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Lopes was born in Philadelphia, Pennsylvania, the daughter of Wanda Denise (nee Andino), a seamstress, and Ronald Lopes Sr., a US Army staff sergeant, of Portuguese background. She had a younger brother, Ronald Jr., and a younger sister, Raina Anitra (who professionally goes by Reigndrop). Lopes said her father was "very strict, very domineering" and that he treated the family like they were in "boot camp". He was a "talented musician" and played the harmonica, clarinet, piano, and saxophone.

In 1998, Lopes hosted the short-lived MTV series, The Cut, in which a handful of aspiring pop stars, rappers, and rock bands competed against each other in front of judges. The show's winner, which ended up being a male-female rap duo named Silky, was promised a record deal and funding to produce a music video, which would then enter MTV's heavy rotation. A then-unknown Anastacia finished in third place, but ended up securing a record deal after Lopes and the show's three judges were impressed by her performance.  After the release of FanMail, Lopes began to expand her solo career. She became a featured rapper on several singles, including Spice Girl Melanie C's "Never Be the Same Again", which topped the charts in 35 countries, including the United Kingdom. She was also featured on "U Know What's Up", the first single from Donell Jones' second album, Where I Wanna Be, and she rapped a verse in "Space Cowboy" with NSYNC on their 2000 album, No Strings Attached. On October 4, 2000, Lopes co-hosted the UK's MOBO Awards with Trevor Nelson, where she also performed "U Know What's Up" with Jones. She also collaborated on "Gimme Some" by Toni Braxton for her 2000 album The Heat. She had previously featured on Keith Sweat's song "How Do You Like It". In 2001, she appeared in a commercial for Gap. In July 2001, Lopes appeared on the singers' edition of Who Wants to Be a Millionaire along with Joey McIntyre, Tyrese, Nick Lachey, and Lee Ann Womack. She dropped the $125,000 question and won $32,000 for her charity. After her death in 2002, the episode she appeared in was shown and was dedicated to her.  Lopes created "Left Eye Productions" to discover new talent. She mentored the R&B trio Blaque, and helped them secure a record deal with Columbia Records. Their self-titled debut album was executive-produced by Lopes, who also made a cameo appearance in their music video "808" and also rapped in their second music video "I Do". Lopes was also developing and promoting another new band called Egypt. They worked with Lopes on her second album under her new nickname, N.I.N.A., meaning New Identity Not Applicable.  In 1996, Lopes created the UNI Studios for the purpose of recording solo projects. Lopes' family opened the studio to the public. Her brother Ronald is the general manager of the studio. Lopes had a dream of making new artists able to record music at a low cost, in a high-end studio at her house. Her family continues to operate it and fill it with new equipment.
Lisa Lopes