Today is Tuesday, Mar. 26, 2019

Department of Environmental Health

Center for Environmental Genetics


Funded Projects

For a list of pilot projects funded through the CEG (NIEHS award P30 ES006096) between 2012 and 2018, click here.

The recipients of 2018 CEG pilot funds are as follows:

Innovator awards

Yuet-Kin (Ricky) Leung, PhD, for his study of exposure to the BPA replacement chemical bisphenol AF (BPAF) and its potential to influence prostate cancer development. Dr. Leung and his team hypothesize that prenatal BPAF exposure re-programs prostate stem cells during gestation and stimulates stem cell expansion in the epithelial and stromal compartments, via estrogen receptors, giving rise to prostate enlargement in adult offspring. Dr. Leung and his team will use CF1 mice to investigator the impact of in utero BPAF exposure on prostate stem cells and will determine the role of estrogen receptors in mediating the effects caused by such exposure in the same model.

Kyounghyun Kim, PhD, for his study of the mechanism by which polycyclic aromatic hydrocarbons (PAHs) may contribute to the development of breast cancer by inhibiting activity of the nuclear receptor NR2E3. Dr. Kim and his team will explore the mediating roles of the NR2E3 homodimer-Sp1 transcription factor complex and the phytochemical resveratrol, which is a component of red wine.  The study aims to identify a novel mechanism of gene-environment interactions in breast cancer development and to provide a scientific basis for novel preventive strategies by targeting NR2E3.

Bin Ouyang, MD, for his study of phthalate exposure and DNA methylation in firefighters. Prior work by Ouyang and colleagues identified that certain genes, including reproduction related hormone genes (TDRD6, PTCHD3, KLHL17 and PDIA2) were epigenetically modified in pooled firefighters blood samples. The team also found that in vitro treatment of phthalate inhibited blood cell line proliferation, induced DNA hypomethylation and upregulated KLHL17 gene expression. Thus, Ouyang and colleagues hypothesize that that long-term exposure to combustion toxicants such as phthalates can disrupt hormonal balance and impair reproductive system in firefighters through dysregulation of DNA methylation. The goal is to discover exposure-induced epigenetic DNA biomarkers for assessing
reproduction-related risk in firefighters facing chronic toxic substance exposure from firefighting

Affinity group awards

Aimin Chen, MD, PhD, for his team’s study of exposure to suspected endocrine disrupting chemicals including bisphenol F (BPF), bisphenol S (BPS), and replacement phthalates and phthalate alternatives (diisobutyl phthalate [DiBP], di-n-octyl phthalate [DnOP], diisononyl phthalate [DiNP]), and Benzophenone-3 (BP-3), a widely used ultraviolet filter found in sunscreen. Chen and colleagues will quantify exposures to these emerging EDCs in 80 pregnant women at delivery, via investigation of DNA methylation changes in the fetal side of the placenta and cord blood mononuclear cells (CBMCs) and will examine the associations with pregnancy outcomes such as gestational age and birth weight z score. It is anticipated that data gathered from this pilot project will contributed to a larger R01 type study to investigate the developmental toxicity of these emerging endocrine disrupting compounds.

Shuk-Mei Ho, PhD, for her team’s investigation of whether and how bisphenol S (BPS), a BPA replacement chemical, may induce oxidative stress and DNA damage and reduce the viability and motility of human sperm. Based on chemical similarity between BPA and BPS, Ho and colleagues hypothesize that BPS increases oxidative stress (OS)-related DNA damage and induces region- and/or CpG-specific aberrant DNA methylation, leading to impaired sperm function. The team seeks to illuminate for the first time mechanisms underlying low-dose BPS/BPA effects on sperm functions, identify potential epigenetic biomarkers that may help assess poor sperm quality associated with environmental exposure, and contribute to evidence-based solutions for male infertility.

Jagjit Yadav, PhD, for his team’s efforts to develop a 3-dimensional in vitro air-liquid interface (ALI) co-culture model to better understand the impact of carbon nanotube (CNT) exposure on chronic lung pathology, including prolonged inflammation, airway remodeling and fibrotic responses. Specifically, Dr. Yadav and colleagues seek to develop an alveolar 3D-organotypic culture model based on effector/target (AT2/AM) cell co-cultures. If successful, the work will generate new knowledge of cell-specific mechanisms and paradigm-shifting tools for designing mechanistically relevant alternative toxicity screening platforms for early risk assessment. This, in turn, could lead to intervention strategies that would help decide future CNT design and production criteria and avert exposure risks.   

Shouxiong Huang, PhD, for his team's investigation of single cell transcriptomics to reveal cellular and molecular targets of PPARγ regulation in PAH-exposed placenta.Polycyclic aromatic hydrocarbons (PAHs) have been associated with multiple pregnancy disorders in humans. A balanced pro- and anti-inflammatory response orchestrated by various immune cell subsets in placenta plays a critical role for pathogenesis and outcome of pregnancy disorders. This study is focused on investigating the interaction between pollutant BaP-altered and PPARγ-mediated gene networks, which will be revealed by single cell transcriptomes. Novel findings will be further developed to an R01 proposal to discover targets, biomarkers, and intervention in air pollutant-exacerbated pregnancy disorders.

Maria F. Czyzyk-Krzeska, MD, PhD, for her team's exploration of the role of heavy metals speciation in clear cell renal cell carcinoma (ccRcc).  Exposures to heavy metals -- in particular cadmium (Cd), arsenic (As), and lead (pB) are established environmental and occupational risk factors in renal cancel.  This project seeks to examine the molecular distribution of metals, and its role versus total content, as the driving force for the carcinogenic effects of toxic metals. 

New Investigator Awards

Kelly Brunst, PhD, for what is described as the first study to use an epigenome-wide approach to explore the role of DNA methylation mechanisms linking exposure to traffic-related air pollution (TRAP) and alterations in brain metabolism among adolescents. Specifically, Dr. Brunst and her collaborators will use neuroimaging paired with magnetic resonance spectroscopy (MRS) to non-invasively measure levels of brain metabolites in vivo among brain regions important for executive functioning, regulating emotional processing, and implicated in the neurobiology of mental health disorders.

Katherine Burns, PhD, for her investigation of the impact of chronic DEHP [Bis(2-ethylhexyl) phthalate] exposure in women susceptible to endometriosis and whether such exposure tilts the IL6-signaling balance towards IL6 trans-signaling, in turn leading to a chronic inflammatory environment. Previous work by Burns found the initiation of endometriosis to be immune-dependent, and changing interleukin 6 (IL6)-signaling affects lesion numbers. Disease progression is reliant on cytokine signaling and infiltration of innate immune cells. IL6 is a secreted cytokine from uterine epithelial cells and PMNs and signals via classical- and trans-signaling pathways. Burns and her staff seek to identify the dose response of DEHP that increases the incidence of endometriosis and identify how DEHP alters signaling through IL6. In so doing, they seek to generate insights toward the larger goals of identifying diagnostic targets and improving prevention of a disease that affects more than 7 million American women and adolescents.