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Toxicology Research

Toxicology research spans an array of topics ranging from the molecular in population level consequences of toxicant exposure.  Research in the Toxicology Program at NC State University is conducted in many key toxicological areas including but not limited to; fundamental mechanisms, GxE interactions, resistance and susceptibility to environmental stressors, effects of the environment on the genome and epigenome, individual and population susceptibility, critical windows of susceptibility, endocrine disrupting chemicals, integration of high-throughput screens, cell systems, and model organisms to identify fundamental mechanisms.

There is increasing awareness that there are strong linkages between environmental quality and health. The One Health concept recognizes that the health of humans, animals and the environment are interconnected, and promotes the expansion of interdisciplinary approaches and collaborations.  Research at NCSU embraces the One Health philosophy by seeking to understand the fate and effects of contaminants in the environment. Specific research interests include the behavior of contaminants in the environment, the movement of contaminants in food webs that may ultimately lead to human exposures and the reduction of contaminant exposures to people and ecosystems via remediation.

A weekly research Seminar Series provides a forum for invited scientists and graduate students/postdocs to present and discuss their research.  Each semester a former student is invited back to present a seminar and to share their career experiences with current students and postdocs.

Research Focus Areas and Brief Description of Individual Faculty Research Interests

Toxicology Program faculty have been grouped into six key research areas:

Students will receive state of the art research training in one of the laboratories described below. While faculty are grouped into five research foci, it is important to note that there are faculty:faculty, faculty:trainee and trainee:trainee interactions within and between the various key research foci.

Critical Windows of Susceptibility

Faculty Research Description
 Scott Belcher The research in the Belcher Lab centers on defining the role of estrogen during development and understanding the pathological impacts of endocrine disrupting chemicals. His research interests center around defining the molecular, cellular, and physiological mechanisms that regulate the developmental actions of estrogens and endocrine disruptors in the heart and developing brain. Current research using transgenic/knockout mouse models of human disease and a variety of in vitro approaches is focused primarily on mechanisms involving estrogen receptor signaling that influence development of the cerebellum, cardiac pathology and estrogen-responsive growth of childhood brain tumors.
Michael Cowley The Cowley Lab aims to understand how environmental stressors can impact phenotype by causing alterations to the epigenome. As a model for environment/epigenome/phenotype interactions, the Cowley Laboratory is studying the effects of parental diet on offspring development and the programming of life-long health using mouse models.
Seth W. Kullman The Kullman Lab uses molecular, computational, and comparative/functional genomic approaches to examine how exposure to environmental stressors (dys) regulate complex interactions between genotype and phenotype. The laboratory is particularly interested in endocrine pathways that govern critical steps in developmental process, embryonic development and organization.
Heather Pautisaul The Patisaul Lab explores the mechanisms by which exposure to endocrine disruptors, during critical windows of development, impacts neuroendocrine pathways in the brain related to sex specific physiology and behavior. Compounds of interest in her laboratory include BPA, phytoestrogens, and the fire retardant mixture, Firemaster 550.
Antonio Planchart The Planchart Lab is interested in GxE interactions as it relates to developmental toxicology and is studying dioxin-induced jaw malformations using a zebrafish model. The Planchart Laboratory is exploring a novel mechanism by which the ubiquitous environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin perturbs vertebrate cranifacial development.
Nanette Nascone-Yoder  The Nascone-Yoder Lab studies the molecular and cellular mechanisms underlying left-right asymmetric gut morphogenesis. Intestinal malrotation is a potentialy lethal disorder that occurs in 1 in 500 newborns. Both environmental and genetic factors are believed to contribute to the incidence of intestinal malrotation but the etiology remains elusive.
Emilie Rissman The Rissman Lab research is in the field of behavioral neuroendocrinology focuses on how hormones and environmental chemicals affect behavior and the brain. The Rissman Laboratory research group is examining how endocrine disruptor chemicals, which interfere with hormone systems and can cause disabilities in social behaviors and other developmental disorders, alter brain development and behavior over generations.
Marcelo Rodriguez-Puebla The Rodriguez-Puebla Lab is interested in understanding the effect of in utero arsenic exposure on keratinocytes stem cells (KSCs) in the offspring as adults and its association with the increase rate of maligant progression observed in skin tumors.

Ecotoxicology and One Health

Faculty Research Description
W. Gregory Cope The Cope Lab’s research interests are in aquatic toxicology, ecology, and physiology, as well as in the transport, fate, and effects of aquatic pollutants and other human-mediated stressors such as temperature and climate change. This research utilizes sentinel aquatic organisms, biomarkers of exposure, effect, or susceptibility, or alternative toxicological models from which linkages to environmental and human health are evaluated.
Michael Hyman The Hyman Lab is interested in bioremediation with projects involving the biochemistry and physiology of soil nitrifying bacteria. These unusual organisms are responsible for initiating the oxidation of ammonia within the nitrogen cycle. This activity is important in wastewater treatment processes and in determining the environmental effects of agricultural fertilizer use. The second area of research focuses on the process of microbial cometabolism. This activity underlies many of the aerobic processes involved in the bioremediation of recalcitrant compounds such as chlorinated solvents.
Elizabeth Nichols The Nichols Lab is interested in how trees, in natural or managed systems, mitigate and remove contaminants and pollutants in soil and groundwater. The lab is also interested in water quality issues and the protection of surface water and groundwater resources. They use isotopic analyses to understand water resource use by trees, fate of contaminants in vegetated systems, and the use of trees to monitor and track subsurface contamination.
R. Michael Roe The research in the Roe Lab involves research and development of polymers for the stabilization and delivery of therapeutic proteins, nucleic acids and pesticides to their site of action in animal and plant systems; transition state analog chemistry of insect metabolic systems including esterases, epoxide hydrolases and juvenile hormone synthesis; development of high throughput RNAi screening methods and screening for the development of novel insecticide targets; development of novel traditional and transgenic pest control technologies and applications in material science; development of insect repellents; microbiomics associated with human pathogenesis; neurogenomics of tick and mite sensory systems and host interaction; and study of the global molecular impact of environmental chemicals on primary human cells, the role of lncRNA and microRNA in this impact, and risk assessment for workers and the public.
Michael Stoskopf The Stoskopf Lab focuses on population, ecosystem and landscape approaches to health management of wildlife species broadly defined to include aquatic and marine species including invertebrates and vertebrates. Most of the graduate students in the laboratory are focused on the application of advanced NMR/MRI/S techniques to key questions in ecological metabolomics, primarily related to impacts of global change. Impacts of temperature and ocean acidification on physiology are of particular interest as well as habitat health risk assessment questions primarily for endangered species recovery decision making.

Reactive Oxygen Species (ROS)-Induced Toxicity/Disease

Faculty Research Description
Jun Ninomiya-Tsuji The Ninomiya-Tsuji Lab is interested in the kinase cascade-mediated regulation of reactive oxygen species (RO) metabolism associated with inflammatory diseases.  The Ninomiya-Tsuji Laboratory has identified TAK1 kinase cascade as a key regulatory pathway of ROS metabolism in the skin, intestinal epithelium and macrohages.  Current students in the laboratory are aimed at the elucidation of (1) the molecular mechanism by which TAK1 kinase regulates ROS, and (2) the molecular mechanism that links environmental stress-TAK1 pathway with inflammatory conditions in epithelial tissues.
Yoshiaki Tsuji The Tsuji Lab is focused on how ROS is involved in gene regulation and on cellular antioxidant defense systems in environmental stress conditions.  The Tsuji Laboratory research is focused on the molecular mechanism by which the human ferritin gene, the major iron storage and detoxification role, is transcriptionally regulated under oxidative stress conditions induced by such agents as arsenic.

Human Population Science

Faculty Research Description
Michael Bereman The Bereman Lab’s central focus of research is to develop innovative, quantitative methodologies to investigate the interplay between environmental and genetic factors with respect to the impact on human health and disease.  The Bereman Laboratory is particularly interested in the role of environmental factors in amyotrophic lateral sclerosis (ALS).
 Jane Hoppin  Dr. Hoppin is an environmental epidemiologist whose research focuses on the human health effects of pesticides and other agricultural exposures with primary focus on respiratory and allergic outcomes.
 Cathrine Hoyo  Dr. Hoyo is a molecular epidemiologist and her research program is focused on examining genetic, epigenetic and environmental causes of common chronic diseases and conditions such as obesity, diabetes and cancer across the life course, with  a thrust on how prenatal exposures permanently shift the epigenome and alter the risk of common chronic diseases in the offspring.

Resistance and Susceptibility to Environmental Stressors and GxE Interactions

Faculty Research Description
James C. Bonner,
Director of Graduate Programs
The Bonner Lab aims at understanding the molecular mechanisms of nanoparticle-induced respiratory disease in mice (fibrosis, asthma, cancer) in order to predict the impact of emerging nanotechnologies on human health and thereby prevent disease.
Kenneth Adler The Adler Lab is interested in elucidating the pathogenic and environmental mechanisms associated with inflammation in the respiratory airways.  The Adler Laboratory research revealed that the MARCKS protein was a key regulator of airway mucus secretion and inflammation, and he developed a novel reagent in his laboratory that could inhibit MARCKS and decrease mucus and inflammation in vitro and in animal models of asthma and bronchitis.
Robert Anholt The Anholt Lab is focused on whole genome transcriptional analyses and the incorporation of state-of-the-art genomic strategies in studies on a wide range of phenotypes, with special interests in the genetic underpinnings of phenotypic plasticity and genotype-environment interactions using systems approaches. The Anholt Laboratory is studying variation in genetic susceptibility to the effects of oxidative stress, alcohol and lead exposure in the powerful genetic Drosophila model.
David Aylor The Aylor Lab uses the Collaborative Cross (CC) mouse reference population to study the genetic basis of differential susceptibility to EDCs with reproductive system as the readout. The CC consists of hundreds of independently bred, recombinant inbred lines of mice that will enhance quantitative trait locus and systems genetic analyses. The Aylor Laboratory research program combines genetics, genomics, bioinformatics, mammalian reproduction, and toxicology.
Matthew Breen The Breen Lab focuses on genomics, genome mapping and the comparative aspects of canine cancer. In addition his lab is using high throughput molecular cytogenetics for anchoring emerging genome assemblies and for evaluating the changes to genome structure that occur during speciation. The lab is also developing new molecular assays for diagnostic and prognostic use in veterinary medicine.
David Buchwalter  The Buchwalter Lab explores comparative invertebrate ecophysiology,  trace metal bioaccumulation and detoxification, and more recently, thermal physiology. A major goal of our work is to better understand how and why species are differentially responsive to environmental stressors such as trace metals and other ions, and thermal stress. The Buchwalter Laboratory primarily works with field collected insect populations, though we are developing a mayfly (Centroptilum triangulifer) as a model organism.
Gerald LeBlanc The LeBlanc Lab’s research involves the elucidation of signaling cascades that are involved in transducing environmental signals (photoperiod, diet, etc.) that regulate physiological processes and their disruption by environmental chemicals.  Studies focus primarily upon the responsiveness and role of nuclear hormone receptors and b-HLH PAS proteins in these signaling cascades.
Trudy Mackay  The Mackay Lab  research is to transform our understanding the genetic basis of quantitative traits from complex statistics to complex genetics, and to identify individual genes and genetic networks affecting quantitative traits, their effects in different environments, and the nature of molecular polymorphisms associated with naturally occurring variation.
Robert Smart The research in the Smart Lab involves the identification and characterization of genes/signaling pathways that are determinants of susceptibility to cancer, particularly as it relates to gene-environment interactions.  We utilize genetic/molecular/cellular-based systems and powerful genetically engineered mouse models to define mechanisms by which environmental stressors induce cancer.  We are especially interested in how cells respond to DNA damage to maintain genomic integrity and the role of the basic leucine zipper transcription factors, CCAAT/enhancer binding proteins (C/EBPs) and long noncoding RNAs in this process.

Computational Toxicology

Faculty Research Description
Ronald Baynes The Baynes Lab current research activities are focused on assessing the dermal disposition of cutting fluid and jet fuel additives and pesticides. This research is providing some understanding of the physicochemical factors influencing dermal absorption of these pesticides and formulation additives that cause occupational irritant dermatitis. Other work is focused on understanding transdermal delivery of avermectins across skin various food animal species. HPLC and GC analytical methods are continually being developed.
Denis Fourches The Fourches Lab’s central research goal is to analyze, model, and forecast complex interactions between chemical structures and various types of biological targets to design novel compounds with the desired activity and safety profiles.
Carolyn Mattingly The Mattingly Lab aims to understand the effects of environmental chemicals on development and human health through the combinatorial use of bioinformatics and experimental models. Since 2001, she has been directing development of the publicly available CTD (http://ctdbase.org/), which provides integrated data about cross-species chemical-gene/protein interactions and chemical- and gene-disease relationships (ES014065).
 David Reif  The Reif Lab’s research focuses on analytical methods development, visualization, and software to integrate high-dimensional genetic and environmental health data. The Reif Laboratory overarching research goal is to understand the complex interactions between human health and the environment through the analysis of high-dimensional data from diverse sources.
 Fred Wright  The Wright Lab interests include gene mapping, methodology development in the statistical analysis of expression microarrays, somatic genomics of cancer, genome-wide association studies, GxE interactions and expression quantitative trait locus (eQTL) analysis.