After a 21-year tenure in the Surgery Branch of the National Cancer Institute, National Institutes of Health, she joined the Johns Hopkins faculty in June 2006 to lead the newly-established Melanoma Program in the Kimmel Cancer Center. She has published over 100 original research articles and reviews on cancer immunology, and is internationally recognized for this work. Topalian's basic studies of human anti-tumor immune responses have provided a foundation for the translational development of immunotherapies for melanoma and other cancers.