"Scientist and M.D. come together." That's how Katherine Chetta, M.D., described, in a nutshell, the project that she and Mindy Engevik, Ph.D., have come together to tackle. Engevik's description was a bit more specific.
"The best research team of all time!"
Chetta is a neonatologist at the Medical University of South Carolina Shawn Jenkins Children's Hospital in the neonatal intensive care unit, specializing in the nutrition of the preterm infant. Engevik, an assistant professor in the MUSC College of Medicine in the Department of Regenerative Medicine and Cell Biology, runs a lab focused on gut microbiota. Together, Chetta said, they make up a powerful combination. "I feel like we're like an M.D.-Ph.D., but we're two people," she elaborated, half-jokingly. "I'm a full-fledged M.D. that has a lot of research interests, but she has the background to do these experiments."
The pair is currently taking on necrotizing enterocolitis. It's a big problem in the NICU, Chetta said, especially in preterm infants whose gastrointestinal systems can't determine whether bacteria is good or bad. The disease inflames and eventually kills tissue in the intestines, forcing the young patient to undergo surgery and antibiotics. She explained that necrotizing enterocolitis is fatal in about 50% of patients. "Infants can get colonized with really bad bacteria just from being in the hospital," Chetta said. "We really don't know why they can't modulate their own bacteria, like in adults and kids' guts, and respond to these bacteria but don't have the ability to allow good bacteria and not allow the bad."
Chetta decided to take this quandary to Engevik, who she met through a mutual colleague. The two found that they had a lot in common. For one, they both studied at Baylor College of Medicine in Houston but didn't know of each other. Engevik remarked that the two were like the proverbial "ships passing in the night." More importantly now, though, the two found a mutual interest in bacteria in the human gut and a mutual lack of concern for their own egos.
It turned out that Engevik's lab was the perfect place for Chetta to seek answers. She brought infant stool, breast milk and formula from SJCH along with tissue samples from a partnership with the Hollings Cancer Center Biobank.
"You can grow their intestine [from the tissue] as little organs called organoids," Engevik explained. "So we have these little infant organoids, and the thought is that we can then test out how these bacteria, after responding to nutrients that modulate the gut bacteria, and then, do preterm infants behave differently than term infants? Are their guts more mature?"
"There's so much we don't know about preterm infants," Chetta said. "That's why work of this nature is so important. Studies on the gastrointestinal systems of these vulnerable babies is kind of novel. Not a lot of people are doing the kind of work we do."
While it's still early in the research, the questions they are asking are already bearing fruit. Chetta said that the research has already allowed her to eliminate possible causes and focus more fully on more promising theories. "For example, we saw that introducing extra sodium didn't cause a reaction. Now I can stop worrying about salt with my patients," she said.
"Eventually," Engevik said, "we want to set up a clinical trial and send it to the NIH for funding, which would allow us to sign patients up."
In doing this kind of innovative work, there's always a temptation to use the project and its success to grow your own legacy. But when doctors collaborate like this, legacy building goes out the window.
"We're not the first people who have ever done this," Chetta said about their collaboration. "But a lot of successful collaborations are from someone who is a clinician and someone who is a Ph.D. that have come together and decided to answer a problem together. But one of the barriers to people working together is that they want it to be their project. Working together can bring a ton of success, but it makes you humble."
Though, as a researcher, she works on the academic side of MUSC, Engevik said she wants to help real people instead of just publishing papers.
"I can do as much microbiology as I want, but if I don't have any clinical applications, what really does it do for the world? I don't really need more papers. I'd rather get better treatments for patients."
Engevik is also quick to point out that this project has the potential to help more than just NICU patients. She said that necrotizing enterocolitis is similar to an adult condition like inflammatory bowel disease, which also currently has no cure.
"I think all of us have experienced or know someone with gut issues," Engevik said. "I think that these are really valuable questions, and I think if we can help people overcome these really bad GI issues, that we'll be better as a society," she added, referring to gastrointestinal conditions.
And for Chetta, she said that her venture into academic research is good for both her patients and her own mental health. She said that seeing the potential for cures in the lab helps her to keep going when she feels burnt out working in the NICU.
"At the end of the day, I'm doing the same thing over and over," Chetta said. "Then I want to come [to the lab] and do something long term and bigger than just the day to day. So it's a good balance – to get out and do some research on this. It gives me hope."
Chetta's work is funded by the Laura and David Stone Foundation, for neonatal research. Their joint work is supported by the MUSC Digestive Disease Research Core Center and COBRE in Digestive Liver Disease (P30DK123704).
