In 1828 she professed as Sister Mary Angela, and began her work, mostly with orphan children.
In 1849, during the cholera epidemic, Hughes was assistant to the Mother General, Elizabeth Boyle.
She was then appointed to found St Vincent's Hospital in New York City, becoming its first superior.
She left this post in December 1855 when she was elected third mother general of her community.
In this post she moved the motherhouse to Riverdale in the Bronx,[1] and oversaw the opening of 15 schools and convents.