Although she was born in Baton Rouge, Louisiana, young Denise was brought up in a clutch of Mississippi towns, including Pearl; Jackson; Madison, where she was a student at St. Joseph Catholic School; and Bay St. Louis, where she attended Our Lady Academy.
While growing up, her maternal grandmother, Grace Britton Sweet, has also held sway in Powell's life.
"My grandmother was a school teacher in Jackson. To this day, when I take her grocery shopping, her students come up and say how much of an impact she made on their lives," Powell said. "That's the kind of difference I want to make in my community."
"My mother is similarly there in such a defining way for her patients. She has worked with so many different communities, from Native American reservations to rural Mississippians to really sporty people in Colorado to male inmates to female veterans."
Still, Sweet may have thought her daughter was more likely to play a doctor on TV than be one.
"It really surprised me when she said she wanted to become a physician," Sweet said. "She was so interested in acting and modeling. I thought she would be in the entertainment business."
But along came the spiders. And then the children.
As a biology major enrolled at Loyola University New Orleans, Powell scrutinized arachnids in Belize before "accidentally falling in love with medicine." That happened during a stint at a charter school in New Orleans, working with academically, or behaviorally, compromised students.
"Instead of feeling challenged and defeated, I looked forward to seeing my students every week," she said. "And I knew pediatrics and adolescent medicine were for me."
Still, her mother had good reason to believe her daughter was a born entertainer. A veteran of local and school theater productions, Powell at one time also hopped back and forth between Jackson and Gulfport to play viola with two youth symphony orchestras on weekends, while running track and cross-country during the week. She also played basketball and joined a school swim team.
And, while she hasn't been a face on national TV, she has worked for mass media for about a year, writing online about health matters such as childhood trauma, the opioid epidemic and coping with tax season stress.
"Honestly, I just reached out to the ABC News producer, introduced myself and sent over my writing material from college and medical school – for the American Academy of Pediatrics, (the UMMC student newspaper) The Murmur, pieces like that," Powell said.
An ABC News producer bit.
"Then, I was off to the Big Apple to write and help out with 'Good Morning America,' '20/20,' 'World News Tonight' and ABC News." Powell said. "My favorite moment was walking into a meeting and seeing (news anchor) David Muir just chilling at the end of the table to hear our pitches.
"I love being in a room of people who know more than me, because it allows me to learn. Working in these spaces, everyone knows something different and has a different degree or background, and that has helped me grow a lot."
On the set of "Good Morning America," she met her favorite actor, Dwayne "The Rock" Johnson.
"He asked me where I'm from, to which I replied, 'Mississippi,'" Powell said. "He then said with a chuckle, 'You don't sound like you're from Mississippi.'
"I don't get nervous easily, but I nearly fainted right then and there."
The reporting and writing experience for her was also heady, said Powell, who landed a similar job with the CNN News Health Unit. To her surprise, reporting roused her interest in politics.