Born in Perugia, Italy, and raised in the United States, Natale currently resides in New Mexico. Natale explores the links between art and activism and uses her art to inspire social change. She creates and directs large-scale art installations that engage thousands of artists, activists, and children to act on behalf of humanitarian causes. Natale believes that by inspiring action through art, the world can change, one person at a time.

In 2006, Natale conceived the Cradle Project, an art installation designed to represent the plight of millions of children orphaned by disease in Africa. The work raised financial support for community-based groups in Africa, helping to feed, shelter, and educate vulnerable children. Currently, Natale serves as the founding artist behind One Million Bones, a collaborative art installation designed to recognize the millions of individuals killed or displaced by ongoing genocides and mass atrocities in Sudan, the Democratic Republic of the Congo, and Burma. The project creates a visible movement to increase global awareness while raising funds needed to protect and aid displaced and vulnerable survivors. In the spring of 2013, all 1,000,000 bones will be installed on the National Mall in Washington.

Natale has received numerous awards, including a TED Global Fellowship and the Professional Achievement Award from the School of Arts and Humanities at Richard Stockton College of New Jersey. She served as an artist-in-residence at Columbia College of Chicago in 2008, 2010, and 2011. She speaks internationally about her installations and the topic of art and activism.