Some years ago, Ahmad Nabhan set out to control the most dangerous cell in the human body.
That’s what Nabhan and his advisor called a small community of pulmonary denizens known as alveolar type 2 cells. These cells are powerful, capable of both vast creation and destruction. They regenerate lung tissue after injury. But they also give rise to non-small cell lung cancer and idiopathic pulmonary fibrosis, two of America’s leading killers.
Nabhan knew none of this when he arrived as a Ph.D. student at Stanford in 2013, a Jordanian immigrant and would-be medical student who switched to research after working at a clinic in Hollywood and seeing what medicine looked like without good treatments. He decided he wanted to make better ones. He learned quickly, harnessing new techniques to identify a key subset of the alveolar cells they might target to regenerate cells when the lung is sick or injured.
These cells were controlled by WNT, a protein found across the human body and across life: “If you cut a flatworm in half, and it grows,” noted Nabhan, “that process is dependent on WNT.” The question was how do you target WNT in one cell but not others? Many had failed.
The answer: single-cell sequencing. Working at Genentech as a postdoc, Nabhan used the new technology to show that different cells had subtly different WNT receptors. That meant it might be possible to develop drugs activating only the alveolar type 2 cells needed for regeneration.
Trials are already underway. Nabhan, meanwhile, is interviewing, hoping for a job that will let him apply these principles beyond the lung.
“Organs are very different, but there are also themes,” he said. “They basically become diseased, very often in the same way. … By understanding the principles of tissue organization, we’ll come up with more informed approaches to treat diseases. But also at the same time, by understanding the principles and the differences, we’ll learn more biology.”
— Jason Mast