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In October 2011, Dern starred in a new HBO television series called Enlightened.
Dern plays Amy Jellicoe, "a health and beauty executive who returns from a post-meltdown retreat to pick up the pieces of her broken life" with, among others, her mother, played by her real-life mother Ladd.
In 1997, Dern was featured in Widespread Panic's music video for their song, "Aunt Avis", which was directed by Dern's then boyfriend and future fiancé, Billy Bob Thornton.
In 1998, Dern co-starred in Jodie Foster's film The Baby Dance.
Dern's starring role in Blue Velvet was a breakthrough though her next notable film, Wild at Heart, took almost four years to be released.
Dern's affiliation with David Lynch has continued with her role in Inland Empire.
While dating Thornton in 1999, she was cast as his love interest in his film Daddy and Them, which also includes Diane Ladd.
She had a minor role in Jurassic Park III, and was a supporting actress in the film I Am Sam.She guest-starred on The West Wing, was a voice on King of the Hill, and was a lesbian who coaxes Ellen De Generes out of the closet in the famous 1997 "The Puppy Episode" of the television series Ellen.On the April 24, 2007, airing of De Generes's talk show, Dern revealed she did not work for more than a year following her appearance in that episode because of resulting backlash, but nevertheless called it an "extraordinary experience and opportunity." Dern has been acknowledged with several awards from the independent film industry including the Sundance Institute and was the subject of an aggressive media campaign by David Lynch to win her an Academy Award nomination for her work in Inland Empire.She also starred as Ruth in the 1996 film Citizen Ruth, the directorial debut of Alexander Payne.Dern's mother makes a cameo appearance, playing Dern's character's mother, with Dern's character screaming a torrent of abuse at her.