Guillermo Romano Ibarra, M6G
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guillermo-romanoibarra@uiowa.edu
MSTP Learning Community: Flocks MSTP Entry Date: August 1, 2016 |
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PhD Program: Molecular Medicine |
Mentor: David Stoltz, MD, PhD |
| Graduate Profile | Lab Website |
Interrogating the role of Foxi1-expressing cells in human and pig airway epithelia
Mutations in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene lead to abnormal chloride and bicarbonate transport across epithelial surfaces throughout the body. It has been known that CFTR is not expressed homogenously in airway epithelia, but the precise understanding of this process remains unknown. Recent work has suggested that CFTR expression is limited to a specialized and rare group of cells termed Ionocytes, evolutionary homologs to well studied ionocytes found in Xenopus and Zebrafish that regulate epithelial ion exchange. In airway epithelia, these cells are characterized by high levels of CFTR, V-ATPase subunits, and are developmentally controlled by the transcription factor Foxi1. Ionocytes are hypothesized to express CFTR at such high levels that a few number of cells are primarily responsible for regulating the flow of ions across airway epithelia. My studies are investigating the role of ionocytes in healthy and diseased airway epithelia using a porcine model. Pig airway biology has been shown to closely replicate human airways in molecular, cellular, and physiological studies. To that end, our group has shown that CF pigs closely mimic human airway disease in CF. I hypothesize that modulation of the notch pathway, which regulates ionocytes development in xenopus and zebrafish, will alter the amount of Foxi1 epithelial expression in porcine cells and will allow us to investigate its role in regulating electrolyte transport. Pigs represent a strong model for physiological studies following induction or suppression of Foxi1 and the correlation it has with CF disease. Furthermore, a better understanding of the Foxi1 gene and promoter activity could provide important tools for use with viral vectors, which might contribute to the development of better gene therapy tools and approaches. Overall, these strategies may help us to better understand the role that ionocytes play in airway epithelia both during health and disease and provide important clues for therapeutic development.
Committees:
2016-2017 - MSTP Recruitment Committee
2016-2017 - MSTP Applicant Task Force
2022-present - MSTP Wellness Committee
Education:
2013 - BS, Biochemistry, Public Health - U of Washington
Publications:
Rehman T, Thornell IM, Pezzulo AA, Thurman AL, Romano Ibarra GS, Karp PH, Tan P, Duffey ME, Welsh MJ. TNFα and IL-17 alkalinize airway surface liquid through CFTR and pendrin. Am J Physiol Cell Physiol. 2020 Aug 1;319(2):C331-C344. doi: 10.1152/ajpcell.00112.2020. Epub 2020 May 20. PubMed PMID: 32432926; PubMed Central PMCID: PMC7500220.
Ostedgaard LS, Price MP, Whitworth KM, Abou Alaiwa MH, Fischer AJ, Warrier A, Samuel M, Spate LD, Allen PD, Hilkin BM, Romano Ibarra GS, Ortiz Bezara ME, Goodell BJ, Mather SE, Powers LS, Stroik MR, Gansemer ND, Hippee CE, Zarei K, Goeken JA, Businga TR, Hoffman EA, Meyerholz DK, Prather RS, Stoltz DA, Welsh MJ. Lack of airway submucosal glands impairs respiratory host defenses. Elife. 2020 Oct 7;9:e59653. doi: 10.7554/eLife.59653. PMID: 33026343; PMCID: PMC7541087.
Choi SH, Reeves RE, Romano Ibarra GS, Lynch TJ, Shahin WS, Feng Z, Gasser GN, Winter MC, Evans TIA, Liu X, Luo M, Zhang Y, Stoltz DA, Devor EJ, Yan Z, Engelhardt JF. Detargeting Lentiviral-Mediated CFTR Expression in Airway Basal Cells Using miR-106b. Genes (Basel). 2020 Oct 6;11(10). doi: 10.3390/genes11101169. PubMed PMID: 33036232; PubMed Central PMCID: PMC7601932.
Thurman AL, Li X, Villacreses R, Yu W, Gong H, Mather SE, Romano-Ibarra GS, Meyerholz DK, Stoltz DA, Welsh MJ, Thornell IM, Zabner J, Pezzulo AA. A Single-Cell Atlas of Large and Small Airways at Birth in a Porcine Model of Cystic Fibrosis. Am J Respir Cell Mol Biol. 2022 Mar 2. doi: 10.1165/rcmb.2021-0499OC. Epub ahead of print. PMID: 35235762.