Raghu R. Chivukula, MD PhD
A major current challenge in mammalian biology is deeply understanding the cell biology and biochemistry of the many specialized cells which create a human organism and cause disease. Doing so at a mechanistic level has been difficult because, until recently, the ability to grow and manipulate non-transformed differentiated cells in vitro has been limited. However, the ability to generate and manipulate complex tissues in vitro through organoid technologies opens the door to applying the tools of cutting-edge molecular biology and biochemistry to intact human tissues.
Through air-liquid interface culturing, we can generate human airway epithelium in the laboratory from healthy donor or patient airway stem cells. We applied this technology alongside modern molecular biology and imaging techniques to unravel the biological basis of a previously uncharacterized genetic lung disease. This image depicts human airway grown in a dish from 2 donors – the first a normal person (red) and the second (green) a patient with a severe genetic lung disease which we isolated to a problem with the development of cilia.