Environment, inflammation, and genes in Alzheimer’s disease-a metabolomics view
Dr. William Hu, Emory University
The pathogenic markers of Alzheimer’s disease (AD) have been widely hypothesized to accumulate in the brain up to 15 years before the onset of cognitive symptoms. AD risks are best modeled by assessing the interaction of demographic factors (age, gender, race), genetic risk factors, active biological processes (e.g. neuroinflammation) and neuroprotective factors (e.g. education). Through complementary genomic, proteomic and metabolomics studies, Dr. Hu hypothesizes that they can enhance the characterization of pre-symptomatic and symptomatic AD. The goal of this pilot project is to validate preliminary observations of environmental chemical and endogenous metabolic changes observed in AD with an independent cohort, develop cerebrospinal fluid metabolomics profiles in the same subjects, and model interaction between GWAS loci for AD, CSF amyloid and Tau proteins, CSF inflammatory proteins, and CSF and plasma metabolomes with special attention to identified environmental chemicals.
Dr. Hu is a professor in the Department of Neurology at the School of Medicine at Emory. His research focuses on developing biochemical markers for neurodegenerative disorders and characterizing the relationship between these biomarkers and brain pathology.
Playing with fire: High-content assays to investigate the role of flame retardant-induced neuroinflammation and neurotoxicity in PD etiology
Dr. Michael Caudle and Dr. Malu Tansey, Emory University
Environmental toxicants, such as flame retardants have been identified as significant risk factors for the development of idiopathic Parkinson’s disease (PD). Flame retardants, including polychlorinated biphenyls (PCBs) and polybrominateddiphenyl ethers (PBDEs), have been used for over 70 years to reduce the flammability of many products. These compounds easily leach into the environment, persist for decades, and are absorbed in human tissue, particularly the brain. Epidemiologic studies identified that PCBs cause significant damage to the nigrostriatal dopamine system, leading to increased risk of PD. Due to the identified health risks of traditional flame retardants, many are no longer used. New flame retardants have been developed to replace them but these actually have the same physiochemical properties of PCBs and PBDEs that made the traditional flame retardants neurotoxic. The goal of this pilot project is to use high-content screening assays to identify the mechanisms through which these new flame retardants promote dysfunction of the nigrostriatal dopaminergic system.
Dr. Caudle is a professor in the Department of Environmental Health at the School of Public Health at Emory. His research focuses on the contribution of exposure to environmental contaminants to the development of neurobehavioral and neurodegenerative diseases, such as Parkinson’s disease, autism, and schizophrenia.
Dr. Tansey is a professor in the Department of Physiology at the School of Medicine at Emory. Her research focuses on the mechanisms of TNF-dependent neuroinflammation and neurotoxicity and their role in etiology and progression of Parkinson’s Disease, gene-environment interactions in the etiology of idiopathic neurodegenerative diseases and other cellular and molecular mechanisms related to neurodegenerative diseases.
The human airway ecosystem: metabolomics and trace element profiling to track complex exposures in chronic and acute disease
Dr. Rabindra Tirouvanziam, Emory University
Cystic Fibrosis (CF) is a fatal genetic disease in which bacterial and/or fungal microbiota and inflammation contribute to an evolving airway ecosystem. Although there are many symptoms due to CF, airway disease, due to a combination of inflammation, obstruction and microbial colonization, is the primary cause of morbidity and mortality. Changes in the human airway ecosystem can impact systemic circulation, causing changes in plasma and serum composition. Inhaled microbes and particulates interact with host epithelial and immune cells, sometimes leading to chronic and acute disease. The goal of this project is to establish a robust pipeline for high-resolution metabolomics and trace element profiling of human airway fluid to allow explorations of the complex exposures that shape the human airway ecosystem. Through analyzing airway fluid samples from various diseases, such as CF, critical steps in the evolution of the airway ecosystem can be assessed by looking for significant changes in the metabolic and trace element profile of the airway fluid.
Dr. Tirouvanziam is a professor in the Department of Pediatrics at the School of Medicine at Emory. His research focuses on mechanisms of innate immunity in humans and their relations to chronic human disease, with emphasis on target identification for the development of novel therapies.
Dr. Christine Payne, Georgia Institute of Technology
Environmental factors such as radiation, asbestos, and heavy metals are well-known for their importance in human disease. Recently, the increased use of nanoparticles in manufacturing consumer products (e.g. paints, cosmetics, ceramics, etc.) has made it important to consider how exposure to nanoparticles affects human health. Titanium dioxide nanoparticles are widely used as a pigment and UV-resistant material. Previous work has identified oxidative stress as a common cellular response to nanoparticles, leading to nanotoxicity. Since oxidative stress in cells is a complex network, this pilot project will use a combination of experiments and systems-level modeling to determine how titanium dioxide nanoparticles affect the redox regulatory network of cells at the level of gene expression. Oxidative stress is particularly important in relation to titanium dioxide nanoparticles as these particles produce reactive oxygen species which are a major contributor to nanotoxicity and are produced in response to UV activation in biological systems. Rather than looking at a single pathway, this pilot project will approach the redox environment of the cell as an entire network.
Dr. Payne is a professor in the School of Chemistry and Biochemistry at Georgia Tech. Her research focuses on understanding the underlying molecular mechanisms by which cells interact with synthetic materials. This includes nanoparticle-cell interactions and conducting polymer-cell interactions along with the development of fluorescence microscopy techniques to address these questions.
Dr. Andrea Winquist, Emory University, and Mr. Yomi Noibi, ECO-Action
The English Avenue and Vine City Neighborhoods in Atlanta are part of the Proctor Creek Watershed and have historically experienced frequent flooding due to rain water runoff and sewer overflows. Atlanta sewer system improvements have decreased the number of sewage spills in the Proctor Creek Watershed, but contamination of creek water with sewage continues, and area residents have regularly expressed concerns about potential health impacts. The goal of this project is to conduct a survey of residents of flood-prone areas in English Avenue and Vine City relating to residential environmental conditions and health outcomes that may be caused or exacerbated by flooding, indoor dampness and mold. Additionally, survey findings will be disseminated to the community, along with educational materials related to potential health effects of flooding and mold and appropriate interventions, to increase environmental heath literacy among community residents . Finally, this study proposes to facilitate development of action plans, based on the findings of the pilot study and input from the community, to further address community concerns relating to the health effects of flooding in the area and increase the capacity of area residents to engage in environmental health research. All research was conducted in close collaboration with the HERCULES Community Outreach and Engagement Core.
Results from this study were published in the Journal of Environmental and Public Health (Eiffert S et al., “A Citizen-Science Study Documents Environmental Exposures and Asthma Prevalence in Two Communities,” vol. 2016, Article ID 1962901, 2016. doi:10.1155/2016/1962901).
Dr. Winquist is a professor in the Department of Environmental Health at the School of Public Health at Emory with interests in health disparities and environmental health.
Mr. Noibi runs Atlanta-based non-profit ECO-Action whose mission is to help communities organize to confront environmental health threats, and to strengthen and facilitate participation of communities in preventing and resolving such threats. Mr. Noibi is also a member of the HERCULES Stakeholder Advisory Board.