Sherry Hsi carried out her first design experiment in1990 with Professor Alice Agogino and the NSF-sponsored Synthesis Engineering Education Coalition by studying the impact of multimedia case studies on learning. Realizing her background in engineering could only carry her so far in conducting learning research, she went back to graduate school in an interdisciplinary science education program at the University of California at Berkeley to learn more about cognition, social theories of learning, and innovative methods used by learning scientists. She performed studies in spatial reasoning mediated by software, studied how students learn from electronic discussion in science classes, and designed Internet-based curricula with Christopher Hoadley. Her research questions explored ways in which online social contexts could be designed to improve conceptual development in science and peer learning.

There were three main events that crystallized her interest in design experimentation. In 1993, Ann Brown wrote a paper about design experiments in the Journal of Learning Sciences that identified the weaknesses with psychological approaches to studying classroom learning mediated by technology. In 1994, as a delegate for Marcia Linn, she attended a National Design Experiments Consortium meeting held at Northwestern University and had the opportunity to meet Jan Hawkins and Allan Collins. That was also the first time she had met Iris Tabak and Bill Sandoval, both graduate students at Northwestern. In 1997, she was the recipient of an NSF traineeship in Science and Design. During the traineeship organized by Andy DiSessa and Marcia Linn, the class drafted the first "field guide" to design experiments along with colleagues Philip Bell and Christopher Hoadley. That same year, Sherry began collaborating with Robert Tinker at The Concord Consortium both designing large-scale online professional development and trying to understand how teachers develop new skills and knowledge in online communities of practice, extending her dissertation work from middle school students to online teachers.

In 1998-2000, Sherry collaborated with Eric Baumgartner and Sean Brophy as post-doctoral scholars with the Center for Innovative Learning Technologies. They investigated ways to foster "synergy", a collaborative-community approach to synthesizing research innovations across institutions to inform curricular design. She is the co-author of "Computers, Teachers, Peers: Science Learning Partners" which articulates pragmatic design principles based on longitudinal studies of computer-based science learning and teaching. Sherry is currently designing and studying online learning across different communities as the president and founder of Metacourse, an eLearning design company.