What We Do

One of the most difficult challenges for environmental health assessment is to evaluate hazards from exposure to chemical mixtures. PAHs exist in the environment as mixtures. The toxicity of individual PAHs can change depending on the other PAHs in that mixture. Therefore, our project is looking to understand how individual PAHs contribute to the overall toxicity of a mixture. We use an in vitro 3D human lung model to look at the relationship between the chemicals in a mixture and their toxicity. This human lung model is composed of primary human bronchial epithelial cells and mimics a human airway. The results of these studies will be used to assess the toxicity of mixtures from Superfund sites and determine the risk they pose to human health.

Our project asks the following questions

What is the role of metabolism in susceptibility for PAH-mediated toxicity and respiratory disease in humans?

PAHs can be metabolized in the human body, forming new chemicals (metabolites). We will use our 3D lung model to determine the extent of PAH metabolism in bronchial epithelial cells. This model provides a unique opportunity to study the role of metabolism and how that may impact the toxicity of PAHs in the body.

Can we predict toxicity and disease phenotype on the basis of biomarkers and pathways that are altered after PAH exposure?

We are very interested in learning how individual PAHs contribute to the overall toxicity of a mixture. We are looking at different components of a mixture, to learn how to predict the toxicity of new mixtures. To do this, we have created several sufficiently similar mixtures from environmental data. Supermix10 is one example of these mixtures. We can then look at the different chemicals in this mixture, which represents environmental data from the Portland Harbor Superfund Site, to determine which chemicals are driving the toxicity of the mixture.

Can current remediation techniques reduce human health hazards?

As Superfund Sites are remediated, there is concern that these techniques may unfortunately increase toxicity by altering PAHs to other chemicals. Therefore, we will test PAH mixtures before and after remediation for toxicity in our 3D lung model.

Do common genetic polymorphisms alter toxicity and subsequent risk to PAH exposure and thereby allow us to identify susceptible individuals?

We are interested in understanding the risk PAHs pose to human health. Certain individuals may be more at risk for adverse health outcomes after inhalation exposure to PAHs given their genetic profile. There are common polymorphisms to the enzymes responsible for metabolizing PAHs (CYP1B1 and GSTM1). We are looking to see if having these polymorphisms makes an individual more susceptible to PAH toxicity.

Our Current Research

  • Elucidating the mechanisms of PAH toxicity in the 3D human lung model.
  • Quantifying the toxicity of individual PAHs and PAH mixtures in the 3D human lung model.
  • Determining whether individual PAHs contribute to the toxicity of PAH mixtures in an additive manner.
  • Assessing the role of metabolism on the toxicity of individual PAHs in the 3D human lung model.
  • Measuring uptake and metabolism of biologically active PAHs in 3D human lung model.