James C. Fleet
B.S. Cornell University, 1981 M.S. University of Delaware, 1984 Ph.D. Cornell University, 1988
Chromatin and Regulation of Gene Expression
Molecular Signaling and Cancer Biology
Current Research Interests:
Vitamin D signaling mechanisms: 1,25 dihydroxy vitamin D (1,25 VD), is a ligand for the steroid hormone receptor family member, the vitamin D receptor (VDR). Activation of the VDR by its ligand stimulates gene transcription leading to the production of proteins that control whole body calcium and bone metabolism as well as the anticancer actions of 1,25 VD and 1,25 VD analogs. My group examines the factors that modulate the molecular actions of vitamin D. Recently we have been examining: how 1,25 D stimulates intracellular movement and DNA binding and the impact of activated kinase pathways on vitamin D metabolism and VDR function.
We also conduct translational research using genetically modified mice to determine whether the mechanisms we identify in cell models apply to complex physiological systems. This includes making tissue-specific transgenic mice to recover knock-out phenotypes and creating new animal disease models.
Wang, L., Klopot, A., Freund, J.N., Dowling, L.N., and Krasinski, S.D., and Fleet, J.C. (2004) Control of Differentiation-Induced Calbindin-D9k Gene Expression in Caco-2 Cells by Cdx-2 and HNF-1?. Am. J. Physiol. 287:G943-953.
Fleet, J.C. (2007) Using genomics to understand intestinal biology. J. Physiol. Biochem. 63:83-96.
Fleet, J.C. (2007) What have genomic and proteomic approaches told us about vitamin D and cancer? Nutr. Rev. 65:S127-130.
Klopot, A., Hance, K.W., Peleg, S., Barsony, J. and Fleet, J.C. (2007) Nucleo-cytoplasmic Cycling of the Vitamin D Receptor in the Enterocyte-like Cell Line, Caco-2. J. Cell. Biochem. 100:617-28.
Song, Y. and Fleet, J.C. (2007) 1,25 Dihydroxyvitamin D-Mediated Intestinal Calcium Absorption is Blunted in Mice Heterozygous for the VDR Knockout Allele. Endocrinology. 148:1396-402.
Marks, H.D., Fleet, J.C., Peleg, S. (2007) Transgenic expression of the human vitamin D receptor (hVDR) in duodenum of VDR-null mice attenuates age-dependent decline in calcium absorption. Proceedings of the 13th Workshop on Vitamin D. J. Steroid Biochem. Mol. Biol. 103:513-6.
Thalacker-Mercer, A.E., Fleet, J.C., Craig, B.A., Carnell, N.S., Campbell, W.W. (2007) Inadequate protein intake affects muscle gene expression in older humans. Am. J. Clin. Nutr. Am. J. Clin. Nutr. 85:1344-52.
Zhao, Y., Fleet, J.C. Adamec, J., Terry, D.E., Zhang, X., Davisson, V.J., Weaver, C.M. (2007) Effects of Hindlimb Unloading and Bisphosphonates on the Serum Proteome of Rats. Bone 41:646-658.
Rowling, M.J., Gliniak, C., Welsh, J., Fleet, J.C. (2007) High dietary vitamin D can recover the bone phenotype of CYP27B1 null mice. J. Nutr. 137:2608-2615.
Fleet, J.C., Gliniak, C., Zhang, Z., Xue, Y., Barzan, K., McCreedy, R., and Adedokun S.A. (2008) Serum metabolite profiles and target tissue gene expression define the impact of cholecalciferol intake on calcium metabolism in rats and mice. J. Nutr. 138:1114-1120.
Fleet, J.C. (2008) Molecular Actions of Vitamin D relevant to Cancer prevention. Molecular Aspects of Medicine 29(6):388-96.
Cui, M., Klopot, A., and Fleet, J.C., (2009) The impact of differentiation on 1,25 dihydroxyvitamin D-mediated gene expression in the enterocyte-like cell line, Caco-2. J. Cell Physiol. 218:113-21.
Cui, M., Zhao, Y., Hance, K.W., and Fleet, J.C. (2009) MAPK signaling enhances 1,25 dihydroxyvitamin D-mediated CYP24 gene expression in the enterocyte-like cell line, Caco-2. A differential role for Ets1 phosphorylation depending upon the state of differentiation. J. Cell Physiol. In Press
Xu, Y. and Fleet, J.C. (2009) Complete recovery of the VDR knockout phenotype by villin-directed expression of VDR in the intestine. Gastroenterology In Press
- John Anderson
- Ourania Andrisani
- Scott D. Briggs
- Steven S. Broyles
- Ryan Cabot
- Shawn S. Donkin
- Emily Dykhuizen
- James C. Fleet
- Stanton S. Gelvin
- Humaira Gowher
- Tara Henagan
- Chang-Deng Hu
- Joseph M K Irudayaraj
- Michael D. Kane
- Andrea Kasinski
- Ann L. Kirchmaier
- Stephen F. Konieczny
- Sophie A. Lelièvre
- Damon Lisch
- Joseph P. Ogas
- Barbara Stefanska
- Elizabeth J. Taparowsky
- Elizabeth J. Tran
- Vikki Weake
- Clifford F. Weil
- Jer-Yen Yang