Hughes-Fulford trained in chemistry and biology before building a research career in molecular and cellular biology. Her scientific background led to her selection as a payload specialist for life-sciences research rather than the career astronaut corps.

On STS-40 in 1991, she worked aboard Columbia during Spacelab Life Sciences-1. The mission studied how spaceflight affects humans, animals, cells, and physiological systems, supporting later long-duration space medicine.

After her flight, Hughes-Fulford continued biomedical research, including work connected to bone, immune response, and the biological effects of microgravity. Her research remained relevant to human health both in space and on Earth.