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Vol. LX, No. 11
May 30, 2008

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Merchant To Give Wednesday Afternoon Lecture, June 11

  Molecular gastroenterologist Dr. Juanita L. Merchant will present the Wednesday Afternoon Lecture at 3 p.m. on June 11.  
  Molecular gastroenterologist Dr. Juanita L. Merchant will present the Wednesday Afternoon Lecture at 3 p.m. on June 11.  

NIDDK will host molecular gastroenterologist Dr. Juanita L. Merchant as she presents “The Role of Sonic Hedgehog in Gastric Homeostasis and Cancer” for the NIH Director’s Wednesday Afternoon Lecture at 3 p.m. June 11 in Masur Auditorium, Bldg. 10. A brief reception will follow.

Chronic inflammation in the stomach (gastritis) induces gastric atrophy characterized by the loss of the acid-secreting oxyntic glands. Studies in humans and in Mongolian gerbils have shown that chronic inflammation from H. pylori begins in the antrum and triggers pyloric gland and intestinal metaplasia that subsequently spread to the corpus. Gastric cancers arise from a mucosal background of metaplasia. Although H. pylori infection is the major reason chronic inflammation develops in the stomach, the molecular networks linking chronic inflammation to the atrophic/metaplastic changes are not well understood.

However, modulations of the cellular line-ages that emerge during gastritis are reminiscent of perturbed developmental pathways. Indeed, studies have found that gastric “metaplasia” develops in the sonic hedgehog (Shh) null mouse, suggesting that loss of this peptide morphogen might contribute to gastric atrophy. Shh is not only essential for gastrointestinal tract development but also for maintaining normal acid-secretion in the adult stomach. Gastrin is the only hormone capable of stimulating gastric acid and is thus required to maintain functional parietal cells.

Merchant has shown that gastrin null mice have gastric atrophy and metaplasia before distal, intestinal-type gastric cancer develops. Since reduced levels of Shh peptide correlate with gastric atrophy, her lab examined whether gastrin regulates Shh expression in parietal cells and found that processing of Shh in the normal stomach is hormonally regulated, acid-dependent and mediated by the aspartic protease pepsin A. Moreover parietal cell atrophy, a known pre-neoplastic lesion, correlates with loss of Shh processing.

Known internationally for studies of transcriptional control mechanisms in the gastrointestinal tract, Merchant has made paradigm-shifting contributions to understanding chronic inflammation in the stomach. Her lab has shown that inflammatory mediators, particularly the proinflammatory cytokine interferon gamma, induce expression of the gastric hormone gastrin. She hypothesized that the acid regulatory peptides gastrin and somatostatin are targets of the innate immune system and has reevaluated Helicobacter pathogenesis and the control of acid secretion in the context of gastric inflammation. Merchant is now applying new knowledge of gastric inflammation to understanding parietal cell atrophy and preneoplastic changes in the stomach.

Merchant is professor of internal medicine and of molecular and integrative physiology at the University of Michigan. She earned both medical and doctoral degrees from Yale University and completed residency and fellowship training at Massachusetts General Hospital. She is a member of NIDDK’s National Advisory Council and the NIH Council of Councils and is active in NIDDK’s Network of Minority Research Investigators, which encourages underrepresented racial and ethnic minorities to conduct biomedical research. NIH Icon

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