Yeardley Smith knew early on that her distinctive voice—some might say “high pitched”—could stand in her way as an actor of stage and screen. Although she got this reminder all too often throughout her formative years, she stayed her course.

“Who cares what the naysayers think,” says Smith, the French-born, Emmy-winning actor best known as the voice of Lisa Simpson from the long-running animated show, The Simpsons. “They don’t know you in the way that you know yourself. Take every opportunity, because you don’t know where it’s going to lead and how it’s going to connect with the next one. … If you had said to me at the start of my acting career that my greatest success is going to come from voiceover work, I would have doubted it. But without question, Lisa Simpson is one of the greatest gifts in my life.”

In addition, Smith has become known for her comedic timing on TV’s Herman’s Head and Dharma & Greg, as well as in films such as City Slickers and As Good as It Gets. She has also found richness in her true-crime podcast Small Town Dicks, a quirky YouTube cooking show called Oil & Water, and her new production company, Paperclip LTD.

We spoke with the 57-year-old actor about what she has learned from Lisa Simpson, her fascination with true crime and her best advice.