Donis-Keller has a B.Sc. and an H.B.Sc. from Lakehead University. She earned her Ph.D. at Harvard University under the direction of Walter Gilbert in 1979. After employment at the biotechnology companies Biogen and Collaborative Research, she joined the faculty at Washington University School of Medicine. In 2001, she earn an MFA in studio art from the School of the Museum of Fine Arts in Boston and Tufts University and she joined the faculty at the Olin College of Engineering. In 2012, she was named the Michael. E. Moody Faculty Chair.
Donis-Keller’s graduate research established a method to do RNA sequencing. During her time at Collaborative Research, her research group created the first genetic map of the human genome. Donis-Keller was unable to secure either NIH or venture funding for generating the RFLP map, but convinced Collaborative Research’s management to fund the project. She continued to work on the genetic linkage map and led research into understanding the genetic basis of cystic fibrosis,thyroid cancer, and breast cancer.