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Dr. Ke Dong: From Silkworms to Toxicology

By: Ariella Ruiz

At the Dong Lab, the principal investigator Ke Dong has had an interesting journey through her studies and research. While interviewing her this week, I learned more about how she became interested in her field of science and research. She recently moved from Michigan State University to Duke, so we also spoke about that transition and what her long-term goals for her lab are. Dr. Dong is an excellent person to talk to about how to take your life long or childhood passions and turn them into a career.

**I have paraphrased her answers to keep this post concise and focused on the key elements of her responses.

Q: Where did you do your undergraduate and graduate studies? What was your major?

I completed my undergraduate studies in China as a biology major with a focus on entomology. After undergrad, I received my Master’s in entomology at a graduate school in China, which was a three year program. In 1988, I came to the United States to attend Cornell University for a five year Ph.D. program. “I was an entomology major and a toxicology minor for my Ph.D. After that my research was more focused on neurotoxicology, so toxins that act on the nervous system. That includes many classes of insecticides (they are neurotoxins), and then also natural toxins like scorpion toxins and venoms.” 

 In total Dr. Dong completed 12 years of higher education.

Q: What drew you to your field of study? What are you passionate about?

I grew up on a university research station in China for students studying silkworms and mulberry trees. My mom was a professor there, a biochemist. The silkworms were my pets; that’s how I got interested in insects. When I was in high school I started helping with the research- “dissecting the silkworm to find out all the different internal organs and figure out the glands that secret their silk. I found it fascinating. Many people don’t like insects, but for me I like insects.” My interest in toxicology specifically began from two different incidents during my childhood. First, the village near the research campus grew rice, and the farmers sprayed Bt toxin on the crop. The pesticide managed to travel to the campus by wind and kill some of the silkworms that were being researched. When I observed this, I wanted to know why they died and the mechanisms behind it. “Another situation was when a farmer in the village got really sick by using some early class of insecticide- organophosphate. It was a spray; they did not use it right and a bunch of people got really sick. So I witnessed a lot of these and was wondering what was happening with the toxins? My fascination with toxins started a really long time ago, but I did not get a chance to do that kind of research in China. I did do physiology, entomology, and a bunch of different things, but the toxicology work I actually started at Cornell. I was always interested in why toxins are toxic, why are they so lethal. Why don’t some toxins just make you sick but kill you instantly?” 

Q: When did your interest in research start? 

My interest in research sparked during my Ph.D. program in a toxicology lab. I was interested in learning not only the physiological effects of toxins but the molecular aspects of their functions as well. My first molecular lab experience was during my Ph.D. program because there weren’t many opportunities for me during my master’s program. It was exciting to use PCR (which was fairly new at the time) and other molecular techniques to address some important toxicological questions at the molecular level.

Q: How did you start your lab at Michigan State?

My husband is a plant biologist, and he received his Ph.D. a bit earlier than I did. When I graduated, he started an assistant professor job at the University of Kentucky. I followed him there and began working as a postdoc. The lab I started working in was nice but didn’t really fit my interests. After a bit, I spoke to my Ph.D. mentor from Cornell who suggested I continue my research from Cornell at Kentucky. However, to start my own research I needed funding. I submitted a grant proposal to the National Science Foundation (NSF), and fortunately, my proposal was funded. While I could have continued my Ph.D. work at Kentucky, I wasn’t happy at the university. There was racism from the department administrator at the time that prevented me from enjoying my work. Luckily, both my husband and I were offered jobs at Michigan State University (MSU). I used my NSF grant there to continue my Ph.D. research; we were both at MSU for 25 years. 

Q: What was your project at Michigan State?

At Cornell, I started a project studying a strain of German cockroaches which was highly resistant to DDT and pyrethroid insecticides. “At the time nobody knew why these insects developed resistance.” I focused on DDT and pyrethroids (an ingredient in common insecticides) which target insect sodium channels and kill the insects. “The hypothesis was maybe something changed in the sodium channels. Maybe there were more sodium channels or less sodium channels or mutations in the sodium channels. There were all these different hypotheses.” In my research, I found that there are likely mutations in the sodium channels and that’s what makes them resistant. At the time I wrote the SF grant, my goal was to identify the mutations. When I settled at Michigan State and started identifying mutations, it turns out there wasn’t one or two mutations like originally believed but actually a lot more. “We were only looking at the sequences, but people said ‘How can you confirm that this mutation makes cockroaches resistant?” So that is why in Michigan I set up a Xenopus oocyte system and expressed insect sodium channels for functional characterization and examination of channel sensitivity to DDT and pyrethroids. It was technically very challenging; even now only a few labs in the world can express insect sodium channels in oocytes. That was our advantage. We kept going with different mutations. We kept going with different sodium channels from different species because many past species develop resistance. We also want to understand selectivity. Why are they more toxic to insects, less toxic to humans? So we look into mammalian sodium channels.” Mammals have nine sodium channel genes, and we wanted to understand why human sodium channels are relatively resistant to pyrethroids. In the lab, we discovered that the receptors on the mammalian sodium channels aren’t good for the pyrethroids to bind to and take effect. While studying sodium channels, we discovered the function of a new ion channel called Drosophila Sodium Channel 1 (DSC1). The DSC1-family ion channels seem to be unique to insects, and there are no orthologs in mammals. It is would be a good target for insecticides that can be relatively safe for humans. 

Q: What was the transition from Michigan State to Duke like? Why did you come to Duke? 

While both my husband and I had productive careers at Michigan State for 25 years, both of us wanted some changes personally and professionally. I wanted to live in a warmer climate for health reasons. Over the years, we had both been offered jobs elsewhere but never at the same place. Duke was an opportunity for both my husband and I to move and have positions together. There are also more opportunities to collaborate with colleagues at Duke.

Q: What are your long-term goals for your research?

My long-time research focus has been on controlling mosquitoes that transmit human diseases. Insecticides kill mosquitoes and in turn mosquitoes develop resistance. Repellents are very important too because they can reduce human contact with mosquitoes; therefore, reduce disease transmission. I’ve been studying the mechanisms of actions of insecticides and repellents on the insect nervous system including the olfactory system. So far, we have a much better understanding on how insecticides kill mosquitoes. How exactly repellents repel mosquitoes at the molecular and neuronal levels are largely unknown. In the next five to ten years, I hope to identify more receptors that mediate repellency and use it to develop more repellents. Currently we are only able to look into mosquito antennas, but we are working to establish new techniques in the lab to study the effects of insecticides and repellents on the function of the brain. We hope to open mosquito brains to look at the neural circuits to see how they are activated by insecticides and repellents, and how this leads to certain behaviors, such as avoidance behavior, observed.

Q: What has your experience as a professor been like? 

I love it. I’ve only taught one semester at Duke since I’ve been here. It was a seminar course about natural neurotoxins. The course discussed toxins produced by spiders, snakes, scorpions, etc. and the ion channel receptors that are targeted by those toxins for their toxic actions. Most of the students were engaged, and we had fun. This was also the first time I taught undergraduates because at Michigan State I only taught graduate courses. “Being a professor at a university, interacting with students is quite fun and a unique opportunity.”

Q: What advice do you have for someone who is considering a career in research?

“Find a research area that one is really interested in, work with experts in that field if possible and work diligently.”

While interviewing Dr. Dong, she exuded passion for science and love for her projects. She’s excited for the future of her research and the possible discoveries that can be made in the upcoming years. Dr. Dong is highly motivated and ambitious, and I’m grateful to have her as my PI; I have much to learn from her this summer.

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