BME PhD Dissertation Defense: Gabrielle (Gabby) Grifno

Title: "DEVELOPING AND UTILIZING THE CRYSTAL RIBCAGE PLATFORM TO PROBE RESPIRATORY AND CIRCULATORY FUNCTIONS OF THE LUNG FROM WHOLE ORGAN TO SINGLE ALVEOLUS IN HEALTH AND DISEASE"

Advisory Committee: Béla Suki, Ph.D. (Chair) Hadi T. Nia, Ph.D. (Advisor) Christopher C. Chen, M.D., Ph.D. Katrina Traber, M.D., Ph.D. Erin Crossey, M.D., Ph.D.

Abstract: Understanding pulmonary disease pathogenesis and therapeutic response requires probing the lung at cellular resolution during active respiration and circulation. However, real-time optical imaging of the intact lung has remained challenging due to the dynamic motion of the lung during physiological breathing and the delicate air-liquid interface. To address these challenges, we developed the “crystal ribcage”, a transparent ribcage that enables multiscale optical imaging of the functioning lung from the whole-organ to single-cell level. The crystal ribcage preserves the three-dimensional architecture, air–liquid interface, cellular diversity, and respiratory–circulatory functions of the lung while enabling controlled modulation of lung biophysics and immunity through intravascular, intrapulmonary, intraparenchymal, and optogenetic interventions. Using this platform in murine models of pulmonary disease, we directly visualized remodeling of respiratory and vascular transport processes at the level of individual alveoli and capillaries during disease progression.