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She was raised on a small farm in New Jersey, daughter of Ruth Emma Hull Denis (a physician by training), and Thomas Laban Denis, an inventor, where she studied both Christian Science and theosophy. As a child, she learned exercises based on François Delsarte's Society Gymnastics and Voice Culture.
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While touring in Belasco's production of Madame DuBarry in 1904 her life was changed. She was at a drugstore with another member of Belasco's company in Buffalo, New York, when she saw a poster advertising Egyptian Deities cigarettes. The poster portrayed the Egyptian goddess Isis enthroned in a temple; this image captivated St. Denis on the spot and inspired her to create dances that expressed the mysticism that the goddess's image conveyed. From then on, St. Denis was immersed in Oriental philosophies.