The objectives of the Molecular Mechanisms of Toxicity Training Program are to provide trainees with an education in the cellular and molecular mechanisms by which environmental agents induce human disease. The training program is based on an understanding of biochemistry, molecular/cell biology, pharmacology, and toxicology, and is coupled with in-depth laboratory research training. The Training Program is based in the Graduate Center for Toxicology (GCT), a basic science department in the College of Medicine that grants the Ph.D. in Toxicology and provides an administrative and teaching nucleus of 11 Core Faculty. Joint faculty from Medicine, Pharmacy, Agriculture, and Arts &Sciences enrich the diversity of training opportunities;25 of these Core and Joint Faculty with strong research programs make up the Training Grant Faculty. This competitive renewal application requests support for 4 pre- and 2 postdoctoral trainees;it is focused on three disease areas with an environmental basis: Cancer, Cardiovascular Disease and Neurodegenerative Disease. Oxidative stress and DNA damage and repair are mechanistic themes that underlie many of the research programs, providing opportunities for collaborations and multidisciplinary approaches that enrich the research training. The pre-doctoral training program requires biomedical (25 credits) and toxicology bases (13 credits) and an elective (2-4 credits). Pre-doctoral trainees will be supported for a maximum of 3 years (e.g., years 2-4 of doctoral training;Postdoctoral trainees will be supported for a minimum of 2 years. Ph.D. fellows will be recruited within 3 years of their degree, while M.D. fellows will be recruited upon completion of their residency training;the investigators anticipate a ratio of 2 Ph.D.s to 1 M.D. Postdoctoral trainees are required to enroll and participate in 2 credits of Environmental Exposure and Human Disease in addition to a rigorous laboratory experience. Currently, 28 students are enrolled in the Toxicology Ph.D. program, including 6 minority students, most of whom were recruited from the University of Puerto Rico and supported by summer research/education grants. The University provides strong support for the GCT in the form of student fellowships, supplementation to this Training Grant, and faculty lines, space and equipment to enhance and sustain a strong toxicology program. Relevance: The Training Program in Molecular Mechanisms of Toxicity will provide pre- and postdoctoral fellows with a fundamental understanding of the molecular and cellular processes by which environmental agents impact human health and cause disease. The long-term goal is to prepare and inspire the next generation of scientists to address the ever-present environmental challenges to human health by the prevention of disease, either by nutritional intervention or by otherwise exploiting human defense systems.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Institutional National Research Service Award (T32)
Project #
5T32ES007266-23
Application #
8296301
Study Section
Environmental Health Sciences Review Committee (EHS)
Program Officer
Shreffler, Carol K
Project Start
1990-07-01
Project End
2015-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
23
Fiscal Year
2012
Total Cost
$227,299
Indirect Cost
$17,460
Name
University of Kentucky
Department
Pharmacology
Type
Schools of Medicine
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40506
Holley, Aaron K; Xu, Yong; Noel, Teresa et al. (2014) Manganese superoxide dismutase-mediated inside-out signaling in HaCaT human keratinocytes and SKH-1 mouse skin. Antioxid Redox Signal 20:2347-60
Jarrett, Stuart G; Wolf Horrell, Erin M; Christian, Perry A et al. (2014) PKA-mediated phosphorylation of ATR promotes recruitment of XPA to UV-induced DNA damage. Mol Cell 54:999-1011
Holley, Aaron K; Miao, Lu; St Clair, Daret K et al. (2014) Redox-modulated phenomena and radiation therapy: the central role of superoxide dismutases. Antioxid Redox Signal 20:1567-89
Miao, Lu; Holley, Aaron K; Zhao, Yanming et al. (2014) Redox-mediated and ionizing-radiation-induced inflammatory mediators in prostate cancer development and treatment. Antioxid Redox Signal 20:1481-500
Newsome, Bradley J; Petriello, Michael C; Han, Sung Gu et al. (2014) Green tea diet decreases PCB 126-induced oxidative stress in mice by up-regulating antioxidant enzymes. J Nutr Biochem 25:126-35
Edwards, Deanna N; Machwe, Amrita; Wang, Zhigang et al. (2014) Intramolecular telomeric G-quadruplexes dramatically inhibit DNA synthesis by replicative and translesion polymerases, revealing their potential to lead to genetic change. PLoS One 9:e80664
Edwards, Deanna N; Orren, David K; Machwe, Amrita (2014) Strand exchange of telomeric DNA catalyzed by the Werner syndrome protein (WRN) is specifically stimulated by TRF2. Nucleic Acids Res 42:7748-61
Son, Young-Ok; Hitron, John Andrew; Cheng, Senping et al. (2011) The dual roles of c-Jun NH2-terminal kinase signaling in Cr(VI)-induced apoptosis in JB6 cells. Toxicol Sci 119:335-45
Miriyala, Sumitra; Holley, Aaron K; St Clair, Daret K (2011) Mitochondrial superoxide dismutase--signals of distinction. Anticancer Agents Med Chem 11:181-90
Athippozhy, Antony; Huang, Liping; Wooton-Kee, Clavia Ruth et al. (2011) Differential gene expression in liver and small intestine from lactating rats compared to age-matched virgin controls detects increased mRNA of cholesterol biosynthetic genes. BMC Genomics 12:95

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