application) Mary Waltner-Law received her Ph.D. from Purdue University in 1996 and has been a post-doctoral research fellow in the laboratory of Dr. Daryl Granner at the Vanderbilt University School of Medicine from 1996-present. Dr. Granner's laboratory studies the hormonal regulation of phosphoenolpyruvate carboxykinase (PEPCK) gene expression and Dr. Waltner-Law has been studying the role of signal transduction pathways that mediate the repression of this gene in response to insulin. Dr. Waltner-Law has chosen to expand her research to study two factors, the transcription factor, NF-kappaB, and the corepressor, TLE1. Dr. Waltner-Law's immediate research goals include 1) determining how insulin regulates these factors and 2) identifying genes that are regulated by these factors in response to insulin. This grant will provide Dr. Waltner-Law with the additional mentored research experience necessary to achieve these goals. Information gained from the proposed experiments will enable her to fulfill her long-term goal of establishing independent research in her own laboratory to study the expression of genes encoding metabolic enzymes. By understanding how insulin regulates transcription factors and gene expression, she will be able to identify defective transcriptional processes in metabolic diseases, such as diabetes. Dr. Waltner-Law has proposed to use several techniques that are new to her, including mass spectrometry and perfusion studies in transgenic mice. She has access to the Mass Spectrometry Research Center at Vanderbilt University and will attend classes that will enable to her to identify post-translationally modified sites using mass spectrometry. The facilities and collaborative environment in the Department of Molecular Physiology and Biophysics will allow her to utilize the physiological techniques necessary to answer the questions proposed in this grant. Additionally, Dr. Waltner-Law will have access to the Diabetes Research and Training Center at Vanderbilt, which maintains a number of core labs designed to facilitate diabetes research. The techniques proposed in this grant will be invaluable for Dr. Waltner-Law to study the regulation of transcription and gene expression in the future.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01DK002887-03
Application #
6524095
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Hyde, James F
Project Start
2000-08-15
Project End
2003-07-31
Budget Start
2002-08-01
Budget End
2003-07-31
Support Year
3
Fiscal Year
2002
Total Cost
$85,231
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Physiology
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Prasad, Ratna Chakraborty; Wang, Xiaohui L; Law, Brian K et al. (2009) Identification of genes, including the gene encoding p27Kip1, regulated by serine 276 phosphorylation of the p65 subunit of NF-kappaB. Cancer Lett 275:139-49
Herzog, Birger; Cardenas, Jessica; Hall, Robert K et al. (2006) Estrogen-related receptor alpha is a repressor of phosphoenolpyruvate carboxykinase gene transcription. J Biol Chem 281:99-106
Prasad, Ratna Chakraborty; Herzog, Birger; Boone, Braden et al. (2005) An extract of Syzygium aromaticum represses genes encoding hepatic gluconeogenic enzymes. J Ethnopharmacol 96:295-301
Herzog, Birger; Hall, Robert K; Wang, Xiaohui L et al. (2004) Peroxisome proliferator-activated receptor gamma coactivator-1alpha, as a transcription amplifier, is not essential for basal and hormone-induced phosphoenolpyruvate carboxykinase gene expression. Mol Endocrinol 18:807-19
Waltner-Law, Mary; Duong, David T; Daniels, Marc C et al. (2003) Elements of the glucocorticoid and retinoic acid response units are involved in cAMP-mediated expression of the PEPCK gene. J Biol Chem 278:10427-35
Duong, David T; Waltner-Law, Mary E; Sears, Rosalie et al. (2002) Insulin inhibits hepatocellular glucose production by utilizing liver-enriched transcriptional inhibitory protein to disrupt the association of CREB-binding protein and RNA polymerase II with the phosphoenolpyruvate carboxykinase gene promoter. J Biol Chem 277:32234-42
Waltner-Law, Mary E; Wang, Xiaohui L; Law, Brian K et al. (2002) Epigallocatechin gallate, a constituent of green tea, represses hepatic glucose production. J Biol Chem 277:34933-40