After leaving the University of South Florida, she relocated to New York City, where she became a street musician for many years.

Beginning in mid-1980s Tyrell worked with David Johansen and his Buster Poindexter alter-ego for fifteen years, appearing on six albums and a number of tours as well as collaborating on the musical Poet's Café.

Tyrell, Scialfa and Lowell performed on David Johansen's stage named eponymous first Buster Poindexter album released in 1987 on RCA Records featuring the popular dance hall single, "Hot-Hot-Hot"; their friendship and mutual recording industry projects continue to the present.

She contributed to Springsteen's albums Magic (2007), Working on a Dream (2009), Wrecking Ball (2012), High Hopes (2014), Western Stars (2019) and Only the Strong Survive (2022) and the subsequent Springsteen and the E Street Band's Magic, Working on a Dream, and Wrecking Ball Tours, where she was onstage for every number, playing acoustic guitar in addition to violin, and singing some featured duet parts during absences of bandmate and Springsteen's wife Patti Scialfa.

On the album she performed "Danger Zone" - a Percy Mayfield song made famous by Ray Charles.