Medical Student Perseveres all the way to Guatemala Capstone Research

Amanda-Lynn Marshall is the picture of determination. She demonstrated so as an advocate for children with craniofacial anomalies even before arriving at Oakland University William Beaumont School of Medicine (OUWB). She showed it in her Capstone Project topic, which sought to investigate why children in remote Guatemala faced similar adversities. But she likely validated it the most when it came to her recovery from a devastating automobile accident that happened shortly before she was slated to go to Guatemala and left her seriously injured and facing multiple surgeries. A year later, Marshall is now getting back on track.

When she started as a medical student, Marshall met Beaumont pediatrician and faculty member Jay Eastman, M.D., through a mutual interest in global health and a shared connection with Rotary International. Marshall had already earned an MPH in environmental health and toxicology as a Rotary Ambassadorial Scholar in Grenada where she focused on craniofacial anomalies. As director of Casa Colibri, a nonprofit humanitarian organization dedicated to helping the Mayan people of Guatemala, Eastman presented Marshall with a case series regarding a specific neural tube defect prevalent to children born in a remote region of Guatemala.

“Over several years, a series of patients with the anterior encephalocele, frontoethmoidal encephalocele, presented to his clinic in Guatemala,” explains Marshall. “I was immediately intrigued by the cohort of children. Armed with my background in environmental and public health I started digging and came across the research of a scientist, Dr. Ron Riley, who suspected mycotoxins as a risk factor for neural tube defects. Once I got my hands on that, I kind of took off with it, probably much to Dr. Eastman’s surprise.”

A Capstone Research First

From there it unfolded and soon Marshall was set to embark on OUWB’s first international Capstone Project. But the accident put everything on hold until she was no longer wheelchair-bound and was well enough to continue. Though still in a hip brace, Marshall made that trip in April to examine fumonisin (toxins caused by fungus found in corn and corn products) exposure in Guatemalan women of childbearing age. First, she conducted a case study of the various encephalocele cases, identifying villages afflicted with frontoethmoidal encephalocele. From there she designed an investigation to ascertain fumonisin exposure in and around afflicted villages by collecting both urine and blood specimens.

Frontoethmoidal encephaloceles are an anomaly in which the brain and surrounding meninges herniate through the anterior skull defect. Marshall hypothesized that the Mayan’s diet being centralized around maize, likely had high exposures to the mycotoxin fumonisin.

“Through her research she learned there was a mold in their corn that others have linked to these defects,” explains Judith Venuti, Ph.D., Professor and Chair of Biomedical Sciences and Marshall’s Capstone mentor. Venuti joined Marshall and Eastman on the trip and describes Marshall as the driving force of the project. “She is very resourceful.”

Marshall contacted Dr. Ronald Riley, research toxicologist and lead scientist with the USDA’s Toxicology and Mycotoxin Research Unit and adjunct faculty at University of Georgia, to express her interest in conducting fumonisin research in an isolated region in the highlands of northwestern Guatemala. He offered to do the analyses free of charge and to mentor Marshall in the aspect of toxicology and fumonisins. He also introduced her to a scientist in Guatemala, Dr. Olga Torres, who would conduct the initial sample processing in Guatemala City.

“Dr. Riley has measured this in the corn before, but not in this area of Guatemala, because it’s so remote. So Amanda-Lynn thought we should look at this region. She questioned the villagers about how they process their corn,” explains Venuti.

Interviews Lead to Important Discovery

Marshall interviewed villagers to learn more about the drying process and found that in some cases it was in close proximity to chemicals.

“Some of the villagers were storing aluminum phosphide, which gives off phosphine (a known teratogen), with their dried corn. That also is a very plausible piece of the puzzle,” says Marshall. “With each village I was able to do a survey of how they acquired the corn, the process for drying and storage, and to take note of each of those individual practices.”

With regards to the cases of frontoethmoidal encephalocele she also researched the month of conception, the age of the mother, and other co-morbidities.

“Research has shown that children conceived during the rainy season have a higher risk of neural defects,” Marshall says. “This is where something like mycotoxins come into play, as exposure might be more prevalent in the rainy season than the dry season.”

Previous studies show that mice exposed to fumonisin can counteract the mycotoxin with various levels of prenatal vitamins -- B vitamins and folate in particular -- to reduce the risk back to what it was before the fumonisin exposure.

“This toxin inhibits the pathway through which folic acid works. Folic acid is known to be essential, particularly to people in childbearing years because one is susceptible to this before you know you’ve conceived. The events that lead to these defects occur very early in development,” says Venuti, an embryologist, adding that moldy corn is considered a delicacy in the region, further complicating the prevention.

Plus this mostly impoverished population consumes very little folate in general, says Marshall, describing their diet as rich in tortillas, with limited leafy green vegetables.

“Existing nutritional deficiencies, compounded with exposure to the mycotoxin fumonisin is very likely increasing the risk for this particular defect,” says Marshall.

Next Steps in the Research Process

For now, Marshall awaits the data so that she can begin to prioritize villages which have the highest exposure and work to determine how best to educate about and make available prenatal supplements, as well as best practices for processing and storing corn to minimize phosphine exposure, to work towards preventing neural tube defects.

For her dedication to the project, Eastman calls Marshall an amazing young woman.

“For her to conceive of and put together and be able to complete this study the way that she has done, particularly with what she has to face physically, is nothing short of miraculous,” explains Eastman. “Really this whole study was her design and she’s followed through on it and I think it’s just amazing for someone who’s a medical student to conceive of this and make it happen.”