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She was a patient on House in the episode "Sleeping Dogs Lie" in 2006.
Mays has played the love interest of a character played by Masi Oka in two different roles: Charlie Andrews on Heroes and Nina in the direct-to-DVD film Get Smart's Bruce and Lloyd: Out of Control.
She has also been cast as a love interest twice for Glee co-star Matthew Morrison; in an unaired TV show called Nice Girls Don't Get the Corner Office, and as mysophobic guidance counsellor Emma Pillsbury on the Fox show Glee, which premiered on May 19, 2009.
She was part of the main cast of Glee for the first three seasons, then was made a guest star in seasons four, five, and six.
She starred in the spoof film Epic Movie and as Amy in Paul Blart: Mall Cop.She has also performed musical numbers on Glee including her solo performance of "Touch-a, Touch-a, Touch-a, Touch Me" from The Rocky Horror Show during the themed episode "The Rocky Horror Glee Show"; which was also the song she had sung for her audition for the role.In March 2010, Mays played Grace Winslow, the female lead in the live-action/animated film adaptation of The Smurfs.Blind Dating (also known as Blind Guy Driving) is a 2006 romantic comedy film directed by James Keach and starring Chris Pine, Eddie Kaye Thomas, Anjali Jay, Jane Seymour, and Jayma Mays.The film was produced by David Shanks and James Keach and distributed by Samuel Goldwyn Films LLC.