Nicole Soucy PhD

June 2002

Canoe exploration set student’s academic course

It was a Gifted And Talented high school course on aquatic biology that first sparked Nicole Soucy’s ambition to become a scientist. Traveling through Maine’s waterways by canoe, she learned to map the changes in water quality and wildlife as the class moved from inland stream where the group pushed off, to the ocean, where the trip ended. Exploring by canoe became an exploration in science and Nicole has ended up a graduate research associate working on her doctoral thesis in Aaron Barchowsky’s lab in the Pharmacology/Toxicology Department of Dartmouth Medical School.

Now instead of looking at water quality from an ecological view, Nicole studies one of the human health effects of contaminated water — illness from chronic arsenic exposure. It has been long documented that large doses of arsenic can cause lethal poisoning by triggering cell death. However, in areas of the world with low levels of arsenic in the drinking water, scientists have documented that arsenic can lead to tissue growth. Nicole’s research group, which is part of the Center for Environmental Health Science’s Toxic Metals Research Program is trying to explain a scientific curiosity while working on something that affects local citizens — toxic metal exposure through drinking water. The group is specifically looking at how low levels of the most toxic form or arsenic, called arsenate, affect functioning of blood vessels.

Nicole studies the endothelial and smooth muscle cells that line blood vessels. She looks at how certain growth-promoting proteins are secreted by particularly the smooth muscle cells to aid in angiogenesis, or the formation of new blood vessels, when the tissue is exposed to arsenic. These proteins that cause angiogenesis are a natural part of blood vessel tissue regeneration. But what happens when angiogenesis occurs when and where it’s not supposed to? Imagine drinking a soda from a straw and then trying from a plastic coffee stirrer. You can still drink the soda, but it takes more effort to draw it through the smaller hole of the coffee stirrer. In the case of blood vessels, Nicole has been able to show how increasing levels of arsenic lead to increasing levels of the angiogenesis growth factors, which can mean growth of vessel wall tissue to the point that the vessel’s space, or lumen, becomes constricted. High blood pressure, heart disease, and diabetes can ensue.

At the moment, the researchers are still looking at the exact mechanism that arsenic initiates to promote excess vessel growth. To do this, they must look at the response of vessel cells to arsenic. The first step is to prepare cells for research. Nicole takes cells from a pig aorta and cultures them to produce more cells. She then freezes them and takes some out to grow when it’s time for an experiment. She exposes the vessel cells to arsenic, as they would be through the blood stream if the pig (or a human) were drinking contaminated water. Next, she collects the RNA from the exposed cells and runs them through an RT-PCR machine that transcribes the RNA back to DNA (the reverse of a normal process). This way, she now has only the DNA sequences that encode for the particular RNA strands that encode for the angiogenesis growth factors. In other words, to look at the genes that encode for angiogenesis growth factors, she must work backwards from growth factor to RNA to the DNA. The RT-PCR machine amplifies the DNA once it’s been reverse-transcribed from the RNA so that the genes will be present in a high enough concentration that they can be studied. Using this state-of-the-art gene amplification technology, she is able to study the genes that encode for these particular proteins that switch on angiogenesis.

“If you don’t plan well, you might have to come back into the lab at four in the morning if something needs to be checked or taken care of,” Nicole says of research like this. And work like this doesn’t stay in the lab either. “You do an experiment and you get the data then you go home and out of the blue on a Saturday morning you figure everything out. You think, that’s why it did work or that’s why it didn’t. It’s not the type of thing you can just go home and forget about.”

Nicole and the other researches have also shown that blood vessel endothelial cells also can migrate to non-vessel tissue that has been implanted in a mouse when the mouse is exposed to arsenic. They implanted what is known as matrigel, deactivated cancer cell tissue into the mouse and found that it began showing angiogenesis with arsenic exposure. They then removed the piece of tissue and counted the number of blood vessels that had formed. There is a correlation between the number of blood vessels and the level of arsenic that the mouse received, reinforcing the hypothesis that low levels of arsenic promote angiogenesis.

Nicole would like to eventually get a teaching position at the university level, but this summer she will spend a day with students at a Montshire Museum summer science camp teaching them about her work and giving them data sets to interpret. Public outreach is an important component of the work of CEHS and Toxic Metals Research Program members and close collaboration with the Montshire Museum is just one way they do it. The students will be given very similar data to what Nicole really uses. Nicole is allowing the students to get a feeling of what science is all about and let them feel as though they are a part of the research. Who knows, she might inspire a student to pursue this science exploration further, just like what happened to her in a canoe in Maine.

Bethany Fleishman
CEHS intern

Publications during training:

Barchowsky A, Soucy NV, O’Hara KA, Hwa J, Noreault TL, Andrew AS. 2002. A novel pathway for nickel-induced interleukin-8 expression. J Biol Chem 277:24225-24231.

Soucy NV, Andrew AS, Barchowsky A. 2001 Nickel induces IL-8 expression in human airway epithelial cells. The Toxicologist 60:317.

Soucy, NV, Klei LR, Barchowsky A. 2001. Mechanisms for arsenite-stimulated vascular cell angiogenic and profibrotic gene expression. Free Radic Biol Med. 31:S62.

Soucy NV, Ihnat MA, Kamat CD, Post MJ, Klei LR, Barchowsky A. Arsenic stimulates angiogenesis in vivo. Submitted 2003.

Awards and presentations during training:

2001 - Young Investigator Award, The Oxygen Society, for “Mechanisms for arsenic-stimulated vascular cell angiogenic and profibrotic gene expression.”

2002 - Third Place, Student Poster Awards, Metals Specialty Section, “Potential cellular mechanisms for arsenite-induced vascular diseases.” Society of Toxicology Meeting, Nashville, TN.

2002 - Poster presentation, “Signaling mechanisms for arsenite-induced cardiovascular disease,” The Oxygen Society meeting, San Antonio, TX.

Current Position: CIIT Centers for Health Research