The long-term goal of the proposal is to define the cellular processes that regulate proliferation, differentiation, and gene expression in the intestine. The fundamental premise is that cyclin-dependent kinase inhibitors are activated when intestinal stem cells become activated crypt cells. One such cyclin-dependent kinase inhibitor is p27 which may act independently from G1 cyclins and cdks. In addition, multiple redundant genes control proliferation and differentiation, apart from p27. Therefore, the proposed studies will focus upon inhibiting p27 to assess effects upon differentiation; to elucidate the role of Jab 1 in the regulation of p27 expression; to correlate differentiation-inducing properties of p27 with a subdomain of the protein; to identify p27 interacting proteins and to determine their expression in vitro and in vivo; and to continue identification of novel genes that regulate intestinal differentiation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK048331-04
Application #
6194008
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
May, Michael K
Project Start
1996-09-01
Project End
2005-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
4
Fiscal Year
2000
Total Cost
$246,993
Indirect Cost
Name
Cornell University
Department
Other Basic Sciences
Type
Schools of Veterinary Medicine
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Sorensen, Mathew D; Harper, Jonathan D; Hsi, Ryan S et al. (2013) B-mode ultrasound versus color Doppler twinkling artifact in detecting kidney stones. J Endourol 27:149-53
Sorensen, Mathew D; Bailey, Michael R; Shah, Anup R et al. (2012) Quantitative assessment of shockwave lithotripsy accuracy and the effect of respiratory motion. J Endourol 26:1070-4
Shah, Anup; Harper, Jonathan D; Cunitz, Bryan W et al. (2012) Focused ultrasound to expel calculi from the kidney. J Urol 187:739-43
Rimondi, Erika; Secchiero, Paola; Quaroni, Andrea et al. (2006) Involvement of TRAIL/TRAIL-receptors in human intestinal cell differentiation. J Cell Physiol 206:647-54
Weng, Xing-He; Beyenbach, Klaus W; Quaroni, Andrea (2005) Cultured monolayers of the dog jejunum with the structural and functional properties resembling the normal epithelium. Am J Physiol Gastrointest Liver Physiol 288:G705-17
Quaroni, A; Tian, J Q; Seth, P et al. (2000) p27(Kip1) is an inducer of intestinal epithelial cell differentiation. Am J Physiol Cell Physiol 279:C1045-57
Quaroni, A; Tian, J Q; Goke, M et al. (1999) Glucocorticoids have pleiotropic effects on small intestinal crypt cells. Am J Physiol 277:G1027-40
Tian, J Q; Quaroni, A (1999) Involvement of p21(WAF1/Cip1) and p27(Kip1) in intestinal epithelial cell differentiation. Am J Physiol 276:C1245-58
Tian, J Q; Quaroni, A (1999) Dissociation between growth arrest and differentiation in Caco-2 subclone expressing high levels of sucrase. Am J Physiol 276:G1094-104
Quaroni, A; Paul, E C (1999) Cytocentrin is a Ral-binding protein involved in the assembly and function of the mitotic apparatus. J Cell Sci 112 ( Pt 5):707-18

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