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The principal function of the lung is to facilitate the absorption of oxygen and elimination of carbon dioxide necessary for lung development. This exchange occurs principally at the level of the alveolus. Premature birth often impairs alveolar formation and lung injury can reduce the number of alveoli. Our laboratory is focused on understanding the mechanism which governs alveolar growth and regeneration and how the pulmonary vasculature grows and remodels to maximize ventilation/perfusion matching.
Our laboratory is specifically focused on how lung matrix remodeling influences alveolar growth and pulmonary vascular morphogenesis. Our preliminary data suggested a role for a novel serine protease, Chymotrypsin-like elastase-1 (CELA1). Murine lung CELA1 was dynamically expressed during both lung development and compensatory lung regrowth following pneumonectomy. CELA1 expression was reduced in hyperoxia, an accepted model of impaired alveolar development. Elastase inhibition and silencing of CELA1 impairs angiogenesis in vitro. CELA1 was expressed in areas of elastin remodeling by in situ zymography. A transgenic mouse with LacZ reporter and the conditional potential is currently in development.
Our laboratory is also interested in how the pulmonary arterial matrix remodels in response to increased blood flow. We have demonstrated changes in right pulmonary arterial elastin structure following left pneumonectomy and are currently analyzing Next Generation mRNA sequencing data to determine mechanism and developing a model for measuring right pulmonary arterial compliance following pneumonectomy.
Cornett B, Snowball J, Varisco BM, Lang R, Whitsett J, Sinner D. Wntless is required for peripheral lung differentiation and pulmonary vascular development.Dev Biol. 2013 Mar 21. doi:pii: S0012-1606(13)00139-5.
Varisco BM. The pharmacology of acute lung injury in sepsis.Adv Pharmacol Sci. 2011:254619. 2011.
Wong HR, Cvijanovich NZ, Allen GL, Thomas NJ, Freishtat RJ, Anas N, Meyer K, Checchia PA, Lin R, Shanley TP, Bigham MT, Wheeler DS, Doughty LA, Tegtmeyer K, Poynter SE, Kaplan JM, Chima RS, Stalets E, Basu RK, Varisco BM, Barr FE. Validation of a gene expression-based subclassification strategy for pediatric septic shock.Crit Care Med. Nov;39(11):2511-7. 2011.
Sanders YY, Tollefsbol TO, Varisco BM, Hagood JS. Epigenetic regulation of thy-1 by histone deacetylase inhibitor in rat lung fibroblasts.Am J Respir Cell Mol Biol. Jul;45(1):16-23. 2011.
Brian M Varisco MDDivision of Critical Care MedicineCincinnati Children's Hospital Medical Center3333 Burnet AvenueCincinnati, OH 45229-3039
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