By 2009, she was living half-broke in New York City and studying at Queens College for her doctorate when she chanced to meet comic and political gadfly Bill Maher. During the romance that followed, she relocated to LA and made a Maher-produced pilot for HBO (a sort of template for, and not coincidentally bearing the same title as, “Talk Nerdy To Me”) that didn’t get picked up. Maher is pals with Arianna Huffington, though, who told Santa Maria that HuffPost would love to have her voice in its new science section.

Santa Maria’s early video efforts for HuffPost leaned heavily on matters of sex and mental health. She hesitated before opening up about her own struggle, since childhood, with depression so severe that (as she told an interviewer on the website The Mental Illness Happy Hour) there were times she had to “stare somebody you love in the face and say, ‘You can’t help me.’ ” Despite a warning from a mentor at AOL that, “Whatever you put out on the Internet will never go away,” Santa Maria ultimately decided to use her own story to inform her video reports on depression. In a December 2011 episode of “Talk Nerdy,” she says her depression wrecked relationships of all sorts: “I felt worthless, I felt guilty, I had no self-esteem. I couldn’t eat or sleep. If I started to cry, I couldn’t stop.”

Since going public, she has not been shy about asserting that her daily 20-milligram dose of Celexa is not only a key to productivity, but “to being good to the people I love.” She says that she was, and probably still is, difficult to be in a relationship with, “because I am a bundle of contradictions; I am simultaneously headstrong and determined and a total mess who needs a lot of attention and is kinda needy and insecure.”

For all the seeming self-absorption, Santa Maria is quick to laugh, a patient listener who seems eager to compliment her colleagues, and for part of an afternoon at least, a study in consideration. More than once, without a trace of sarcasm, she asks a member of her team, “Can you do me a big favor?” when the task really was part of the person’s daily routine.

The more she talks, the easier it is to understand her fastidious desire to reconcile the contradictions of her show—and of her role as a science teacher and budding Web personality. A question about the career advantages of her looks, then, leads to a discussion of who her audience is—mostly men, late teens to probably mid-40s—and how she would like it to be broader, more diverse, more female.

But it is also clear that she is beginning to understand the expectations—and limitations—that come with even a small dose of celebrity. “With the lip-ring thing,” she says, “lately I’ve been thinking, I’m almost 30—how old is too old to have the lip ring? Will people be saying, ‘Why does that old lady have a lip ring?’ Now I have to think not just for me, but for all these people who watch the show. Sometimes I want to cut off all my hair or dye it blue like I used to, but it’s, ‘Uhh . . . probably shouldn’t do that.’”

On the set, as Santa Maria rigs her own microphone into position and hand-coifs her long brown hair, she continues to worry over the script. “I hope this sounds pretty conversational,” she says. “I don’t know why this was such a bitch for me to write. I keep wanting to go off on a rant about tradition and religiosity.”

With the cameras rolling, she delivers the material smoothly. “Most of us have been to a funeral and we’ve seen a coffin get lowered into the ground,” she says, “but what’s happening inside that coffin, especially after weeks or months?” She and Sprinkle pause with unspoken assent when a truck rumbles by outside—the stage is an ad-hoc affair wherein a window that was sheet-rocked off still admits traffic noise—and Santa Maria picks the story back up once the truck has passed: “It’s pretty hard to become one with Mother Nature when there’s cement, wood, rubber, steel, and embalming fluid protecting you from the elements.”

Fred Schruers is a freelance writer based in Los Angeles.