Steven Brody, M.D.

Professor
Internal Medicine
Pulmonary & Critical Care Medicine

Molecular Cell Biology Program

  • 314-362-8969

  • 314-362-8968, 314-362-8920

  • 314-362-8987

  • 8052

  • CSRB 9938

  • brodys@wustl.edu

  • cilia, development, epithelium, lung, transcription

  • Molecular and genetic mechanisms of airway epithelial cell differentiation and ciliogenesis

Research Abstract:

The focus of our laboratory is abnormalities of the airway epithelial cell differentiation that characterize many lung diseases. We are particularly interested in mechanism of ciliogenesis in airway epithelial cells and primary and motile cilia in other tissues. To understand the molecular mechanisms that regulate normal pulmonary epithelial cell growth and differentiation in disease, we are investigating airway epithelial cell growth and differentiation in the developing lung, in a primary culture system of fully differentiated mouse airway epithelial cells that we developed, and lung infection models. We then use this information to determine normal pathways of differentiation and how these altered in disease and infection by respiratory viruses and bacteria.

Our work in ciliogenesis is built around the function of a master ciliogenesis transcription factor called Foxj1. This factor is a member of the forkhead family of transcription factors. We have generated a mouse that is deficient in this gene and found that the mouse has situs inversus and absent ciliogenesis, mimicking the human Kartegener`s syndrome and providing key information related to cilia biogenesis. Current genetic analyses are directed toward understanding the regulation of both primary and motile ciliogenesis and their relationships in development, differentiation, injury and repair of lung and other tissues.

Selected Publications:

Oltean A, Schaffer AJ, Bayly PV, Brody SL, Quantifying ciliary dynamics during assembly reveals step-wise waveform maturation in airway cells. Am J Respir Cell Mol Biol. 2018 May 31.

Horani A, Ustione A, Huang T, Firth AL, Pan J, Gunsten SP, Haspel JA, Piston DW, Brody SL, Establishment of the early cilia preassembly protein complex during motile ciliogenesis. Proc Nat Acad Sci 2018: online January 22, 2018 PMCID: (in progress).

Dickinson JD, Sweeter JM, Warren KJ, Ahmad IM, De Deken X, Zimmerman MC, Brody SL, Autophagy regulates DUOX1 localization and superoxide production in airway epithelial cells during chronic IL-13 stimulation. Redox Biology 2018: 14: 272-284.

Abid S, Xie S, Bose M, Shaul PW, Terada LS, Brody SL, Thomas PJ, Katzenellenbogen JA, Kim SH, Greenberg DE, Jain R, 17β-estradiol dysregulates innate immune responses to Pseudomonas aeruginosa respiratory infection and is modulated by estrogen receptor antagonism. Infect Immun 2017 Aug 7.

Dickinson J, Alevy Y, Malvin N, Patel K, Gunsten S, Holtzman M, Stappenbeck T, Brody SL, IL13 activates autophagy to regulate secretion in airway epithelial cells. Autophagy 2016: 12(2): 397-409. PMCID: PMC4835964

Horani A, Ferkol TW, Dutcher SK, Brody SL, Genetics and Biology of Primary Ciliary Dyskinesia. Paediatr Respir Rev. 2016 Mar: 18: 18-24. doi: 10.1016/j.prrv.2015.09.001. Epub 2015 Sep 11.

Pan J, Adair-Kirk T, Patel AC, Huang T, Yozamp N, Xu J, Reddy EP, Byers DE, Pierce RA, Holtzman MJ, Brody SL, Myb permits multilineage airway epithelial cell differentiation. Stem Cells 2014 Dec: 32(12): 3245-56. PMCID: PMC4245327

Horani A, Brody SL, Ferkol TW, Shoseyov D, Wasserman MG, Ta-shma A, Wilson KS, Bailey PV, Amirav I, Cohen-Cymberknoh M, Dutcher SK, Elpeleg O, Kerem E, CCDC65 mutation causes primary ciliary dyskinesia with normal ultrastructure and hyperkinetic cilia. PLoS One 2013: 8(8): e72299. PMCID: PMC3753302

Byers DE, Alexander-Brett J, Patel AC, Agapov E, Dang-Vu G, Jin X, Wu K, You Y, Alevy Y, Budelsky A, Brody SL, Pierce RA, Holtzman MJ, Long-term IL-33-producing epithelial progenitor cells in chronic obstructive lung disease. J Clin Invest 2013: 123: 3967-82. PMCID: PMC3754239

Horani A, Nath A, Wasserman MG, Huang T, Brody SL, Rho Kinase inhibition enhances airway epithelial cell proliferation, and efficiency of lentivirus transfection. Am J Respir Cell Mol Biol 2013: 49(3): 341-7. PMCID: PMC3824057

Last Updated: 7/27/2018 11:09:27 AM

Ciliogenesis in airway epithelial cells
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