Julie In, PhD, received a $1.9 million grant from the National Institute of Environmental Health Sciences to study the impact of uranium on the cells that line the intestines.
In, an associate professor at The University of New Mexico and a scientist at the UNM Comprehensive Cancer Center, will study the molecular changes that take place within these intestinal lining cells when they are exposed to uranium dust. The work could be applied to several gut diseases, including irritable bowel syndrome and colon cancer.
Uranium and other heavy metals, such as arsenic and vanadium, can get into groundwater and air from abandoned uranium mine sites. Of the more than 1,600 such sites scattered throughout the western United States, at least 500 lie within the Four Corners region.
Many tribal and rural communities in New Mexico are located near abandoned uranium mine sites, and dust containing uranium is ubiquitous in these communities. The dust can get into the lungs and also accumulate in the colons of the people living there.
“Approximately 60% of what we inhale we also ingest,” In says.
In will use colonic organoids, which are miniature models of a colon, to study how uranium affects the cells that line the colon. She grows the organoids from cells taken during routine diagnostic or screening colonoscopies or during endoscopies.
The organoids contain the different kinds of cells found in the lining of the colon — called the colon epithelium — and they produce mucus and hormones and otherwise behave as if they are within a living colon. They enable In to study changes in the colon epithelial cells when uranium dust settles on them.
Approximately 60% of what we inhale we also ingest.
One of the important changes that In observed in her preliminary studies was a decrease in the amount of mucus that the colon epithelium produced. The mucus protects the colon epithelial cells from the bacteria and digestive fluids in the colon.
In will use the grant to study the effects of a thinner mucus and how this thinning affects the colon epithelial cells. She’ll also study the molecular changes in goblet cells, which produce the mucus, when they are exposed to uranium dust.
The other important change In observed was in the balance of hormone-producing enteroendocrine cells.
“We don’t think of the gut as an endocrine organ,” she says, “but due to the presence of enteroendocrine cells and the cumulative amount [of hormones produced], the gut is actually the largest endocrine organ in our body.”
We don’t think of the gut as an endocrine organ, but due to the presence of enteroendocrine cells and the cumulative amount [of hormones produced], the gut is actually the largest endocrine organ in our body.
In’s preliminary studies found that some enteroendocrine cells increased in number, and this increase resulted in an imbalance of hormones. Using the organoids, In will closely measure the molecular changes that occur in the enteroendocrine cells after being exposed to uranium dust.
“Having this increase in these hormone-producing enteroendocrine cells with [this organoid] model using uranium-bearing dust could help us understand a whole cohort of other diseases and other therapeutics,” she says.
In explains that in many diseases of the colon, epithelial cells show the same responses early in the disease evolution. The molecular work she plans could therefore benefit research in colon cancer, irritable bowel syndrome and other colonic diseases and could lead to drugs that help fight all these diseases.
In is particularly interested in studying colon cancer. She says that while the total number of colon cancer cases has decreased in the United States, it has skyrocketed in younger people.
“I’m hoping,” In says, “that we can be one of many studies that helps to understand these early molecular changes that happen within our gut epithelia, that drives these diseases particularly among young people.”
About Julie In, PhD
Julie In, PhD is an assistant professor in the Department of Internal Medicine, Division of Gastroenterology and Hepatology at The University of New Mexico School of Medicine and a member of the UNM Comprehensive Cancer Center.
About the Grant
The National Institute of Environmental Health Sciences of the National Institutes of Health supported the research reported in this publication under Award Number 1R01ES034400-01A1, Heavy metals exposure regulates secretory lineage in intestinal injury, Principal Investigator: Julie Goeun In, PhD. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
UNM Comprehensive Cancer Center
The University of New Mexico Comprehensive Cancer Center is the Official Cancer Center of New Mexico and the only National Cancer Institute-designated Cancer Center in a 500-mile radius.
Its more than 136 board-certified oncology specialty physicians include cancer surgeons in every specialty (abdominal, thoracic, bone and soft tissue, neurosurgery, genitourinary, gynecology, and head and neck cancers), adult and pediatric hematologists/medical oncologists, gynecologic oncologists, and radiation oncologists. They, along with more than 600 other cancer healthcare professionals (nurses, pharmacists, nutritionists, navigators, psychologists and social workers), provide treatment to 65% of New Mexico’s cancer patients from all across the state and partner with community health systems statewide to provide cancer care closer to home. They treated almost 15,000 patients in more than 100,000 ambulatory clinic visits in addition to in-patient hospitalizations at UNM Hospital.
A total of nearly 1,855 patients participated in cancer clinical trials testing new cancer treatments that include tests of novel cancer prevention strategies and cancer genome sequencing.
The more than 123 cancer research scientists affiliated with the UNMCCC were awarded $38.2 million in federal and private grants and contracts for cancer research projects. Since 2015, they have published nearly 1000 manuscripts, and promoting economic development, they filed 136 new patents and launched 10 new biotechnology start-up companies.
Finally, the physicians, scientists and staff have provided education and training experiences to more than 500 high school, undergraduate, graduate, and postdoctoral fellowship students in cancer research and cancer health care delivery.