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Student-faculty Research Team Assessing Early Markers and Dietary Treatment of Liver Cancer

Non-alcoholic Fatty Liver Disease (NAFLD) is an early indicator of Metastatic Hepatocellular Carcinoma, the fastest-growing type of liver cancer globally. Understanding the impact of diet on the disease could help lower cancer rates long-term.

By Monique Kleinhuizen '08, GS'16, new media strategist

June 12, 2020 | 9:45 a.m.

Student Korbyn Dahlquist ’20 is part of a research team developing less-invasive test for non-alcoholic fatty liver disease (NAFLD).

Student Korbyn Dahlquist ’20 is part of a research team developing less-invasive test for non-alcoholic fatty liver disease (NAFLD).

“We can’t really take vacations. The cells need to be taken care of. It’s like having a dog,” Korbyn Dahlquist ’20 explained with only a hint of sarcasm last summer. At the time, the biochemistry and chemistry double major and Associate Professor of Chemistry Angela Stoeckman were embarking on a year-long Edgren Scholarship-funded research project focused on understanding the dietary influence on markers of metastatic hepatocellular carcinoma. 

To achieve that, the team has been treating liver cancer cells—“H4IIE,” which can be bought online through distributors—with control substances or a saturated fatty acid called palmitate. The hope is to determine when cells are going through apoptosis—dying because of the presence of extra lipids—and if they’re secreting an anti- or pro-inflammatory response in the form of cytokines. That’s like a chemical “call for help” that could flag the presence of further injury through a simple blood test.

To create the ideal setting for this type of work on fussy mammalian cell cultures, the team has created an intricate and incredibly hands-on process of sterilizing a biosafety cabinet with UV rays before growing cultures in optimal conditions over several days. Then they have to time their assays perfectly with the death of the cells to get the data they need.

They stain the apoptotic cells with fluorescent markers and run them through a flow cytometer. A million cells can be run through the machine at once, and it quantifies the amount of lipids present in specific populations, within a split second. 

“If people with the cancer have high levels of a certain cytokine, there’s morbidity in the disease,” Stoeckman explains. “If person A is secreting, and B is not, perhaps A is more likely to die from their cancer. What Korbyn is noticing is that if these cancer cells are seeing palmitate, a saturated fatty acid, that’s inducing them to secrete more cytokines, which is responsible for high morbidity. And maybe we can keep cytokines under control simply by recommending a certain diet!”

NAFLD is a condition that impacts an estimated one in three Americans, and it can progress into hepatocellular carcinoma, the fastest-growing type of liver cancer globally. It’s responsible for the third highest number of cancer deaths, so detecting NAFLD early could mean saving lives in the long term. Currently, it can only be identified by biopsy, which is both invasive and expensive. 

The project is an extension of Stoeckman’s graduate work, which focused on fatty acid metabolism, and her post-doctoral research in immunology. She explains that while hepatitis B and C are historically a common cause of liver cancer, those instances are decreasing because hepatitis immunizations are becoming more common. However, alcohol- and diet-related conditions are now being linked more strongly to liver cancer. A high-carbohydrate, high-fat diet—that’s especially high in high-fructose corn syrup—has been dubbed the “Western Diet,” Stoeckman says. It’s been blamed in recent years for the uptick in liver cancer. She adds that there’s sometimes a conflict between researchers, the food industry, and popular opinion.

“There’s just so much out there that says ‘eat low fat’ or ‘cholesterol is bad,’ and so on. I don’t think people know who they can trust. As a Christian who is a biochemist, there’s a heavy burden on a person like me to say ‘this is what we’re seeing. This is the data.' If our research comes out to say, definitively, ‘if you have NAFLD and it turns into cancer, the best thing you can do is decrease your glucose,' I hope they see. I hope it saves lives.”

— Associate Professor of Chemistry Angela Stoeckman

Cell studies are effective for this type of research, but whole animal studies are even more definitive, so the team has worked closely with researchers at the University of Minnesota who are tracking the metabolic responses of mice to NAFLD. Dahlquist has been a part of the project for a year and a half, focusing her senior capstone project on the work and planning to present it at the American Chemical Society meeting in Philadelphia in March. That meeting was canceled due to COVID-19, but the pair has been able to continue its work testing specific inhibitors through funding from the Edgren Scholar program. 

The pair has presented their work at the Associated Colleges of the Twin Cities summer chemistry symposium. Dahlquist has presented it at the Big Ten Lipid Alliance meeting at the University of Minnesota. And they’re considering submitting it for publication in the Cancer Letters or Anti-Cancer Research journals, something COVID-19 has given them more dedicated time to do. Stoeckman has also involved her spring Course-based Undergraduate Research Experience biochemistry class in the work. It’s a project that has potential for many Bethel students to get involved—and one that could have significant implications in the medical world. 

“What’s most exciting is Korbyn’s word of mouth, spreading the word and talking about what she did last summer. Students say, ‘Oh wow, you got paid to do research at Bethel?’” Stoeckman says. “She’s going to grad school, where they might get 20 applicants with 4.0 GPAs. They see that Korbyn did a 1.5-year research project, and that sets her apart, even more than her GPA or double major. At bigger schools, you just don’t get these kinds of opportunities, and it’s awesome to have a little funding to make these things happen.” She also mentions the benefit of having cutting-edge equipment—like the flow cytometer donated by Dr. Robert and Phoebe Love and the microplate reader that does fluorescence and luminescence analysis. 

“We could not do our work without new technology,” Stoeckman adds, joking that they’ve gotten so close to two of their pieces of equipment that they’ve dubbed them “Cinderella and the Ugly Stepsister.” All jokes aside, it’s these types of equipment that keep the work running and students attracted to schools like Bethel. She’s working with Professor of Biology Joyce Doan to apply for a grant to fund additional technological capabilities in the departments of biology and chemistry with the opening of the donor-funded science addition this coming fall

To Stoeckman and students like Dahlquist, there’s something amazing about the high-tech research relationships that are built within Bethel’s labs, and they’re excited to see that scale up along with the addition. “Sometimes I walk in at 10 at night, and someone’s still there in the lab working,” says Dahlquist, who graduated in May and starts graduate studies in biochemistry at the University of Minnesota in fall. “I can ask them any question about my research, and it’s understood that there’s an open door policy. Everyone is so open and helpful, truly wanting us to succeed.” 

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