Mathieson researched T and B lymphocytes at Basel Institute for Immunology as a member from 1982 to 1983. From 1983 to 1989, she studied NK cells and T cell subsets as the head of a laboratory in the Biological Response Modifiers Program at the NCI-Frederick. Mathieson served as a program officer in the Vaccine Branch in the Division of AIDS in NIAID from 1989 to 1995.