SOX17 for the Treatment and Diagnosis of Lung Damage
Background
- The respiratory tract consists of an extensive epithelial cell surface that is in constant contact with gases, particles and pathogens from the outside environment.
- The lung needs to respond rapidly to damage from outside agents by repairing the epithelial surfaces involved in gas exchange, host defense and surfactant homeostasis.
- The pathways governing lung repair after damage are not well understood, but result in the rapid proliferation and differentiation of diverse cell types to preserve lung function.
- Dr. Jeff Whitsett and colleagues at the Cincinnati Children's Hospital Medical Center recently demonstrated that the Sox 17 gene is a key regulator mediating lung repair processes, and therefore presents a novel target for the diagnosis and treatment of lung damage.
Description of Current Technology
In a mouse model of lung injury, Dr. Whitsett's team demonstrated that ciliated, bronchiolar epithelial cells underwent a rapid squamous transdifferentiation after lung damage. These dedifferentiated cells proliferated and then redifferentiated into ciliated and non-ciliated cell types of the respiratory epithelium. The SOX 17 protein, a member of the High Mobility Group family of DNA binding proteins, was a key regulator governing the regeneration of the bronchiolar epithelium after lung damage. In transgenic mice, expression of SOX 17 in the lung was sufficient to induce ciliated and progenitor cell behavior in the fetal and adult lung. SOX 17 also activated the mouse Fox j1 promoter in an in vitro Hela cell reporter gene assay. Expression of B-catenin and Stat-3 coincided with SOX 17 expression and preceded the expression of transcription factors critical to lung epithelial cell differentiation including TTF-1, Fox a2 and Fox j1. A transcriptional program similar to that involved in normal lung morphogenesis coordinated squamous metaplasia and redifferentiation of progenitor cells following lung injury. Furthermore, this work has identified bronchiolar epithelial cells, previously thought to be terminally differentiated, as a source of progenitor cells that mediate lung repair. The invention describes novel methods for regulating SOX 17 to activate airway epithelial progenitor cell behavior for purposes of prophylaxis and/or treatment of lung damage. The invention also describes methods for detection of SOX 17 protein or mRNA as a diagnostic for pulmonary status.
Objective
Cincinnati Children's Research Foundation is seeking a commercial partner for the development and commercialization of this technology. A license or option agreement is available. A patent application has been filed.
Contact
We welcome any inquiries concerning this technology. To receive further confidential information, please contact:
Joseph D. Fondacaro, PhD
Director, Office of Intellectual Property and Venture Development
Cincinnati Children's Research Foundation
Mail Location 7032
3333 Burnet Avenue
Cincinnati, OH 45229-3039
Phone: 513-636-7695
Fax: 513-636-8453
Email: jdfonda@cchmc.org
Related Study Information
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