This profile is part of a series focused on Brown faculty and students engaged in science and research, with the purpose of highlighting and making more accessible the work being pursued at all levels across disciplines.
Many compounds in the environment — whether ingredients in food or materials that make up everyday objects like plastic water bottles — could be harmful to humans, but have never been tested, said Samantha Madnick, a senior research assistant in Professor of Medical Science Kim Boekelheide’s lab.
Madnick works with a team of scientists in the Boekelheide Lab to explore the potential of 3-D cell cultures to create quicker and cheaper screens for toxicants, man-made chemicals that may be toxic to the body.
Current screening methods rely on animal models, which are time-intensive and expensive, explained her co-researcher Maggie Vantangoli GS. To explore the effect of a substance on the liver, for instance, researchers must expose animals to the toxicant, wait for effects and then excise cross-sections of the liver to examine it.
“The idea is that you can do quick in-vitro screens” with 3-D cell cultures to bypass the time and money required for animal testing, Vantangoli said.
“Hopefully with more technology we can eventually test new chemicals before they go on the market,” Madnick said, adding that these important health implications are what she finds most rewarding about their work.
Using technology originally developed by the Morgan Lab at Brown, the team of researchers is using 3-D cell cultures to examine the effect of toxicants that may interfere with the body’s estrogen. Many of the compounds have a similar structure to estrogen, and could physically block estrogen from binding to the proper receptors in the body by attaching to the receptors themselves.
“By using these human cell lines in a really simple, inexpensive and relatively quick model, we can assess the potential endocrine toxicity of a lot of different compounds,” Vantangoli said.
The 3-D cells paint a clearer picture of toxicants’ effects than 2-D cell cultures, another current option for toxicology testing, said Shelby Wilson ’15, a member of the research group.
They also create a more reliable image than other types of cultures that rely on an external scaffold, as these types of scaffolds are not present in the body, she added.
The lab’s 3-D cultures arrange themselves in a similar conformation to body tissues and even retain some of their functions, Vantangoli said. For example, her group has created breast cell cultures that could secrete some milk proteins.
As part of their work, the researchers examine whether exposure to suspected toxicants causes the cell cultures to retain the same shape as cell cultures devoid of those toxicants.
“If you have a change in structure, you’re going to have a change in function,” Vantangoli said.
Wilson pulled out a box full of slides to demonstrate some of the changes the toxicants might cause. First, she placed a cell culture lacking toxicants under the microscope. A series of small, red, circular blobs sat in the shape of a donut.
Next, she picked a slide of cells exposed to a known toxicant. These cells did not arrange themselves with an open center, but instead formed solid blobs.
The researchers spend a lot of time determining how best to use the new technology that 3-D scaffold-free cultures provide, Wilson said. Varying cell strain and density can allow them to optimize their screens.
“I like that it’s a new technology and a growing field,” Vantangoli said.
A previous version of this article incorrectly referred to toxins instead of toxicants in one instance. The article also incorrectly described a slide of cells as infected with a toxicant. In fact, it was exposed to a toxicant. The Herald regrets the errors.
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