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In 2015, Byrne co-starred with Melissa Mc Carthy, Jude Law and Jason Statham in the hit comedic action tale Spy, In 2016, Rebecca Skloot (author of The Immortal Life of Henrietta Lacks) announced that Byrne would be playing Skloot in the HBO film adaptation of her book.
The film will also star Oprah Winfrey and Reneé Elise Goldsberry.
Along with co-star Glenn Close, she appeared in all of the show's fifty-nine episodes.
Byrne has also starred in the films Troy, 28 Weeks Later, Knowing, Insidious, X-Men: First Class, X-Men: Apocalypse, as well as the comedies Get Him to the Greek, Bridesmaids, Neighbors, Neighbors 2: Sorority Rising, and Spy.
Cannavale was married to "Rachel Getting Married" screenwriter Jenny Lumet from 1994 to 2003.