Project Title:  Metabolomic effects of folic acid supplementation and unmetabolized folic acid (FA) in a randomized, double-blind, placebo controlled FA trial
Principal Investigator:  Mary Gamble, PhD, Associate Professor of Environmental Health Sciences
Co-Investigators: Ana Navas-Acien, MD, PhD, Professor of EHS; Terry Bottiglieri, PhD, Program Director of the Metabolomics Center, Baylor Research Institute, Dallas, TX; Michael Reed, PhD, Professor of Mathematics, Duke University; H. Frederik Nijhout, PhD, Professor of Biology, Duke University
Year:  2018-2019
Award Amount: $33,000

Abstract:  Food fortification with folic acid (FA) is mandated in 87 countries. FA, is a synthetic inactive form of folate that is more stable than 5mTHF, the natural form in foods. People vary in their ability to metabolize FA to 5mTHF. Unmetabolized FA (UMFA) in serum is present in >95% of NHANES participants. This widespread exposure has stirred critical questions regarding unanticipated effects. Recently, an expert panel convened by the NIEHS National Toxicology Program systematically reviewed the safety and toxicity of high FA, concluding that there is uncertainty and there is a critical need to identify potential indices of metabolic dysfunction associated with UMFA or high FA intake. It is virtually impossible to address this in the US because exposure to FA is universal and UMFA in serum is pervasive. The primary goal of this proposal is to leverage samples from a recently completed randomized, controlled trial (RCT) of FA supplementation in Bangladesh – a FA-naïve population – to use metabolomics to identify novel metabolites and pathways altered by FA supplementation (Aim 1) and UMFA (Aim 2) in a new collaboration with Dr. Bottiglieri, Director of the Metabolomics Center at Baylor. We wish to conduct pilot studies to demonstrate feasibility for an R01 that will ultimately use discovery-, validation- and dose-dependent approaches to test the hypotheses that FA supplementation and/or UMFA influence previously unknown downstream metabolites and pathways, and link these exposures to potential downstream health outcomes. The findings of this study may inform policy decisions regarding FA fortification programs, public health recommendations, e.g. for neural tube defect prevention, and the forms and doses of folate sold in over-the-counter supplements.

Project Title: 
The Influence of Light Pollution and Light-at-night on the Circadian Clock
Principal Investigators: Micaela Martinez-Bakker, PhD, Assistant Professor of Environmental Health Sciences
Co-Investigator:  Barbara Helm, PhD, University of Glasgow, Scotland, UK
Year:  2018-2019
Award Amount: $30,000

Abstract:  The human circadian clock, a powerful regulator of health, is entrained by light. We aim to quantify the mismatch between natural light cycles and those experienced by children and adults to determine if/how this mismatch impacts the circadian clock and a disease with a circadian influence (asthma). In modern society, humans live within Realized Light Cycles (RLCs) that are generated by the intersection of (i) natural light cycles (ii) indoor light use (e.g., room lighting and electronics), and (iii) outdoor light pollution. We will characterize RLCs people experience in their day-to-day life and the degree to which light pollution and indoor light use contributes to the mismatch between RLCs and natural light cycles. We will also test if RLCs are seasonally modulated by changes in photoperiod, or if people live in perpetual summer light. To test whether physiology covaries with RLCs, we will use body temperature as a non-invasive readout of the circadian clock. We predict that the circadian clock is phase-shifted by light pollution and indoor light at night. This research could inform the regulation of light pollution, and inspire new technology to minimize circadian disruption and its downstream health effects. Importantly, we also predict that circadian disruption caused by light at night could have a modifying effect on disease by altering circadian rhythms in immune cell trafficking and the inflammatory response. We will, therefore, explore these relationships by studying asthma in the context of circadian disruption.

Project Title:  Nuisance Flooding, Exposure Pathways and Stress in a Population Surrounding Jamaica Bay, New York
Principal Investigators: Pam Factor-Litvak, PhD, Professor of Epidemiology
Co-Investigator:  Andrew Juhl, PhD, Associate Research Professor at Lamont and Beizhan Yan, PhD, Associate Research Professor at Lamont.
Year:  2018-2019
Award Amount: $30,000

Abstract: Marine environments near cities often suffer from poor water quality because of legacy contaminants and ongoing pollution. The health impacts from contaminants in urban waters are likely to increase when coastal flooding carries those contaminants back onshore and deposits them into urban landscapes, expanding the possible routes of exposure, and the number of people potentially exposed. Supporting evidence comes primarily from increased contaminant levels in areas that flooded during major storms. For example, high levels of fecal indicator bacteria and several heavy metals, including mercury, were found in sediments and debris left in New York City neighborhoods following Hurricane Sandy. In addition to such large events, which occur infrequently (> once per decade), many NYC neighborhoods are also impacted by minor storms and tides (i.e. nuisance events), though little is known about the environmental and health impacts of nuisance floods. Although the area and number of individuals that could be impacted per event is smaller, the high frequency of such events may lead to significant cumulative impacts. Furthermore, both extreme events and nuisance flooding are predicted to increase in frequency due to ongoing climate change, suggesting that concerns about onshore transport of contaminated marine water and sediments are likely to expand. Assessing the health risks of onshore contaminant transport is hampered by fundamental knowledge gaps related to how different contaminants are mobilized and deposited across the range of coastal flooding severity and frequency, differences in the environmental persistence of various contaminants, the relative importance of secondary effects, such as growth of mold in flooded homes, whether elevated contaminant levels in the environment translate to human exposures, and how flooding-related exposure and psychological stress relate to each other. The proposed project is a highly interdisciplinary, multi-level translational study linking local water and underwater sediment quality with onshore contamination levels along gradients of flooding frequency within the area of Jamaica Bay, New York. We will measure levels of flood-borne contaminants in outdoor soils, link them to levels in the indoor environment, and finally to measures of objective and subjective stress (hair cortisol and questionnaire based measures). We focus environmental and human measurements on contaminants with well-known health outcomes that are associated with the waters and underwater sediments of the NYC area, including: sewage-derived pathogens, mercury, other heavy metals, pharmaceuticals and polychlorinated biphenyls (PCBs). This pilot project will provide unique preliminary information regarding environmental and human sequelae to frequent coastal inundations and provide preliminary data to support an Oceans, Climate and Health Center proposal, should the RFA be reissued; if not, a R01 to be submitted in Summer 2018.

Project Title:  Evaluation of genomic instability in pesticide-exposed B cells
Principal Investigator: Rebecca Leeman-Neill, MD, PhD, Assistant Professor of Pathology and Cell Biology
Year:  2018-19
Award Amount:  $35,000

Abstract:  Epidemiologic studies have demonstrated associations between pesticide exposures and lymphoma risk. The overarching goal of this proposal is to clarify the causal link between pesticide exposures and lymphoma. Key genetic events driving lymphoma rely on the enzyme activation-induced cytidine deaminase (AID), a mutagenic enzyme known to be responsible for chromosomal translocations and mutations that drive B cell lymphomas. In preliminary studies, B cell exposure to commonly used phenylurea herbicides induced AID expression. The aims of the proposed study are to evaluate the effects of pesticides on AID-dependent and independent genomic instability in B cells a) in vitro and b) in vivo. The link between pesticide exposures and B cell genomic instability, including the possible role of AID, will be investigated through the use of a high throughput translocation sequencing methodology that sensitively detects evidence of DNA damage. Results will be compared in wild type cellular and mouse models compared to those in which AID has been deleted. The results will lay the groundwork for future work examining the lymphomagenic potential of AID-inducing chemicals and the mechanistic link between pesticide exposures and AID. Identification of the biological mechanisms underlying pesticide-related lymphomagenesis will impact environmental health by guiding pesticide use, identifying at-risk populations, and preventing lymphoma.

Project Title:  Household Dust Microbiome and Idiopathic Pulmonary Fibrosis
Principal Investigator:  Anna Podolanczuk, MD, MS, Assistant Professor of Medicine, Division of Pulmonary, Allergy and Critical Care
Co-Investigators: Matt Perzanowski, PhD, Associate Professor of EHS; Anne-Catrin Uhlemann, MD, PhD, Associate Professor of Medicine, Division of Infectious Diseases; David Lederer, MD, MS, Associate Professor of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine
Year:  2018-19
Award Amount:  $35,000

Abstract:  Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease with no cure affecting 1 in 200 older adults, with a median survival of only 3.8 years. IPF shares genetic, clinical, radiologic, and pathologic features with chronic hypersensitivity pneumonitis (HP), an interstitial lung disease (ILD) characterized by inflammation and/or fibrosis of the pulmonary parenchyma and small airways. Environmental exposure to mold and other inhaled antigens is a defining feature of HP. Since many patients with fibrotic ILD present with features of both IPF and chronic HP on histology and by high-resolution CT imaging, our conceptual model has evolved into one that places IPF and chronic HP on opposite ends of a spectrum. If true, then home fungal and bacterial exposures, known to cause chronic HP, may also be novel (and targetable) risk factors for IPF. We propose to conduct a case-control study of IPF cases, chronic HP cases, and heart failure controls to test whether household fungal and bacterial exposure is associated with biopsy-proven IPF. Study staff will perform home visits to collect household dust. Fungal and bacterial taxa in dust samples will be identified using next-generation sequencing. Serologic evidence of sensitization to identified microbes will be measured by immunoassays. This study will serve as groundwork for R01 applications that focus on gene-environment interactions in IPF and on immune mechanisms that mediate host-environment interactions in IPF.

Project Title:  Assessment of Mercury and Other Metals in Biospecimens from the Strong Heart Family Study
Principal Investigators: Ana Navas-Acien, MD, PhD, Professor of Environmental Health Sciences and Anne Nigra, EHS Doctoral Student
Co-Investigators: Marcia O’Leary and Joe Yracheta, Missouri Breaks Industries Research Inc. (MBIRI), Eagle Butte, SD
Year:  2018-2019
Award Amount: $23,000

Abstract:  Research in The Strong Heart Study (SHS), a major population-based cohort of cardiovascular disease (CVD) and related risk factors in American Indians (AIs) living in communities in Arizona, North/South Dakota, and Oklahoma, has established that AIs have elevated exposure to arsenic, cadmium, uranium, and other toxic metals. CVD and diabetes are epidemic in AI communities, and data from our parent study (R01HL090863) determined that arsenic and cadmium exposure are important risk factors for incident CVD in the SHS. Community members and researchers from a SHS center in South Dakota are concerned about elevated inorganic and elemental mercury (Hg) exposure from nearby coal-fired power plants. Prior limited environmental Hg monitoring in air and soil supports exposure might be elevated. The proposed study will measure total Hg in blood and urine samples from a random-stratified sample of 150 participants in the Strong Heart Family Study (SHFS), an ongoing family-based extension of the original SHS cohort. Data resulting from this pilot study will be used as preliminary data in future R01 grants to evaluate Hg exposure and its health consequences in the SHS and SHFS cohorts. Because this population has low seafood intake, this is an ideal setting to study the health implications, including cardiovascular, immune and neurological effects, of coal-fired power plant-related Hg exposure, a major concern for many communities around the US and worldwide.