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The Odyssey STEM Academy curriculum, based on the National Academy of Engineering Grand Challenges, will engage scholars in society’s most challenging issues such as artificial intelligence, personalized medicine, and urban infrastructure renewal. The 14 challenges are clustered in four cross-cutting themes: Sustainability, Health, Security, and Joy of Living. Addressing the challenges will require scholars to apply a multidisciplinary approach to learning. They will read, write, think and behave like explorers, artists, inventors, and entrepreneurs with curiosity and creativity. They will lead with cultural competence and social consciousness and human-centered design solutions by first setting aside their own assumptions about the world to gain insight into their users and their needs.