Digestive Disease Branch

Gastroenterology Section

Stephen A. Wank, M.D., Section Chief

The Gastroenterology Section performs research studies on the neuroendocrine hormonal regulation of digestion in healthy and disease states in both the laboratory and at the bedside through clinical research protocols.

In addition, the section (1) oversees the clinical and research training of second and third year fellows leading to Board Certification in Gastroenterology and (2) is responsible for the gastroenterology clinical consultation service for the NIH Clinical Research Center.

The major laboratory areas of interest are (1) gastrointestinal (GI) endocrine hormone/receptor molecular interaction and intracellular signaling; (2) the molecular basis for the chemosensation of ingested nutrients such as amino acids, glucose, calcium, hydrogen ions, and fatty acids by G protein-coupled receptors expressed on enteroendocrine cells resulting in hormone (e.g., gastrin and cholecystokinin) and acid secretion; and (3) development of the enteroendocrine cell lineage and fate using a variety of transgenic mice and cultured small intestinal organoids.

The major translational clinical research interests include: (1) discovery and clinical description of the natural history of a familial form of serotonin secreting neuroendocrine carcinoid tumors; (2) familial carcinoid tumor genetic linkage analysis and molecular genetics to identify causal mutations in affected families; (3) the carcinogenesis of small intestinal carcinoid tumors from crypt based enterochromaffin cells; (4) chemotherapy of type II gastric carcinoids using a gastrin receptor (CCK2R) antagonist, YF-476; and (5) development of a novel, non-invasive method of determining the level of gastric acid secretion necessary to monitor response to acid suppression therapy in the treatment of gastroesophageal reflux disease and acid hypersecretory states (e.g., Zollinger-Ellison syndrome).

Gastrointestinal Cell Biology Section

Robert T. Jensen, M.D., Section Chief

The Gastrointestinal Cell Biology Section conductions studies on the cellular basis of action of GI hormones, as well as clinical and laboratory studies on human gastric acid hypersecretory states (e.g., Zollinger-Ellison syndrome). In the area of GI hormones, research primarily focuses on bombesin-related peptides, the gastrin-releasing peptide, neuromedin B, CCK-related peptides, and VIP-secretin related peptides. These studies examine intracellular signaling cascades, especially tyrosine phosphorylation (primarily CCK, Bombesin), and the molecular pharmacology of their receptors (especially Bombesin related peptides). The Section also conducts structure-function studies of various receptor ligands, with the aim of developing selective agonists and antagonists. Laboratory studies characterize the bombesin-related receptor, BRS-3, and develop ligands to deliver receptor-specific chemotherapy to tumors ectopically expressing these receptors. Clinical studies of Zollinger-Ellison syndrome include the diagnosis, localization, and treatment of the gastrinoma, as well as multiple endocrine neoplasia type 1, which occurs in a proportion of these patients. Accompanying laboratory studies characterize the molecular pathogenesis of gastrinomas and identify prognostic factors.

Molecular and Clinical Nutrition Section

Mark A. Levine, M.D., Section Chief

The Molecular and Clinical Nutrition Section determines optimal nutrition in health, disease, and disease treatment using vitamin C (ascorbic acid) as a model nutrient. Research examines how specific nutrient function occurs in relation to nutrient concentration, in vitro (in cells and organelles) and in vivo (animals and people). Work focuses on a functional basis for nutrient recommendations, rather than reliance on preventing deficiency, which agencies have used for many years. Many countries now base Recommended Dietary Allowances for vitamin C, in part, on this work.

Specific projects encompass basic, translational, and clinical research in the following areas: ascorbic acid function in relation to concentration in cells and subcellular organelles; ascorbic acid transport and accumulation mechanisms; ascorbic acid pharmacokinetics (dose concentration relationships) in animals and people; pharmacologic ascorbic acid as a pro-drug for hydrogen peroxide formation in vivo and for treatment of cancer and infectious diseases; ascorbic acid and free radical biology; and the regulation of glucose transport in vitro and in vivo.