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.

National Institute of Health (NIH)
National Institute of Environmental Health Sciences (NIEHS)
Institutional National Research Service Award (T32)
Project #
Application #
Study Section
Environmental Health Sciences Review Committee (EHS)
Program Officer
Shreffler, Carol K
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Kentucky
Schools of Medicine
United States
Zip Code
Kamelgarn, Marisa; Chen, Jing; Kuang, Lisha et al. (2018) ALS mutations of FUS suppress protein translation and disrupt the regulation of nonsense-mediated decay. Proc Natl Acad Sci U S A 115:E11904-E11913
Sun, Ramon C; Fan, Teresa W-M; Deng, Pan et al. (2017) Noninvasive liquid diet delivery of stable isotopes into mouse models for deep metabolic network tracing. Nat Commun 8:1646
Kuang, Lisha; Kamelgarn, Marisa; Arenas, Alexandra et al. (2017) Clinical and experimental studies of a novel P525R FUS mutation in amyotrophic lateral sclerosis. Neurol Genet 3:e172
Scott, Timothy L; Wicker, Christina A; Suganya, Rangaswamy et al. (2017) Polyubiquitination of apurinic/apyrimidinic endonuclease 1 by Parkin. Mol Carcinog 56:325-336
Zhao, Y; Carroll, D W; You, Y et al. (2017) A novel redox regulator, MnTnBuOE-2-PyP5+, enhances normal hematopoietic stem/progenitor cell function. Redox Biol 12:129-138
Burikhanov, Ravshan; Hebbar, Nikhil; Noothi, Sunil K et al. (2017) Chloroquine-Inducible Par-4 Secretion Is Essential for Tumor Cell Apoptosis and Inhibition of Metastasis. Cell Rep 18:508-519
Pratheeshkumar, Poyil; Son, Young-Ok; Divya, Sasidharan Padmaja et al. (2017) Quercetin inhibits Cr(VI)-induced malignant cell transformation by targeting miR-21-PDCD4 signaling pathway. Oncotarget 8:52118-52131
Keogh, Norma; Chan, Kara Y; Li, Guo-Min et al. (2017) MutS? abundance and Msh3 ATP hydrolysis activity are important drivers of CTG•CAG repeat expansions. Nucleic Acids Res 45:10068-10078
Holcomb, Nathaniel; Goswami, Mamta; Han, Sung Gu et al. (2017) Inorganic arsenic inhibits the nucleotide excision repair pathway and reduces the expression of XPC. DNA Repair (Amst) 52:70-80
Wang, Lei; Fan, Jia; Hitron, John Andrew et al. (2016) Cancer Stem-Like Cells Accumulated in Nickel-Induced Malignant Transformation. Toxicol Sci 151:376-87

Showing the most recent 10 out of 91 publications