Research in Toxicology

Dr. Jason Cannon's research interests include neurodegeneration, neurotoxicology, and gene-environment interactions.  The majority of human diseases are thought to arise from interactions between environmental factors, genetic susceptibility, and aging.  The interplay between these factors is particularly important in neurodegenerative diseases, including Parkinson’s disease.  My laboratory primarily studies the contribution environmental exposures have in neurodegeneration and the importance of gene-environment interactions. We are exploring the role these interactions may play in disease pathogenesis. The information we have learned about these important interactions may also be used to design and test new potentially therapeutic approaches.  Specific projects include:  1) Creation of new gene-environment interaction models of neurodegeneration; 2) Characterization of newly created transgenic rat models of Parkinson’s disease; 3) Heterocyclic amine exposure and neurodegeneration; and 4) Acute pesticide exposure during development and late-life neurological dysfunction.  The major techniques utilized in my lab are:  neurobehavioral analysis, stereotaxic infusion, gene therapy/viral vector-mediated gene transfer, neurochemistry (HPLC w/electrochemical detection) and histology/microscopy.

Dr. Ulrike Dydak 's research interest is the methodological development and application of magnetic resonance imaging (MRI) to study human health. In particular she uses Magnetic Resonance Spectroscopy (MRS) for the noninvasive in-vivo assessment of metabolism to investigate neurodegeneration, influences of toxins, and to monitor treatment response. Special emphasis of her work lies on the development of the in-vivo detection and quantification of γ-aminobutyric acid (GABA), an inhibitory neurotransmitter, to study manganese-induced parkinsonian neurotoxicity and idiopathic Parkinson Disease. A second focus lies on the development of whole-liver phosphorous (31P) magnetic resonance spectroscopic imaging of the human liver to improve treatment monitoring in liver cancer. Dr. Dydak holds an adjunct appointment at the Department of Radiology and Imaging Sciences at IU School of Medicine, where part of her research lab is located.

Dr. Jennifer Freeman's research interests are in molecular and environmental toxicology, cytogenetics, genomics, and epigenomics. Current research efforts in the Freeman laboratory are focused on investigating the adverse health effects of exposure to environmental stressors on human and environmental health using the zebrafish model system. The zebrafish is a prominent model system in a variety of biological disciplines and has become one of the preferred vertebrate models in biomedical research. Similarities between the zebrafish and human genome permits investigations into the molecular pathways found to play a role in the mechanisms of toxicity in the zebrafish and translation to humans. Dr. Freeman has been involved in the cytogenetic mapping of the zebrafish genome in efforts to establish an accurate and comprehensive genome sequence. She also developed the first array comparative genomic hybridization platforms for the zebrafish that were applied to investigate genomic imbalances in zebrafish developmental mutant and disease models including numerous cancer models. In addition, these platforms were applied to define and characterize copy number variants (CNVs) in the zebrafish genome.  Ongoing research projects in the Freeman laboratory are defining the underlying genetic and epigenetic mechanisms of toxicity of environmental stressors with current focus on pesticides, metals, and radiation. Three major ongoing projects are investigating the underlying genetic and epigenetic mechanisms of toxicity of a developmental exposure to (1) the heavy metal lead, (2) the herbicide atrazine, and (3) radiation. These projects are identifying genetic biomarkers and molecular pathways of the immediate adverse impacts of a developmental exposure, the lasting impacts of this developmental exposure throughout the lifespan, and the analysis of subsequent generations linking genetic, epigenetic, and phenotypic assessments. These studies are investigating a developmental origin of adult disease pathogenesis with a specific focus on neurodegenerative disorders, cancer, and reproductive alterations.

Dr. Linda H. Nie's research focuses on two integrated areas. One is on instrumentation development. In this line of research, her group has developed instruments and technologies for noninvasive, real-time in vivo quantification and distribution of elements in human body and for diagnose and treatment of diseases. Currently her group is working on four projects in this area: 1) development and validation of a transportable neutron activation analysis technology for in vivo quantification of metals in human bone; 2) development and validation of a portable x-ray fluorescence technology for in vivo quantification of metals in human tissues; 3) development and validation of an associated particle neutron imaging technology for medical applications related to elemental distributions and alterations; and 4) development of a DD compact neutron generator based boron neutron capture therapy (BNCT) system.  The second area of Dr. Nie’s research focus is to apply the novel instruments developed in her group to the field of medicine and health sciences. Her group is currently working on three projects in this direction: 1). childhood lead (Pb) poison study on the association between Pb exposure and psychological effects for children, in collaboration with researchers at Xinhua Hospital affiliated to Shanghai Jiaotong University in China, using the bone Pb measurement technologies developed in her group; 2) a collaborative study to investigate association between Mn exposure and neurological outcomes using the new in vivo neutron activation analysis (IVNAA) technology being developed in her group, together with researchers from School of Health Sciences at Purdue University and the researchers at Zunyi Medical University in China; and 3) a collaborative study on a project related to association between lead exposure and neurodegeneration, together with researchers at Harvard School of Public Health and Rush Medical Institute.

Dr. Jonathan Shannahan’s research interests include immune responses to engineered nanomaterials, environmental toxicology, nanoparticle-biological interactions, and susceptible subpopulations.  The emerging field of nanoscience has the capability to revolutionize countless technologies.  Engineered nanomaterials due to their extremely small size and distinct programmable properties can transform numerous consumer products, manufacturing processes, and biomedical applications.  With the expanded use of nano-enabled products and technologies human exposures are increasing in environmental, occupational, and consumer settings. In order for the safe and effective usage of engineered nanomaterials it is necessary to evaluate possible toxicity prior to introduction into the population.  Early toxicological evaluation can reduce cost of engineered nanomaterial developmental, for nanotherapeutics enhance pharmaceutical benefits, and also reduce unintended adverse health effects. Further studies of toxicity are often performed in healthy models that do not represent realistic human exposures which consist of numerous susceptible subpopulations.  Dr. Shannahan investigates nanoparticle-induced mechanisms of toxicity using cell culture and animal models as well as –omics approaches.  Specific projects include: 1) Nanoparticle interactions with disease environments resulting in deferential cellular responses, 2) Utilization of proteomics and metabolomics to identify biomarkers of exposure and toxicity, 3) Disease-related cellular phenotypic alterations and their impact on nanoparticle-induced responses, 4) Assessment of nanoparticle physicochemical properties on cardiopulmonary and immune toxicity.  Overall the goals of Dr. Shannahan’s research are to understand nanomaterial biological interactions and responses in order to maximize the potential benefits of nanotechnology while avoiding possible adverse health effects.

Dr. Ellen Wells conducts environmental epidemiology studies exploring how exposure to metals or endocrine disruptors impacts cardiometabolic and neurologic health.  Much of her work focuses on children’s environmental health and how early life exposures may impact health in later life.  She has conducted extensive work looking at the relationship of metal exposure during pregnancy with cardiovascular risk factors, including work which identified an association of lead exposure with blood pressure at very low exposure concentrations.  She has also conducted research related to metabolic and other health impacts resulting from children’s exposure bisphenol A and related compounds.  Her new projects focus on improving our understanding of the neurologic impact of occupational exposure to multiple metals among welders and smelters from Indiana and China.

Dr. Wei Zheng's conducts research related to toxic metal-induced neurodegenerative disorders:   The overarching research theme in my laboratory is to understand the mechanisms underlying metal-induced neurotoxicities with a particular focus on the roles of brain barrier systems in regulating metal homeostasis in brain.  The major discoveries made since my time at Columbia University (1993-2003) and now at Purdue University (2003-present) include: (1) the original discovery that lead (Pb) accumulation in brain choroid plexus reduces the production of transthyretin (TTR) and hinders the transport of thyroid hormones into brain, which may contribute to Pb-induced brain developmental defects; (2) the original research that unveils the molecular mechanism by which iron (Fe) and copper (Cu) are transported in and out of brain by brain barrier systems and how exposure to manganese (Mn) alters these processes, leading to Mn-induced parkinsonism; (3) the novel approach by applying synchrotron X-ray fluorescence technique to establish a distinct role of Pb in the formation of amyloid plaques in the pathoetiology of Alzheimer’s disease in transgenic animal models; and (4) the discoveries of novel biomarkers for Mn and Pb exposure in human cohorts of smelters, welders and battery workers. Current research activities are focused mainly on two areas of laboratory investigations, i.e., (1) the role of Cu in adult neurogenesis and how the interaction between Mn and Cu may adversely affect the processes, contributing to Mn-induced Parkinsonian disorder, and (2) how Pb exposure alters the transport and homeostasis of β-amyloid in brain. The lab has also had established collaborations with epidemiologists, medical engineers and public health workers in conducting human studies in occupational and environmental settings. The research in my lab has been supported by NIH grants (since 1994), U.S. Department of Defense contracts, and other awards from pharmaceutical companies such as Johnson & Johnson and Eli Lilly.

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