Student Spotlight: Mitchell Studies How Repellents Affect Gene Expression in Human Liver

For Robert Mitchell, getting to conduct research at NC State University at the crossroads of human health and insect science has been something of an unexpected, but rewarding, experience.

Through an award-winning study he conducted with entomologist R. Michael Roe, Mitchell has helped shed light on how insect repellents affect gene expression in human primary liver cells.

With the rising concern about the mosquito-borne Zika virus, the research is particularly timely. That’s because women who live in areas affected by the virus and who are pregnant or planning to become pregnant may be tempted to use mosquito repellents at rates that have not been considered by researchers before.

Mitchell, who earned his Ph.D. in entomology in May, says that while the research doesn’t predict the health effects of using repellents more frequently, it does provide a starting point for further research. And it gives him a springboard for the scientific career he’s been working toward for years.

How did you get interested in entomology?

It wasn’t that I was particularly interested in entomology at the time, but when I was about six months away from my undergraduate degree, I went to Old Dominion University (Norfolk, VA) and just started walking around to see if anybody was looking for help. I ended up walking into Dr. Daniel Sonenshine’s lab, and he was working with ticks. He had me dissect a tick under a microscope, and it was super small. I thought, ‘This is really different from anything I’ve done before, but it’s kind of fun.’ Dr. Sonenshine said, ‘Well, if you can dissect a tick, you’ve got a job.’

I worked for him for several years and fulfilled all the requirements for a master’s degree except for the defense. In lieu of completing the master’s degree (a decision I regret), I immediately entered the Ph.D. program at Eastern Virginia Medical School. But toward the end my father was sick – he actually passed away – and I was unhappy with where I was and didn’t know what to do.

I made contact with Mike Roe – I had worked with him while I was at Old Dominion because he collaborated with Dr. Sonenshine, and I had great respect for his knowledge and tenacity. He said, ‘Why don’t you come down to Raleigh and give entomology a try?’ So he gave me the opportunity to put my toe in the water with entomology, because I’d been working exclusively with human tissue and human-derived cell lines.

It turned out to be a great decision and has completely transformed my life and career goals.

What did you find through your research?

What we have been looking at is the effect of some common pesticides on primary human liver cells. Unlike other studies, we used cells straight out of the human body that haven’t been modified in any way (that is, primary cells), so it could be closer to what would happen in the human body. We are treating the cells with some common chemicals – DEET, which is a widely used repellent, and fipronil, which is used on dogs and cats for flea treatments and around the home for termite control.

If people are scared and using more than they should on a daily basis, we just don’t know what the long-term effects are. And that’s what we have been trying to determine. We found that at the transcript level there’s a lot of activity involved in metabolizing these chemicals, and the combination of the DEET and fipronil can have a more-than-additive effect. We found that when there’s more than one chemical, there’s a lot more gene activation. So your body is working harder than it would if you were exposed to each chemical separately. Genes on every chromosome were affected, and also genes that are involved in the regulation of other genes were affected. There were some surprising results that need further investigation relative to their potential impact on human health.

This is the first study I’m aware of … looking at the effect of environmental chemicals on primary cells in this capacity. A lot of what we base our knowledge on is animal models, immortalized cells lines, things that are pretty far-removed from your body. So this is an attempt to be a much closer model to what’s going on in the human body. Also, this type of research could assist in developing a prognostic, diagnostic or therapeutic method for exposure to these chemicals.