In 2010 she became a principal investigator and unit head at the National Institutes of Health with a primary appointment in the National Institute of Neurological Disorders and Stroke (NINDS) and a joint appointment in the Biochemistry and Biophysics Center at the National Heart, Lung and Blood Institute (NHLBI). In 2017 Roll-Mecak became a tenured Senior Investigator. Her work focuses on how the genetic (isoform variation) and chemical diversity (posttranslational modifications) of tubulin regulate the dynamics and mechanical properties of microtubules and constitutes a code that is interpreted by microtubule based motors and associated proteins. This code is also referred to as the "tubulin code.".