami Y, Sun L, Rogers TD, Grubb BR, Morrison CB, Ehre C, Sears PR,聽Ostrowski LE, Randell SH, Boucher RC.听. Am J Respir Cell Mol Biol. 2021 Jun;64(6):760-764. doi: 10.1165/rcmb.2021-0033LE. PMID: 33788673.听PMCID: PMC8456889.
  10. Zhao Y, Pinskey J, Lin J, Yin W, Sears PR, Daniels LA, Zariwala MA, Knowles MR, Ostrowski LE, Nicastro D. . Mol Biol Cell. 2021 Jun 1;32(12):1202-1209. doi: 10.1091/mbc.E20-12-0806. PMID: 33852348. PMCID: PMC8351563.
  11. 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鈥橬eal YK, Minnick CE, Chua M, Quinney NL, Gentzsch M, Anderson CW, Ghio A, Matsui H, Nagase T,聽Ostrowski LE, Grubb BR, Olsen JC, Randell SH, Stripp BR, Tata PR, O鈥橬eal WK, Boucher RC.听. Am J Respir Crit Care Med.听2021 May 15;203(10):1275-1289. doi: 10.1164/rccm.202008-3198OC. PMID: 33321047.听PMCID: PMC8456462.
  12. Sears PR, Bustamante-Marin XM, Gong H, Markovetz MR, Superfine R, Hill DB, Ostrowski LE. . Biophys J. 2021 Apr 20;120(8):1387-1395. doi: 10.1016/j.bpj.2021.01.041. PMID: 33705757. PMCID: PMC8105732.
  13. Lee L,聽Ostrowski LE.听. Cell Mol Life Sci.听2021 Feb;78(3):769-797. doi: 10.1007/s00018-020-03633-5. PMID: 32915243.听PMCID: PMC7902362.
  14. Bustamante-Marin XM, Shapiro A, Sears PR, Charng WL, Conrad DF, Leigh MW, Knowles MR, Ostrowski LE, Zariwala MA. . J Hum Genet. 2020 Jan;65(2):175-180. doi: 10.1038/s10038-019-0686-1. PMID: 31636325. PMCID: PMC6920546.
  15. Yin W, Livraghi-Butrico A, Sears PR, Rogers TD, Burns KA, Grubb BR, Ostrowski LE. . Am J Respir Cell Mol Biol. 2019 Sep;61(3):312-321. doi: 10.1165/rcmb.2017-0387OC. PMID: 30896965. PMCID: PMC6839924.
  16. Bustamante-Marin XM, Yin WN, Sears PR, Werner ME, Brotslaw EJ, Mitchell BJ, Jania CM, Zeman KL, Rogers TD, Herring LE, Refab茅rt L, Thomas L, Amselem S, Escudier E, Legendre M, Grubb BR, Knowles MR, Zariwala MA, Ostrowski LE. Am J Hum Genet. 2019 Feb 7;104(2):229-245. doi: 10.1016/j.ajhg.2018.12.009. PMID: 30665704. PMCID: PMC6372263.
  17. Rogers TD, Ostrowski LE, Livraghi-Butrico A, Button B, Grubb BR. Sci Rep. 2018 Oct 3;8(1):14744. doi: 10.1038/s41598-018-33053-2. PMID: 30282981. PMCID: PMC6170422.
  18. Rosenfeld M, Ostrowski LE, Zariwala MA. Thorax. 2018 Feb;73(2):101-102. doi: 10.1136/thoraxjnl-2017-210776. PMID: 29133352. PMCID: PMC6040643.
  19. Blackmon R, Kreda S, Sears P, Chapman B, Hill DB, Tracy J, Ostrowski L, Oldenburg A. Nanoscale. 2017 Apr 13;9(15):4907-17. doi: 10.1039/c7nr00376e. PMID: 28358158. PMCID: PMC5473168.
  20. Blackburn K, Bustamante-Marin X, Yin W, Goshe MB, Ostrowski LE. J Proteome Res. 2017 Apr 7;16(4):1579-1592. doi: 10.1021/acs.jproteome.6b00972. PMID: 28282151. PMCID: PMC5733142.
  21. Bustamante-Marin XM, Ostrowski LE. Cold Spring Harb Perspect Biol. 2017 Apr 3;9(4). doi: 10.1101/cshperspect.a028241. PMID: 27864314. PMCID: PMC5378048.
  22. Barrick J, Doblas A, Gardner MR, Sears PR, Ostrowski LE, Oldenburg AL. Opt Lett. 2016 Dec 15;41(24):5620-5623. doi: 10.1364/OL.41.005620. PMID: 27973473. PMCID: PMC5235345.
  23. Grubb BR, Livraghi-Butrico A, Rogers TD, Yin W, Button B, Ostrowski LE. Am J Physiol Lung Cell Mol Physiol. 2016 May 1;310(9):L860-7. doi: 10.1152/ajplung.00015.2016. PMID: 26968767. PMCID: PMC4867354.
  24. Turner MJ, Matthes E, Billet A, Ferguson AJ, Thomas DY, Randell SH, Ostrowski LE, Abbott-Banner K, Hanrahan JW. Am J Physiol Lung Cell Mol Physiol. 2016 Jan 1;310(1):L59-70. doi: 10.1152/ajplung.00324.2015. PMID: 26545902.
  25. Blackmon RL, Kreda SM, Sears PR, Ostrowski LE, Hill DB, Chapman BS, Tracy JB, Oldenburg AL. Proc SPIE Int Soc Opt Eng. 2016;9697. PMID: 27746581. PMCID: PMC5061133.
  26. Sears PR, Yin WN, Ostrowski LE. Am J Physiol Lung Cell Mol Physiol. 2015 Jul 15;309(2):L99-108. doi: 10.1152/ajplung.00024.2015. PMID: 25979076. PMCID: PMC4504973.
  27. Lin J, Yin W, Smith MC, Song K, Leigh MW, Zariwala MA, Knowles MR, Ostrowski LE, Nicastro D. Nat Commun. 2014 Dec 4;5:5727. doi: 10.1038/ncomms6727. PMID: 25473808; PMCID: PMC4267722.
  28. Knowles MR, Ostrowski LE, Leigh MW, Sears PR, Davis SD, Wolf WE, Hazucha MJ, Carson JL, Olivier KN, Sagel SD, Rosenfeld M, Ferkol TW, Dell SD, Milla CE, Randell SH, Yin W, Sannuti A, Metjian HM, Noone PG, Noone PJ, Olson CA, Patrone MV, Dang H, Lee HS, Hurd TW, Gee HY, Otto EA, Halbritter J, Kohl S, Kircher M, Krischer J, Bamshad MJ, Nickerson DA, Hildebrandt F, Shendure J, Zariwala MA. Am J Respir Crit Care Med. 2014 Mar 15;189(6):707-17. doi: 10.1164/rccm.201311-2047OC. PMID: 24568568; PMCID: PMC3983840.
  29. Knowles MR, Ostrowski LE, Loges NT, Hurd T, Leigh MW, Huang L, Wolf WE, Carson JL, Hazucha MJ, Yin W, Davis SD, Dell SD, Ferkol TW, Sagel SD, Olivier KN, Jahnke C, Olbrich H, Werner C, Raidt J, Wallmeier J, Pennekamp P, Dougherty GW, Hjeij R, Gee HY, Otto EA, Halbritter J, Chaki M, Diaz KA, Braun DA, Porath JD, Schueler M, Baktai G, Griese M, Turner EH, Lewis AP, Bamshad MJ, Nickerson DA, Hildebrandt F, Shendure J, Omran H, Zariwala MA. Am J Hum Genet. 2013 Oct 3;93(4):711-20. doi: 10.1016/j.ajhg.2013.07.025. PMID: 24055112; PMCID: PMC3791252.
  30. Knowles MR, Leigh MW, Ostrowski LE, Huang L, Carson JL, Hazucha MJ, Yin W, Berg JS, Davis SD, Dell SD, Ferkol TW, Rosenfeld M, Sagel SD, Milla CE, Olivier KN, Turner EH, Lewis AP, Bamshad MJ, Nickerson DA, Shendure J, Zariwala MA; Genetic Disorders of Mucociliary Clearance Consortium. Am J Hum Genet. 2013 Jan 10;92(1):99-106. doi: 10.1016/j.ajhg.2012.11.003. PMID: 23261302; PMCID: PMC3542458.
  31. Grubb BR, O’Neal WK, Ostrowski LE, Kreda SM, Button B, Boucher RC. Am J Physiol Lung Cell Mol Physiol. 2012 Jan 15;302(2):L238-47. doi: 10.1152/ajplung.00083.2011. PMID: 22003093; PMCID: PMC3349361.
  32. Ostrowski LE, Yin W, Rogers TD, Busalacchi KB, Chua M, O’Neal WK, Grubb BR. Am J Respir Cell Mol Biol. 2010 Jul;43(1):55-63. doi: 10.1165/rcmb.2009-0118OC. PMID: 19675306; PMCID: PMC2911571.
Headshot of Lawrence Ostrowski