Dr. Juanita Merchant is a world-renowned molecular gastroenterologist whose contributions to the understanding of chronic inflammation and its association with gastric cancer have dramatically changed the way we look at these issues. She is widely known for her work on transcriptional control of gastrointestinal peptides, with a particular emphasis on the role of Hedgehog signaling in gastric transformation and how the gut microenvironment, or microbiome, regulates enteric glial cells and cellular senescence with aging.
Early on in her career, she received the 1998 American Gastroenterological Association (AGA) R. Robert & Sally D. Funderburg Research Award in Gastric Cancer from the AGA Research Foundation that allowed her to focus her investigations on how this important signaling pathway affects chronic inflammation that can drive cancer cell growth in the upper GI tract. Her research’s resulting findings changed physicians’ approach to diagnosis and treatment.
She has since been funded for more than two decades by the National Institutes of Health. She is an elected member of the National Academy of Medicine and an appointed member of the Board of Scientific Counselors for the National Institute of Diabetes and Digestive and Kidney Diseases, a unit of the NIH.
Among her most recent studies are the following:
- Study the role of environmental factors such as heavy metals on Helicobacter pylori infection and pre-cancer
In addition to the administration of survey instruments, endoscopic biopsies and urine will be collected from Native Americans undergoing procedures for dyspepsia to assess the efficacy of microRNA biomarker in predicting intestinal metaplasia and eventually gastric cancer.
- Sonic Hedgehog and Gastric Cancer
Studies from my lab focus on the role of bacterial colonization and the development of type B chronic atrophic gastritis in a mouse model. We found that the gastrin- deficient mice, which are hypochlorhydric, develop antral gastric tumors within 9-12 months of age. The tumpors appear to be dependent on the microflora. Gastric atrophy exemplified by loss of the acid- secreting parietal cell precedes tumor development as observed in human subjects. We found that Helicobacter infection coincides with acute secretion of Shh from the parietal cells then eventually reduced Shh expression prior to parietal cell atrophy. During infection by Helicobacter, Gli1+ immune cells are recruited to the stomach and over time change their phenotype from pro- inflammatory to immune- suppressive by becoming myeloid derived suppressor cells (MDSCs).
- Regulation of GI Growth and colon cancer by ZBP-89
We are also actively investigating the role of a zinc-finger transcription factors in the regulation of cell growth.
- Mechanism of Gastrinoma Development
We have developed a mouse model of gastrinoma — a tumor in the pancreas or duodenum that secretes excess of gastrin leading to ulceration in the duodenum, stomach and the small intestine — by crossing the villin- Cre mouse to the floxed menin mouse. Gastrinomas are the most malignant tumor that develops as a result of menin deletion. Menin is the protein product of the MEN 1 (multiple endocrine neoplasia) locus. Human subjects with MEN1 locus mutations develop tumors in neuroendocrine cells of the duodenum that secrete gastrin. We have found that mice conditionally heterozygous for the menin allele develop hypergastrinemia and G cell hyperplasia but not gastrinomas (tumors). We are now able to generate type 2 gastric carcinoids when MEN1 is deleted and placed on Sst-/- genetic background. The development of ECL cell hyperplasia is accelerated in the presence of acid suppression with a proton pump inhibitor (Sundaresan S., Gut, 2016). Moreover, gastrin- expressing cells appear in the lamina propria of the duodenum, which we hypothesize are the precursors of duodenal gastrinomas. Suprisingly, these gastrin+ cekks are enteric glial cells suggesting that they express gastrin under conditions that decrease the nuclear expression of menin through a PKA- dependent pathway (Sundaresan, S., Gastroenterology, 2017).
“Community to Get Glimpse into Future of Health Care in New Health Sciences Innovation Building” | Posted Oct. 31, 2019
“UA Gastroenterology, Cancer Center Partner to Put ‘Spotlight on Stomach Cancer’” | Posted Sept. 18, 2019
“‘Cookin’ Docs’ Video Series Launched by GI Division for Patient Dietary Needs” | Posted April 26, 2019
“Full House Hears UA Great Debate, ‘Prevention vs. Intervention,’ at Centennial Hall” | Posted April 23, 2019
“UA Gastroenterology Chief Dr. Juanita Merchant Elected to National Academy of Medicine Governing Council” | Posted Dec. 18, 2018
“Drs. Breathett, Merchant Spotlight DOM Research at 2nd Innovations & Inventions Fair” | Posted Oct. 18, 2018