Abstract

Intestinal epithelial growth regulation has become an area of intense research interest. Part of the reason for this interest stems from the notion that a basic understanding of this process may have a tremendous impact on our ability to understand diseases such as cancer and inflammatory conditions which affect the digestive tract. In the intestine, cell division is confined to epithelial cells located near the base of the crypt. As cells migrate from the crypt, cell proliferation ceases and they differentiate into enterocytes which have to process and absorb nutrients from the gut lumen. The investigator has cloned a new gene (GKLF) which appears to be associated with the growth arrest phenotype.
Three specific aims are proposed: a) examination of the structural-functional relationship of GKLF; b) determination of the effect of GKLF on cell growth; and c) analysis of the developmental expression pattern of GKLF in mice.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK052230-04
Application #
6177872
Study Section
Special Emphasis Panel (ZRG2-NTN (01))
Program Officer
May, Michael K
Project Start
1997-07-01
Project End
2001-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
4
Fiscal Year
2000
Total Cost
$246,553
Indirect Cost

  Institution

Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218

  Publications

He, Ping; Yang, Jong Won; Yang, Vincent W et al. (2018) Krüppel-like Factor 5, Increased in Pancreatic Ductal Adenocarcinoma, Promotes Proliferation, Acinar-to-Ductal Metaplasia, Pancreatic Intraepithelial Neoplasia, and Tumor Growth in Mice. Gastroenterology 154:1494-1508.e13
Nandan, Mandayam O; Bialkowska, Agnieszka B; Yang, Vincent W (2018) KLF5 mediates the hyper-proliferative phenotype of the intestinal epithelium in mice with intestine-specific endogenous K-RasG12D expression. Am J Cancer Res 8:723-731
Ghaleb, Amr M; Yang, Vincent W (2017) Krüppel-like factor 4 (KLF4): What we currently know. Gene 611:27-37
Kim, Chang-Kyung; He, Ping; Bialkowska, Agnieszka B et al. (2017) SP and KLF Transcription Factors in Digestive Physiology and Diseases. Gastroenterology 152:1845-1875
Kim, Chang-Kyung; Bialkowska, Agnieszka B; Yang, Vincent W (2016) Intestinal stem cell resurgence by enterocyte precursors. Stem Cell Investig 3:49
Snider, Ashley J; Bialkowska, Agnieszka B; Ghaleb, Amr M et al. (2016) Murine Model for Colitis-Associated Cancer of the Colon. Methods Mol Biol 1438:245-54
Ruiz de Sabando, Ainara; Wang, Chao; He, Yuanjun et al. (2016) ML264, A Novel Small-Molecule Compound That Potently Inhibits Growth of Colorectal Cancer. Mol Cancer Ther 15:72-83
Ghaleb, Amr M; Elkarim, Enas A; Bialkowska, Agnieszka B et al. (2016) KLF4 Suppresses Tumor Formation in Genetic and Pharmacological Mouse Models of Colonic Tumorigenesis. Mol Cancer Res 14:385-96
Bialkowska, Agnieszka B; Ghaleb, Amr M; Nandan, Mandayam O et al. (2016) Improved Swiss-rolling Technique for Intestinal Tissue Preparation for Immunohistochemical and Immunofluorescent Analyses. J Vis Exp :
Kuruvilla, Jes G; Kim, Chang-Kyung; Ghaleb, Amr M et al. (2016) Krüppel-like Factor 4 Modulates Development of BMI1(+) Intestinal Stem Cell-Derived Lineage Following ?-Radiation-Induced Gut Injury in Mice. Stem Cell Reports 6:815-824

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