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Linda
C. Samuelson, Ph.D.
~Professor of Molecular & Integrative Physiology
B.S. Michigan State
Ph.D., University of Chicago, 1984
2041 BSRB
(734) 764-9448
lcsam@umich.edu
Course
Director
Physiology
555, Integrative Genomics |
Current Research:
Dr. Samuelson’s research program is focused on the development and function of the gastrointestinal (GI) system, with particular focus on GI peptide hormones. The GI system produces an extensive array of hormones that serve to regulate digestion and metabolism. The cholecystokinin (CCK) family, which includes CCK, gastrin, and their two receptors, has been a long-term focus of the laboratory. Gene targeting was used to generate gastrin-deficient and CCK-deficient mice to examine the essential functions of these two hormones. The gastrin-deficient mice have impairment in the final differentiation or maturation of several cell types in the stomach, which leads to a severe loss of stomach acid secretion. Current experiments are focused on understanding the molecular mechanisms of gastrin-induced maturation of the stomach, and the importance of gastrin and histamine for the acid-secreting parietal cell. In addition we have recently generated a new transgenic mouse model that spontaneously develops autoimmune gastritis. We are studying the mechanism of autoimmunity and how inflammation leads to cellular transformation in the stomach.
CCK is expressed in a subset of endocrine cells in the intestine. We are studying the regulation of CCK gene expression to understand the mechanisms of development of intestinal endocrine cells. We have examined the timing of CCK gene expression in the developing intestine by generating a knock-in mouse strain in which the CCK gene was replaced by a lacZ reporter cassette. Our data show that CCK-expressing endocrine cells arise very early in intestinal development. Transgenic mouse experiments are ongoing to define the CCK gene sequences that are necessary for correct cell and developmental gene expression. We are testing the importance of basic helix loop helix transcription factors regulated by Notch signaling for development of intestinal endocrine cells. Future projects will describe the transcription factors required for intestinal endocrine cell gene expression, and to evaluate the lineage relationships between CCK-expressing endocrine cells and other endocrine cell populations in the small intestine.
Representative
Publications:
Samuelson, L.C., and K.L. Hinkle. Insights into the Regulation of Gastric Acid Secretion Through Analysis of Genetically Engineered Mice. Annu. Rev. Physiol. 65:383-400 (2003).
Hinkle, K.L., G.C. Bane, A. Jazayeri, and L.C. Samuelson. Enhanced Calcium Signaling and Acid Secretion in Parietal Cells Isolated from Gastrin-Deficient Mice. Am. J. Physiol 284:G145-G153 (2003).
Zavros, Y., K. Eaton, W. Kang, S. Rathinavelu, V. Katukuri, J.Y. Kao, L.C. Samuelson, and J.L. Merchant. Chronic Gastritis in the Hypochlorhydric Gastrin-Deficient Mouse Progresses to Adenocarcinoma. Oncogene 24:2354-2366 (2005).
Lay, J.M., G. Bane, C.S. Brunkan, J. Davis, L. Lopez-Diaz, and L.C. Samuelson. Enteroendocrine Cell-Expression of a Cholecystokinin Gene Construct in Transgenic Mice and Cultured Cells. Amer. J. Physiol. Gastrointest. Liver Physiol 288:G354-G361(2005).
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