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Rose was born at Viterbo in Italy, the daughter of a doctor. Following the death of her fiancé she entered a convent, but soon returned home to care for her newly widowed mother. Meanwhile, Rose invited the women of the neighborhood to recite the rosary in her home, forming a sort of sodality with them.

As she looked to her future, Rose, under the spiritual guidance of a Jesuit priest, became convinced that she was called to become a teacher in the world rather than a contemplative nun in a convent. Clearly, she made the right choice: She was a born teacher, and the free school for girls she opened in 1685 was well received.

Soon the cardinal invited her to oversee the training of teachers and the administration of schools in his Diocese of Montefiascone. As Rose's reputation grew, she was called upon to organize schools in many parts of Italy, including Rome. Her disposition was right for the task as well, for Rose often met considerable opposition but was never deterred.

She died in Rome in 1728, where a number of miracles were attributed to her. She was beatified in 1952. The sodality, or group of women she had invited to prayer, was ultimately given the rank of a religious congregation. Today, the so-called Venerini Sisters can be found in the United States and elsewhere, working among Italian immigrants.