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Predoctoral Trainees-Current
 Nella Barshteyn - June 1, 2007-Present
Pharmaceutical Sciences PhD Candidate
PhD Advisor- Adnan A. Elfarra - School of Veterinary Medicine
Research as of June 2007
My research focuses on characterization of in vitro and in vivo covalent interactions of reactive metabolites of the environmental contaminants trichloroethylene and butadiene with specific amino acid residues on the alpha- and beta-chains of rat hemoglobin. These studies are significant because they will clarify the reactivity and specificity of various nucleophilic groups on the two hemoglobin chains towards reactive metabolites. Specific covalent modifications of blood proteins are also being developed as biomarkers of exposure to these chemicals and as a measure of specific reactive metabolites in the circulation. The latter studies will help clarify mechanisms of extrahepatic toxicity after rat exposure to these chemicals.
Irving, Roy - February 1, 2008 - present
Molecular and Environmental Toxicology PhD Candidate
PhD Advisor- Adnan A. Elfarra - School of Veterinary Medicine
Research as of June 2008
Brittney Jung - May 1, 2007 to Present
Molecular and Environmental Toxicology PhD Candidate
PhD Advisor - Nihal Ahmad - School of Medicine & Public Health
Research 2008 To determine the role of SIRT proteins in prostate cancer. SIRT1 is a conserved NAD-dependent deacetylase that regulates life span in accord with nutritional provision. SIRT1 also down-regulates stress-induced p53 and FoxO pathways for apoptosis, thus favoring survival under stress.
 Kevin Lanham - June 2007 to present
Biomolecular Chemistry PhD Candidate
PhD Advisor Lab of Warren Heideman, PhD
Research as of June 2007
My research is focused on exploring aspects of epigenetic toxicology in the zebrafish heart upon dioxin exposure. Epigenetic toxicology is based upon two principles; the first is that an environmental toxicant can perturb the epigenetic state of a cell and alters its fate, and the second is that the epigenetic state of a cell can dictate how that cell responds to an environmental toxicant.
Zebrafish embryos exposed to dioxin during the first three days post fertilization display signs of cardiovascular toxicity including edema, reduced blood flow, and a stretched string-like heart. Microarray analysis of dioxin exposed embryonic hearts has revealed that a cluster of cell proliferation genes is down regulated within the first twelve hours of exposure. In contrast, juvenile fish exposed to the same dose of dioxin do not develop edema or alterations in heart morphology despite a greater uptake of dioxin. The zebrafish heart continues to proliferate throughout its lifetime, but preliminary microarray data indicates that there is no down regulation of cell cycle genes by dioxin in exposed juveniles. The implication is that the heart undergoes an epigenetic transformation that alters its sensitivity to dioxin.
Comparison of juvenile and embryonic gene expression patterns will provide insight into the mechanism underlying dioxin induced developmental cardiac toxicity. In addition, understanding the epigenetic basis of dioxin sensitivity will tell us more about why particular organ systems and life stages appear to be targeted by environmental toxicants.
Rachel Novick - February 1, 2005 to Present
Molecular and Environmental Toxicology PhD Canddiate
PhD Advisor- Adnan A. Elfarra - School of Veterinary Medicine
 Keelia Rhoads - October 1, 2006 to Present
Molecular and Environmental Toxicology PhD Candidates
PhD Advisor- Lauren A. Trepanier - School of Veterinary Medicine
Research as of September 2007
Carcinogens such as 4-aminobiphenyl (ABP), found in tobacco smoke, and 2-amino-1-methyl-6-phenylimidazo [4,5-b]-pyridine (PhIP), found in grilled meats, can form adducts that initiate cancer. While these adducts have been identified in normal breast and breast cancer tissue as well as the milk of nursing mothers, there still is no consensus on the role that smoking or eating grilled meats may play in the formation of breast cancer. Inconsistent findings could be due to the inability to adequately control for individual differences in the enzymes that metabolize arylamine carcinogens.
Before adduct formation, arylamine carcinogens must be activated to produce hydroxyl amine metabolites, but we have shown that these reactive metabolites can be detoxified by a microsomal reduction pathway containing NADH cytochrome b5 reductase (b5R) and cytochrome b5 (cyt b5). It has been demonstrated that both of these enzymes are present in human breast tissue. The goal of my research is to determine whether the model carcinogen N-OH-ABP is detoxified in breast tissue by cyt b5 and b5R. I also want to determine if differences in DNA adduct formation can be attributed to differential expression or activity of these two enzymes in breast tissue. I also will determine if genetic variability in cyt b5 or b5R affects the susceptibility of acquiring breast cancer in women who are exposed to environmental arylamine carcinogens. It is our hope that these results will provide some explanations for the mixed findings of risk of breast cancer among various epidemiologic studies.
 Echoleah Rufer - September 1, 2006 to Present
PhD Advisor - Susan M. Smith - College of Agriculture and Life Sciences
Research as of Spring 2008
Prenatal alcohol exposure is the leading known cause of mental retardation. Because prevention of alcohol use is difficult there is great interest in therapies that ameliorate alcohol’s damage. The severity of fetal alcohol spectrum disorders (FASD) increases with parity, implying the depletion of a protective maternal factor, perhaps nutritional. Although micronutrient deficiencies (e.g. vitamins, minerals) are common in alcoholics this hypothesis remains largely untested. Because chronic alcohol consumption may alter micronutrient homeostasis, as well as its effects on food choice and intake, there is growing interest in the potential interaction between maternal nutrient status and alcohol-induced fetal injury.
Iron deficiency is the most common single nutrient deficiency in women, affecting 22% of women of child-bearing age (Stoltzfus 2001). Iron inadequacy (ID) strongly correlates with maternal parity (Milman et al. 1992). Importantly, Streissguth et al. (1983) found that 10-20% of alcoholic pregnant women, 50% in the heaviest drinkers, were iron deficient. In human and animal studies, gestational ID produces psychomotor deficits that affect attention, learning and motor skills. These deficits can occur even when overt anemia is absent. Developmental ID causes neurodevelopmental deficits that parallel FASD, thus I hypothesize that ID and alcohol may synergize to heighten alcohol’s neurotoxicity. My first studies focus upon the cerebellum, for which alcohol’s effects are well described.
In addition, I am investigating the teratogenic effects of trichloroethylene (TCE), the most commonly reported groundwater contaminant. Current EPA limits allow a maximum contaminant level of 5 parts per billion (ppb) while actual environmental concentrations range from well below the 5 ppb EPA limit to over 20,000 ppb at superfund sites. Previous research in our lab has shown significant cardiac teratogenic effects in chick embryos after in ovo exposure to concentrations at or near the EPA allowed contamination levels. I have found the critical window of exposure for TCE to be during valvuloseptal morphogenesis in the chick embryo. Embryos exposed during this time exhibit a biphasic doses response curve with survival as an endpoint, with mid-range doses (a concentration of approximately 8 ppb in the egg) being the most lethal and the higher and lower doses having little effect on survival. Echocardiography on hatched chicks surviving TCE exposure shows a significant incidence of ventricular septal defects (38% in treated vs. 0% in control chicks).
 Travis Schmit - July 1, 2007 to Present
Molecular and Environmental Toxicology PhD Candidate
PhD Advisor- Nihal Ahmad - School of Medicine & Public Health - Dept of Dermatology
Research as of May 2006
The focus of my research is to explore the involvement of the Polo-like kinases (Plks), a conserved serine/threonine family of kinases critical for mitosis regulation, in the development of cancer. Many environmental stresses (such as shifts in temperature, osmolarity, radiation and chemicals) may lead to problems with actin cytoskeleton and cytokinesis, and Plks have been shown to be critical regulators of these processes. Further, a major hallmark of cancer is the dysregulation of key cell cycle components arising from mutations produced by environmentally induced oxidative stress and the resulting DNA damage. These include tumor suppressor genes that, when mutated, are unable to control cell cycle checkpoints and allow the cell to proliferate unchecked, or oncogenes which become constitutively active and promote cellular growth. The Plk family of mitotic kinases contains both members that can act in an oncogenic manner and members that act as tumor suppressors.
I am studying the role of Plk1 and Plk3 in cancer development. Plk1, the most widely studied member of this kinase family, promotes Cdk1/CyclinB1 activity which is the main driving force into and through mitosis. Conversely, Plk3 acts in an inhibitory manner in the presence of DNA damage opposing the activity of Plk1 and halting cell cycle progression until repair is performed or the cell undergoes apoptosis. Thus, my focus is to determine the role of the Plks in cancer development and to establish if their dysregulation has a cause-and-effect association with disease progression. The outcome of this work may lead to development of novel strategies for the management of cancer.
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