Nicolino Valerio Valerio Dorrello, MD

In my clinical duties in the pediatric critical care unit, one of the most devastating and common injuries I come across, unfortunately, is severe, progressive lung injury. Despite current medical treatments, many of my young patients progress to chronic respiratory failure, leaving lung transplantation as the only definitive treatment. What represents a daily clinical challenge – making these patients better – has become my research passion: to find a therapeutic strategy to repair lungs early, before irreversible changes occur. My driving purpose is to help the children I see in intensive care to recover from severe lung injury and avoid the need for lung transplantation, so they can survive childhood and grow to have the fullest lives possible, free of chronic lung disease.

In the many different types of lung injury that I see, the primary tissue that is involved and injured is the lung epithelium. My overriding goal is to develop novel strategies to replace onlythe injured cells of the lung epithelium, while keeping the surrounding lung scaffold and vasculature intact. I recently succeeded in developing an airway-specific method to efficiently remove only the epithelium (de-epithelialization) while preserving lung vasculature and architecture in anex vivo rodent model. This new functional, vascularized lung graft then enabled the attachment and engraftment of lung epithelial progenitors (Science Advances, 2017). Prior to this breakthrough, earlier techniques to bioengineer functional lungs had been largely unsuccessful, as they attempted to use fully decellularized or synthetic scaffolds that lacked functional vasculature. My work shows that keeping the lung scaffold and vascular network intact and viable are critical for both maintaining the blood-gas barrier and for potentially guiding the growth and differentiation of exogenous lung progenitor cells towards a regeneration of healthy epithelium.

In summary, our work will define the optimal strategies to selectively removing defective lung epithelial cells and supportingthe proliferation and differentiation of lung progenitors towards healthy epithelium and ultimately lung repair.