Spring 2014 – GoMRI Researcher Interview with Dr. Demetri Spyropoulos and Lexi Temkin

Alexis Temkin, Ph.D. candidate at the Medical University of South Carolina, gets up close and personal during an alligator release trip. Image Credit: Jessica Cloy-McCoy, RFP-II: Using Embryonic Stem Cell Fate to Determine Potential Adverse Effects of Petroleum/ Dispersant Exposure.

Alexis Temkin, Ph.D. candidate at the Medical University of South Carolina, gets up close and personal during an alligator release trip. Image Credit: Jessica Cloy-McCoy, RFP-II: Using Embryonic Stem Cell Fate to Determine Potential Adverse Effects of Petroleum/ Dispersant Exposure.

(From Spring 2014 Newsletter) RFP-II: Using Embryonic Stem Cell Fate to Determine Potential Adverse Effects of Petroleum/Dispersant Exposure.

1. Tell us a bit about your research. What are the goals of your project?

Our goals are to assess potential long-term, even multigenerational, effects of crude oil and dispersant (e.g. COREXIT) as they relate to disease development in humans. Our lab uses stem cells as a surrogate for fetal growth to assess potential downstream, life-long effects of in utero exposures. We are focusing on how exposure to crude oil fractions, COREXIT components and/or mixtures could impact obesity and a variety of common disorders (e.g. metabolic, cancer, inflammation/immunity, cardiovascular and neurological).

2. What is your background and how did you get involved with this kind of work?

Lexi: I’m currently a Ph.D. candidate working with Demetri Spyropoulos at the Medical University of South Carolina. Before coming to MUSC I did my undergraduate degree in Biology and Dance at Connecticut College. After graduating college, I worked as a research technician studying DNA methylation at the Institute for Cancer Genetics at Columbia University, which is a way to measure environmental impacts on cellular activities. I’ve always been passionate about environmental health, personally and scientifically, so the Marine Biomedicine Program at MUSC and specifically Demetri’s research on crude oil and COREXIT as potential endocrine disruptors was a natural fit for me. Demetri’s background was in animal viruses (like the ones we use to make stem cells), developmental biology and stem/cancer cell research.

3. What are some of the most significant or exciting findings so far in your work?

Lexi: I think our most exciting results so far come from our work on engineered cells used as sensors for fat-inducing factors (so-called “ligand binding assays”). In these experiments we are looking for fractions of oil, COREXIT, or oil/COREXIT mixtures that activate molecular switches in circuits known to be responsible for regulating fat cell differentiation. Current results indicate that oil/COREXIT mixtures as well as COREXIT alone activate these receptors, potentially resulting in an obesogenic response (or promoting fat cell differentiation and obesity) due to exposure. We are now testing individual components of COREXIT to see if we can identify compounds that are responsible for receptor activation and one in particular has been identified (Manuscript in preparation). If we can identify the “toxic” component, this could potentially help guide dispersant development in the future by eliminating or substituting these harmful chemicals.

4. Can you tell us about what some of the broader implications of this work are, in terms of public health?

Demetri: In terms of public health, this work will have many implications. Firstly, we hope to be part of a fundamental change in the current school of thought: from one in which  a toxic compound is something that kills you or subsets of cells in you in  a relatively rapid fashion to one in which a toxic compound changes the way cells and tissues in the body behave, impacting overall immunological, neurological, cardiovascular, reproductive and/or cancer-free health. People often ignore warnings about risky lifestyle choices (e.g. smoking) but may be more responsive if they knew that these choices could hurt their children.

5. The impact of oil spills on public health is one of the five research themes that GoMRI has identified. In your opinion, what are some of the most important issues related to oil spills and public health? What are some of the research gaps in this area?

Lexi: I think the most important issues related to oil spills/dispersants and public health are seafood contamination and exposure assessments, especially regarding developing adequate methods for testing.

Demetri: We are just at the beginning of identifying components of oil/dispersant that may have long-term impacts on human health. Translating that into seafood contaminant and human exposure testing is a big step. We tend to think that a certain compound in oil or dispersant will accumulate in exposed individuals, with a certain concentration of it signifying a dangerous level. More likely, that compound will be metabolized in the body, affecting various processes, with persistent exposure leading to permanent changes in the body’s processes. It’s further complicated by the likelihood that the level at which that compound becomes dangerous is lower than we think, because of other compounds in the environment having additive effects. Before you feel too hopeless, we do have good clues to all of these, but as with any good detective novel, it will not be easy or straightforward.

6. Do you see areas in which public health and other scientific disciplines can integrate?

Lexi: Sure! There are certainly research gaps but I also think there is a communication gap between researchers, epidemiologists and the public. I think making sure the public understands research questions, the importance and reasoning behind them, as well as the impacts of the results, will greatly improve public health and general well being.

Demetri: On a practical level, individuals living in regions impacted by the Gulf oil spill should have regular physicals performed, including standard methods currently applied to blood and urine samples. Any trends in physical health or blood/urine chemistry indicating poorer health (relative to national and other regional statistics) should be of special interest. This would especially be useful in subsistence fishing communities where the link between potentially exposed seafood and humans is greatest.

7. As a member of the GoMRI community, what would you like to see this program accomplish over 10 years?

Lexi: I would really like to see more collaboration between industry, the medical community and academia. GoMRI is a unique group of scientists because the members and study questions cover a broad range of disciplines driven by different factors. It is evident that this collaboration is producing incredibly strong data sets. Hopefully the sense of community, support, and collaboration will continue longer after the funding runs out.

8. If funding were not an issue, what would you add to your project?

Lexi: Ideally I would want to recreate the oil spill in a contained micro environment simulating the Gulf of Mexico. This way you could expose a variety of organisms, particularly commercial fish and prey species, to oil and COREXIT over an extended period of time. I would then do extensive analysis on the fish to determine exposure levels for a multitude of compounds marking oil and COREXIT exposure. These fish could also be used for reproductive studies to determine the effects on the next generation.

Demetri: Point blank range, we would “go big” on what we are doing right now: we would combine our current studies on obesogen identification and stem cell differentiation to look at all components of COREXIT and a wide array of crude oil components. Working with dispersants, we would replace obesogenic components of COREXIT with new dispersants/ solvents that are currently being produced by GoMRI researchers to test the safety of these new agents. On the crude oil side, molecules found to be obesogenic could then potentially be targeted for breakdown or inactivation. We would expand from working only with obesogens to working with other hormone disruptors, especially including pollutants commonly found in the Gulf (e.g. herbicides/pesticides). This information could then be used in modified toxicological testing to identify “safer” dispersants and safer crude oil and oil products.

Other avenues we might consider are tests from the stem cells of different organisms (e.g. human, marine mammal, shore birds, estuarine alligators, seafood, etc.) with different exposure histories, which might tell us if (and why) a species is  particularly sensitive or resistant to the obesogens and thereby used to follow or even alter the rise and fall of species. With substantial funds we could also test over several generations to assess the long-term health impacts on one organism (e.g. reproductive development/fertility, disease, cancer, longevity, etc.), but also impacts on offspring several generations out. We’ve also been looking at ways to by-pass the use of animal species for these studies, which is more ethical and could speed up how quickly we improve our understanding.

9. What are your future hopes?

The work discussed may serve as one of several foundations for making us better stewards of the planet – working at the interface between product development and human health, which ultimately relies on proper environmental/ecosystem management.

[Back to the Spring 2014 Newsletter]