Faculty Bibliography

Wood is a type of biomass commonly burnt as a means of energy. When burnt, it releases harmful components linked to adverse health outcomes. In the scientific community toxicologists and epidemiologists continue to consider the individual components of woodsmoke "” such as particulate matter and polycyclic aromatic hydrocarbons "” as a way to better understand the relationship between inhaled woodsmoke and acute and chronic disease. In recent years, research focus has shifted toward the underlying mechanisms that could be associated with long-term health consequences. Alongside this research, novel studies in molecular toxicology that examine the impacts of woodsmoke could provide a link between woodsmoke and telomere length. Such studies could provide scientists with a better understanding on how woodsmoke leads to chronic diseases. As researchers from various disciplines come together to work on this complex and widespread issue, hope emerges to reduce the morbidity and mortality associated with this global air pollutant.

BACKGROUND:Economic and social marginalization among American Indians and Alaska Natives (AI/ANs) results in higher chronic disease prevalence. Potential causal associations between toxic environmental exposures and adverse health outcomes within AI/AN communities are not well understood. OBJECTIVES/OBJECTIVE:This review examines epidemiological literature on exposure to toxicants and associated adverse health outcomes among AI/AN populations. METHODS:PubMed, Embase, Cochrane, Environment Complete, Web of Science Plus, DART, and ToxLine were searched for English-language articles. The following data were extracted: lead author's last name, publication year, cohort name, study location, AI/AN tribe, study initiation and conclusion, sample size, primary characteristic, environmental exposure, health outcomes, risk estimates, and covariates. RESULTS:About 31 articles on three types of environmental exposures met inclusion criteria: persistent organic pollutants (POPs), heavy metals, and open dumpsites. Of these, 17 addressed exposure to POPs, 10 heavy metal exposure, 2 exposure to both POPs and heavy metals, and 2 exposure to open dumpsites. Studies on the Mohawk Nation at Akwesasne; Yupik on St. Lawrence Island, Alaska; Navajo Nation; Gila River Indian Community; Cheyenne River Sioux; 197 Alaska Native villages; and 13 tribes in Arizona, Oklahoma, North Dakota, and South Dakota that participated in the Strong Heart Study support associations between toxicant exposure and various chronic conditions including cardiovascular conditions, reproductive abnormalities, cancer, autoimmune disorders, neurological deficits, and diabetes. DISCUSSION/CONCLUSIONS:The complex interplay of environmental and social factors in disease etiology among AI/ANs is a product of externally imposed environmental exposures, systemic discrimination, and modifiable risk behaviors. The connection between environmental health disparities and adverse health outcomes indicates a need for further study.

Background: Studies have revealed the increased incidence of health disorders in First Responders (FR) who were at Ground Zero over the initial 72 hr after the World Trade Center (WTC) collapses. Previous studies in rats exposed to WTC dusts using exposure scenarios that mimicked FR mouthbreathing showed exposure led to altered expression of genes whose products could be involved in lung ailments. Nevertheless, it was uncertain if repeated exposures (as occurred in earliest days post-disaster) might have given rise to long-term changes in the lungs/other organs, in white blood cell (WBC) profiles, and/or systemic expression of select (mostly immune-related) proteins.Methods: To examine this, rats were exposed on 2 consecutive days (2 hr/d, intratracheal inhalation) to WTC dusts and then examined over a 1-yr period thereafter. At select times post-exposure, organ (lung, heart, liver, kidney, spleen) weights, WBC profiles, and blood levels of a variety of proteins were evaluated.Results: The study showed that over the 1-yr period, there were nominal effects on organ weights (absolute, index) as a result of the dust exposures. There were significant changes (relative to in naïve rats) in WBC profiles, with exposed rats having increased monocyte-macrophage and decreased lymphocyte percentages. The study also found that dust exposure led to significant systemic increases in many proteins, including MCP-1, RANTES, MMP-9, RAGE, and Galectin-3.Conclusions: These results provide further support for our longstanding hypothesis that the WTC dusts could potentially have acted as direct inducers of many of the health effects that have been seen in the exposed FR.

BACKGROUND:In an effort to decrease the rates of smoking conventional tobacco cigarettes, electronic cigarettes (e-cigarettes) have been proposed as an effective smoking cessation tool. However, little is known about their toxicological impacts. This is concerning given that e-cigarette use is perceived as less harmful than conventional tobacco cigarettes during pregnancy for both the mother and fetus. OBJECTIVE:The goal of this study was to test the neurodevelopmental consequences of maternal e-cigarette use on adult offspring behavior and neuroimmune outcomes. METHODS: RESULTS: DISCUSSION/CONCLUSIONS:These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.

It appears that electronic cigarettes (EC) are a less harmful alternative to conventional cigarette (CC) smoking, as they generate substantially lower levels of harmful carcinogens and other toxic compounds. Thus, switching from CC to EC may be beneficial for smokers. However, recent accounts of EC- or vaping-associated lung injury (EVALI) has raised concerns regarding their adverse health effects. Additionally, the increasing popularity of EC among vulnerable populations, such as adolescents and pregnant women, calls for further EC safety evaluation. In this state-of-the-art review, we provide an update on recent findings regarding the neurological effects induced by EC exposure. Moreover, we discuss possible neurotoxic effects of nicotine and numerous other chemicals which are inherent both to e-liquids and EC aerosols. We conclude that in recognizing pertinent issues associated with EC usage, both government and scientific researchers must address this public health issue with utmost urgency.

World Trade Center (WTC) responders were exposed to mixture of dust, smoke, chemicals and carcinogens. New York University (NYU) and Mount Sinai have recreated WTC exposure in rodents to observe the resulting systemic and local biological responses. These experiments aid in the interpretation of epidemiological observations and are useful for understanding the carcinogenesis process in the exposed human WTC cohort. Here we describe the implementation of a tissue bank system for the rodents experimentally exposed to WTC dust. NYU samples were experimentally exposed to WTC dust via intratracheal inhalation that mimicked conditions in the immediate aftermath of the disaster. Tissue from Mount Sinai was derived from genetically modified mice exposed to WTC dust via nasal instillation. All processed tissues include annotations of the experimental design, WTC dust concentration/dose, exposure route and duration, genetic background of the rodent, and method of tissue isolation/storage. A biobank of tissue from rodents exposed to WTC dust has been compiled representing an important resource for the scientific community. The biobank remains available as a scientific resource for future research through established mechanisms for samples request and utilization. Studies using the WTC tissue bank would benefit from confirming their findings in corresponding tissues from organs of animals experimentally exposed to WTC dust. Studies on rodent tissues will advance the understanding of the biology of the tumors developed by WTC responders and ultimately impact the modalities of treatment, and the probability of success and survival of WTC cancer patients.

Numerous epidemiological and animal studies have demonstrated that exposure to ambient fine particulate matter (<2.5mum in diameter [PM2.5]) during gestation is associated with adverse obstetric outcomes including preterm birth (PTB). Early delivery has been linked to several lifetime health consequences for offspring, including behavioral and psychological abnormalities and reduced immune and respiratory functions. In a previous study performed in this laboratory, B6C3F1 pregnant mice exposed to concentrated ambient PM (CAPs) by inhalation, demonstrated shortened (by 0.4 d) gestational duration compared to filtered air (FA) controls. The mechanisms underlying the association between PM2.5 and PTB are not currently well understood. Since the placenta provides a crucial link between the intrauterine environment and fetal growth/development, it is a major target of PM and key for studying the effects on birth outcomes. Therefore, in this study, placentae from the previously developed pregnant mouse model (n=6 each from CAPs and FA groups) were subjected to whole transcriptomic profiling by RNAseq. A bioinformatic RNAseq analysis workflow (tximport, Salmon and edgeR /limmavoom) was used to identify differentially expressed genes between treatment groups. The 648 genes from the curated dbPTB (database Preterm Birth) were used for a candidate gene approach and were examined using gene counts obtained from RNAseq. Following PM2.5 exposure, six PTB genes were downregulated in placentae (Ace, Ddah1, Col1a2, Chst15, Akap12, Ephx1) and one was upregulated (Chys3) (p<0.01). Gene Ontology demonstrated that these seven genes are involved in neutrophil-mediated immunity, arterial blood pressure regulation, amino acid binding, cell membrane function, metal ion binding, and aromatic compound catabolism among other functions that could be linked to PTB. Additional computational models, agnostically testing placenta transcriptome-wide differential gene expression, revealed additional genes that were differentially expressed between the two treatment groups. These findings suggest that PM exposure influences the placenta genome thereby mediating PTB. Identification of these differentially expressed genes may contribute to intervention strategies to mitigate these adverse effects

An excess incidence of prostate cancer has been identified among World Trade Center (WTC) responders. In this study, we hypothesized that WTC dust, which contained carcinogens and tumor-promoting agents, could facilitate prostate cancer development by inducing DNA damage, promoting cell proliferation, and causing chronic inflammation. We compared expression of immunologic and inflammatory genes using a NanoString assay on archived prostate tumors from WTC Health Program (WTCHP) patients and non-WTC patients with prostate cancer. Furthermore, to assess immediate and delayed responses of prostate tissue to acute WTC dust exposure via intratracheal inhalation, we performed RNA-seq on the prostate of normal rats that were exposed to moderate to high doses of WTC dust. WTC prostate cancer cases showed significant upregulation of genes involved in DNA damage and G₂-M arrest. Cell-type enrichment analysis showed that Th17 cells, a subset of proinflammatory Th cells, were specifically upregulated in WTC patients. In rats exposed to WTC dust, we observed upregulation of gene transcripts of cell types involved in both adaptive immune response (dendritic cells and B cells) and inflammatory response (Th17 cells) in the prostate. Unexpectedly, genes in the cholesterol biosynthesis pathway were also significantly upregulated 30 days after acute dust exposure. Our results suggest that respiratory exposure to WTC dust can induce inflammatory and immune responses in prostate tissue.Implications: WTC-related prostate cancer displayed a distinct gene expression pattern that could be the result of exposure to specific carcinogens. Our data warrant further epidemiologic and cellular mechanistic studies to better understand the consequences of WTC dust exposure.Visual Overview: http://mcr.aacrjournals.org/content/early/2019/06/18/1541-7786.MCR-19-0115/F1.large.jpg.

Following a 1983 chromic acid (hexavalent chromium [CrVI]) spill from a Garfield, NJ electroplating plant, CrVI-contaminated water was found in a local firehouse basement in 1993. An ATSDR public health advisory was issued for the plant site in 2010, and from 2008-2015, fourteen residential properties have required remediation to address CrVI-contaminated dust in the basements. As part of the Community Outreach and Engagement Core of the NYU NIEHS Center, seventytwo Garfield residents aged 18-65 years, participated in a community survey with the goal of identifying concerns related to environmental and community health. Thirty-two percent responded that they 'didn't know' if they were exposed to chemicals or pollutants where they live. This finding suggests a limited awareness of environmental chemical exposures, chromium contamination and/or potential exposure to CrVI. Furthermore, toenail clippings were collected from forty-seven Garfield residents and analyzed for total chromium levels to assess potential long-term exposure. On average, residents living on/inside the contaminated plume area had higher total chromium levels in their toenail clippings than residents living outside the plume area. However, chromium levels for all participants were within the range of historical normal. This study highlights the value of partnerships between environmentally-impacted community's and academic scientists working together to identify potential contaminant exposures and address public health concerns through research and environmental health education.

Accumulating evidence indicates the developing central nervous system (CNS) is a target of air pollution toxicity. Epidemiological reports increasingly demonstrate that exposure to the particulate matter (PM) fraction of air pollution during neurodevelopment is associated with an increased risk of neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD). These observations are supported by animal studies demonstrating prenatal exposure to concentrated ambient PM induces neuropathologies characteristic of ASD, including ventriculomegaly and aberrant corpus callosum (CC) myelination. Given the role of the CC and cerebellum in ASD etiology, this study tested whether prenatal exposure to concentrated ambient particles (CAPs) produced pathological features in offspring CC and cerebella consistent with ASD. Analysis of cerebellar myelin density revealed male-specific hypermyelination in CAPs-exposed offspring at postnatal days (PNDs) 11-15 without alteration of cerebellar area. Atomic absorption spectroscopy (AAS) revealed elevated iron (Fe) in the cerebellum of CAPs-exposed female offspring at PNDs 11-15, which connects with previously observed elevated Fe in the female CC. The presence of Fe inclusions, along with aluminum (Al) and silicon (Si) inclusions, were confirmed at nanoscale resolution in the CC along with ultrastructural myelin sheath damage. Furthermore, RNAseq and gene ontology (GO) enrichment analyses revealed cerebellar gene expression was significantly affected by sex and prenatal CAPs exposure with significant enrichment in inflammation and transmembrane transport processes that could underlie observed myelin and metal pathologies. Overall, this study highlights the ability of PM exposure to disrupt myelinogenesis and elucidates novel molecular targets of PM-induced developmental neurotoxicity.