About

Sean M. Harris, PhD, is a Research Assistant Professor in the Department of Environmental Health Sciences at the U-M School of Public Health. His research aims to advance understanding of how environmental toxicants contribute to adverse pregnancy outcomes such as preterm birth and preeclampsia. Dr. Harris employs a combination of approaches including transcriptomics, metabolomics, primary tissue models, and computational/data mining methods to investigate the molecular mechanisms of toxicant effects on the placenta and fetal membranes. He also investigates extracellular vesicles as a source for circulating biomarkers of toxicant effects on the placenta. His research projects include studying the impact of chlorinated hydrocarbons like trichloroethylene and perchloroethylene on the placenta, utilizing primary placenta tissue models and integrated omics approaches. Dr. Harris's work is part of larger programs such as the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) and the Michigan Center on Lifestage Environmental Exposures and Disease (M-LEEaD). His expertise encompasses female reproductive toxicology, immunotoxicology during pregnancy, toxicant-pathogen interactive effects in pregnancy, extracellular vesicle biology, and computational toxicology. Dr. Harris's contributions include investigating how environmental chemicals influence pregnancy-related genes and pathways, with a focus on identifying biomarkers and understanding molecular mechanisms underlying adverse pregnancy outcomes.

Research topics

• Biology
• Environmental science
• Bioinformatics
• Environmental chemistry
• Computational biology
• Organic chemistry
• Chemistry
• Genetics
• Medicine

Selected publications

• Identification of chemicals targeting dementia genes and pathways in the Comparative Toxicogenomics Database

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-12-22

  articleOpen access

  Abstract Introduction Dementia is a public health challenge and exposures likely contribute to risk, though many have not been evaluated. We screened chemicals for enrichment with dementia genes and related pathways. Methods We obtained gene lists from the Comparative Toxicogenomics Database for 1,008 chemicals and nine dementia-related pathways (e.g., Alzheimer’s disease, tauopathies). We tested pairwise chemical-dementia gene enrichment using Fisher’s exact tests and proportional reporting ratios (PRR), accounting for multiple comparisons with false discovery rate (FDR<1×10 - 6 ). Results Of the chemicals tested, 742 (73.6%) were enriched for at least one dementia pathway and 15 with all nine pathways, including benzo(a)pyrene, ethanol, paraquat, and particulate matter. We observed 295 chemicals enriched for Alzheimer’s disease, including sodium arsenite (PRR = 57.9) and 305 enriched for tauopathies, including bisphenol A (PRR=37.7). Discussion We identified chemicals enriched for dementia pathways, suggesting broad classes of chemicals contribute to dementia.

  PublisherDOI

• Current approaches and advances in placental toxicology

  Trends in Endocrinology and Metabolism · 2025-06-04 · 4 citations

  reviewOpen access
  PublisherOA PDFDOI

• Evaluating impacts of the trichloroethylene metabolite <i>S</i> -(1,2-dichlorovyinyl)-L-cysteine on transcriptomic responses and cytokine release in a macrophage model: implications for pregnancy outcomes

  Journal of Immunotoxicology · 2025-07-03 · 1 citations

  articleOpen accessSenior authorCorresponding

  cytokine suppression and determined that inhibition of cytokine release was the more potent endpoint compared to cytotoxicity. Finally, we analyzed a previously generated transcriptomic dataset from THP-1 cells stimulated with LPS, with or without DCVC treatment. We identified transcription factors that were enriched with DCVC and/or LPS treatment, including NF-kB and Vitamin D receptor (VDR). Our findings show that DCVC potently alters cellular and molecular macrophage immune responses involved in defense against intrauterine pathogens.

  PublisherDOI

• Novel high throughput screen reports that benzo(a)pyrene overrides mouse trophoblast stem cell multipotency, inducing SAPK activity, HAND1 and differentiated trophoblast giant cells

  Placenta · 2024-01-19 · 1 citations

  article
  PublisherDOI

• Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and their influence on inflammatory biomarkers in pregnancy: Findings from the LIFECODES cohort

  Environment International · 2024-11-13 · 16 citations

  articleOpen access

  BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are fluorinated chemicals linked to adverse pregnancy and birth outcomes. However, the underlying mechanisms, specifically their effects on maternal inflammatory processes, are not well characterized. OBJECTIVE: We examined associations between prenatal PFAS exposure and repeated measures of inflammatory biomarkers, including C-reactive protein (CRP) and four cytokines [Interleukin-10 (IL-10), IL-1β, IL-6, and tumor necrosis factor-α (TNF-α)]. METHODS: We analyzed data from 469 pregnant women in a nested case-control study of preterm birth at Brigham and Women's Hospital in Boston, Massachusetts (2006-2008). We measured nine PFAS in early pregnancy plasma samples (median gestation: 10 weeks), with inflammatory biomarkers measured at median gestations of 10, 18, 26, and 35 weeks. We used linear mixed models for repeated measures and multivariable regression for visit-specific analysis to examine associations between each PFAS and inflammation biomarker, adjusting for maternal demographics, pre-pregnancy BMI, and parity. We examined the effects of PFAS mixture using sum of all PFAS (∑PFAS) and quantile-based g-computation approaches. RESULTS: We observed consistent inverse associations between most PFAS and cytokines, specifically IL-10, IL-6, and TNF-α, in both single pollutant and mixture analyses. For example, an interquartile range increase in perfluorooctanesulfonic acid was associated with -10.87 (95% CI: -19.75, -0.99), -13.91 (95% CI: -24.11, -2.34), and -8.63 (95% CI: -14.51, -2.35) percent change in IL-10, IL-6, and TNF-α levels, respectively. Fetal sex, maternal race, and visit-specific analyses showed associations between most PFAS and cytokines were generally stronger in mid-pregnancy and among women who delivered males or identified as African American. CONCLUSIONS: The observed suppression of both regulatory (IL-10) and pro-inflammatory (TNF-α) cytokines suggests that PFAS may alter maternal inflammatory processes or immune functions during pregnancy. Further research is needed to understand the effects of both legacy and newer PFAS on inflammatory pathways and their broader clinical implications.

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• The antioxidant <i>N</i>‐acetyl cysteine inhibits cytokine and prostaglandin release in human fetal membranes stimulated ex vivo with lipoteichoic acid or live group B streptococcus

  American Journal of Reproductive Immunology · 2024-01-01 · 1 citations

  articleOpen accessCorresponding

  BACKGROUNDS: Infection during pregnancy is a significant public health concern due to the increased risk of adverse birth outcomes. Group B Streptococcus or Streptococcus agalactiae (GBS) stands out as a major bacterial cause of neonatal morbidity and mortality. We aimed to explore the involvement of reactive oxygen species (ROS) and oxidative stress pathways in pro-inflammatory responses within human fetal membrane tissue, the target tissue of acute bacterial chorioamnionitis. METHODS: We reanalyzed transcriptomic data from fetal membrane explants inoculated with GBS to assess the impact of GBS on oxidative stress and ROS genes/pathways. We conducted pathway enrichment analysis of transcriptomic data using the Database for Annotation, Visualization and Integrated Discovery (DAVID), a web-based functional annotation/pathway enrichment tool. Subsequently, we conducted ex vivo experiments to test the hypothesis that antioxidant treatment could inhibit pathogen-stimulated inflammatory responses in fetal membranes. RESULTS: ). There were 31 significantly changed genes associated with these pathways, most of which were upregulated after GBS inoculation. In ex vivo experiments with choriodecidual membrane explants, our study showed that co-treatment with N-acetylcysteine (NAC) effectively suppressed the release of pro-inflammatory cytokines (IL-6, IL-8, TNF-α) and prostaglandin PGE2, compared to GBS-treated explants (p < .05 compared to GBS-treated samples without NAC co-treatment). Furthermore, NAC treatment inhibited the release of cytokines and PGE2 stimulated by lipoteichoic acid (LTA) and lipopolysaccharide (LPS) in whole membrane explants (p < .05 compared to LTA or LPS-treated samples without NAC co-treatment). CONCLUSIONS: Our study sheds light on the potential roles of ROS in governing the innate immune response to GBS infection, offering insights for developing strategies to mitigate GBS-related adverse outcomes.

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• Interplay of education and DNA methylation age on cognitive impairment: insights from the Health and Retirement Study

  GeroScience · 2024-09-25 · 7 citations

  articleOpen access

  Few studies have assessed the association of educational attainment on dementia and cognitive impairment through DNA methylation age acceleration, while accommodating exposure-mediator interaction effects. We evaluated the mediation role of six epigenetic clocks with dementia, cognitive impairment non-dementia, and normal cognition, while accommodating exposure-mediator interaction effects. To understand the joint association of low education (≤12 years) and DNA methylation age acceleration (yes/no) in relation to cognitive impairment, we used weighted logistic regression, adjusting for chronological age, sex, race/ethnicity, and cell type composition. We performed four-way mediation and interaction decomposition analysis. Analyses were conducted on 2016 venous blood study participants from the Health and Retirement Study (N = 3724). Both GrimAge acceleration (OR = 1.6 95%CI 1.3-2.1) and low educational attainment (OR = 2.4 95%CI 1.9-3.0) were associated with higher odds of cognitive impairment in a mutually adjusted logistic model. We found additive interaction associations between low education and GrimAge acceleration on dementia. We observed that 6-8% of the association of education on dementia was mediated through GrimAge acceleration. While mediation effects were small, the portion of the association of education on dementia due to additive interaction with GrimAge acceleration was between 23.6 and 29.2%. These results support the interplay of social disadvantage and biological aging processes on impaired cognition.

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• Early pregnancy serum PFAS are associated with alterations in the maternal lipidome

  Environmental Research · 2024-10-18 · 6 citations

  articleOpen access
  PublisherOA PDFDOI

• Placental single cell transcriptomics: Opportunities for endocrine disrupting chemical toxicology

  Molecular and Cellular Endocrinology · 2023-09-09 · 10 citations

  articleOpen access
  PublisherOA PDFDOI

• Trichloroethylene Metabolite <i>S</i>-(1,2-Dichlorovinyl)-<scp>l</scp>-cysteine Stimulates Changes in Energy Metabolites and Amino Acids in the BeWo Human Placental Trophoblast Model during Syncytialization

  Chemical Research in Toxicology · 2023-05-10 · 1 citations

  articleOpen access

  -(1,2-dichlorovinyl)-l-cysteine (DCVC), modifies energy metabolism and amino acid abundance in HTR-8/SVneo extravillous trophoblasts. In the current study, we investigated DCVC-induced changes to energy metabolism and amino acids during forskolin-stimulated syncytialization in BeWo cells, a human villous trophoblastic cell line that models syncytialization in vitro. BeWo cells were exposed to forskolin at 100 μM for 48 h to stimulate syncytialization. During syncytialization, BeWo cells were also treated with DCVC at 0 (control), 10, or 20 μM. Following treatment, the targeted metabolomics platform, "Tricarboxylic Acid Plus", was used to identify changes in energy metabolism and amino acids. DCVC treatment during syncytialization decreased oleic acid, aspartate, proline, uridine diphosphate (UDP), UDP-d-glucose, uridine monophosphate, and cytidine monophosphate relative to forskolin-only treatment controls, but did not increase any measured metabolite. Notable changes stimulated by syncytialization in the absence of DCVC included increased adenosine monophosphate and guanosine monophosphate, as well as decreased aspartate and glutamate. Pathway analysis revealed multiple pathways in amino acid and sugar metabolisms that were altered with forskolin-stimulated syncytialization alone and DCVC treatment during syncytialization. Analysis of ratios of metabolites within the pathways revealed that DCVC exposure during syncytialization changed metabolite ratios in the same or different direction compared to syncytialization alone. Building off our oleic acid findings, we found that extracellular matrix metalloproteinase-2, which is downstream in oleic acid signaling, underwent the same changes as oleic acid. Together, the metabolic changes stimulated by DCVC treatment during syncytialization suggest changes in energy metabolism and amino acid abundance as potential mechanisms by which DCVC could impact syncytialization and pregnancy.

  PublisherOA PDFDOI

Recent grants

• Project 3 - Effect of Extreme Weather on Potential Exposure of Contaminant Mixtures in Karst Water Systems

  NIH · $13.7M · 2010–2026

Frequent coauthors

• Rita Loch‐Caruso

  University of Michigan–Ann Arbor

  21 shared

• Kelly M. Bakulski

  University of Michigan–Ann Arbor

  12 shared

• Elana R. Elkin

  San Diego State University

  12 shared

• Anthony L. Su

  Translational Therapeutics (United States)

  11 shared

• Erica Boldenow

  Calvin University

  7 shared

• Elizabeth E. Puscheck

  Wayne State University

  6 shared

• Daniel A. Rappolee

  Wayne State University

  6 shared

• Olivia Harlow

  Calvin University

  6 shared