Those autoimmune disorders include lupus and scleroderma, both of which affect the skin. Chang finds confronting such puzzles that arise in patients especially compelling. After earning his MD at Harvard Medical School, Chang moved across the country for his clinical residency in dermatology at Stanford. Skin fascinated him. He liked that he could actually see the manifestation of his patients’ underlying conditions. And he liked that skin still held so many mysteries. “Skin is different in every location – why do we have long hair on our scalp but not on our palms and soles? And how do skin cells know and remember where they are in the body?” he asks.
Investigating those questions has led Chang to sample skin collected from banks of frozen newborn foreskin and from cadavers at the morgue. That research has revealed a sort of global positioning system for the body’s cells.
Chang’s work with patients has also taken him back to those uncharted regions of the genome.
His team recently discovered, for example, that our genome’s dark matter explained why a drug treatment for skin cell lymphoma worked in only about 20 percent of patients. “It was a black box,” he says. “But now we have an idea about what is happening.”