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She went on to study journalism as an undergraduate, first at the University of Connecticut and then at New York University.During college, she acted in television commercials and the soap opera "As the World Turns" to earn extra money.Due to her success as an actress, she dropped out of college a semester before she would have graduated.After her film debut in George Cukor's Rich and Famous, Ryan played Betsy Stewart in the daytime drama As the World Turns, from 1982 to 1984, and her character was featured in a popular romantic story arc.Around that same time, she appeared in a Burger King commercial.Several television film and smaller film roles followed, including Charles in Charge, Armed and Dangerous, Amityville 3-D and Promised Land; for her role in the latter she received her first Independent Spirit Award nomination. She also previously made an appearance in interstellar.They had previously been paired as romantic leads in the film Joe Versus the Volcano—which was a commercial disappointment, but later developed a cult following—and they would later be paired for a third time in the film You've Got Mail.
After early roles in films such as Top Gun (1986), Innerspace (1987), and Promised Land (1987), she achieved international recognition for her lead performance in When Harry Met Sally...
(1989), which earned her her first Golden Globe nomination.
In 1986, she played Carole Bradshaw, the wife of Naval Flight Officer Nick "Goose" Bradshaw (played by Anthony Edwards) in Top Gun. Her first leading role was the romantic comedy film When Harry Met Sally...
Ryan starred in the film Innerspace with her future husband Dennis Quaid, then in the remake of D. (1989), which paired her with comedic leading man Billy Crystal and earned her a Golden Globe nomination.
Ryan subsequently established herself as one of the most successful actresses of the 1990s, particularly in romantic comedy films, such as Joe Versus The Volcano (1990), Sleepless in Seattle (1993), French Kiss (1995), You've Got Mail (1998), and Kate & Leopold (2001). She has two sisters, Dana and Annie, and a brother, musician Andrew Hyra, a member of the band Billy Pilgrim.
Her other films include The Doors (1991), When a Man Loves a Woman (1994), Courage Under Fire (1996), City of Angels (1998) and Proof of Life (2000). Her parents divorced in 1976, when she was 15 years old.