Mackem undertook her graduate research on the regulation of herpes immediate early gene expression by VP16 with Bernard Roizman and received her Ph.D. as an MSTP trainee at the University of Chicago.

at the Johns Hopkins School of Medicine, and then went on to residency training in anatomic pathology at the National Cancer Institute (NCI).

Mackem serves as an attending anatomic pathologist for the Laboratory of Pathology and National Institutes of Health Clinical Center.

[2] Her research has focused on vertebrate primary axis formation and the regulation of patterning and differentiation during limb development.

Mackem studies limb development as a model for learning how signaling networks orchestrate the formation of a complex 3-dimensional structure, using combined genetic, genomic, and biochemical approaches to study transcription factors and signaling cascades that regulate the formation and pattern of digits and unravel the regulatory hierarchy between early patterning and digit morphogenesis.