Andrea Hunger, an IPiB graduate student, will be defending her Ph.D. research on May 19, 2025. Her research in the Simcox Lab focused on a lipid translocase protein — an enzyme that facilitates the movement of lipids within a cell. Hunger examined the protein’s role in toxic lipid buildup in the cell.
Acylcarnitines are lipids that are found in elevated levels in blood plasma under chronic stress conditions (such as heart disease and diabetes) and acute stress levels (such as exposure to cold and fasting). When acylcarnitines build up to toxic levels, they can inhibit insulin signaling and can cause cell death. Some cells have a higher threshold for tolerating acylcarnitines. The mechanisms responsible for why some cells survive high levels of acylcarnitines and others do not are unknown.
Researchers in the Simcox Lab used a CRISPR screen to identify the genes involved in metabolizing acylcarnitines. The screen showed that CD36, a protein that helps shuttle lipids into the cell and to various organelles, is associated with a cell’s ability to survive toxic levels of acylcarnitines. Hunger used this data to further explore CD36’s role.
Hunger found that the absence of CD36 results in greater acylcarnitine sensitivity. These unexpected results suggest differences between cellular membranes and the membranes of mitochondria, where acylcarnitine is metabolized. “There is redundancy across the cell membrane for transporting lipids, so even if we knock out CD36 it will still be possible for acylcarnitine to get into cells,” explains Hunger. “But that redundancy may not exist in the mitochondrial membrane.”
Hunger believes that in the absence of CD36, acylcarnitines can enter the cell but cannot then be transported to the mitochondria to be broken down. The result is a toxic buildup of acylcarnitines in cells.
“Now we know something new that can help with developing effective lipid metabolism inhibiting drugs,” says Hunger. “We’d want to avoid drugs that target the mitochondria, because that could exacerbate some diseases.”
Hunger’s path in graduate school was not linear. She joined the Simcox Lab in her final year and a half of graduate school, and her research focus pivoted. Through challenging times, it was scientific curiosity that fueled her. “There are always times along the way that you wonder if it’s going to be worth it — those nights when you’re in the lab until later than you thought you’d be — but in the end it’s the same curiosity I had that first time I looked in a microscope that keeps me going.”
Organizations within and outside of IPiB played an important part in Hunger’s time in graduate school. She served as chair of the Graduate Leadership and Development Committee (GLDC) and taught at the Morgridge Institute’s Summer Science Camp for underserved high school students for two years, including students from rural communities.
In exploring her career interests, Hunger completed an internship on the research and development team at the Madison branch of Illumina, Inc. as a Biotechnology Training Program trainee. “I was interested in learning more about a career in industry, so I’m grateful that I had the opportunity to do an internship and see what that would really be like,” reflects Hunger. She will be joining the cell and gene therapy team at PPD Laboratories, which is based in Middleton and was acquired by Thermo Fisher Scientific in 2021.
To learn more about Hunger’s research, attend her Ph.D. defense, “Exploration of novel genetic regulators of metabolism” on Monday, May 19 at 10:15 a.m. CT in Room 1211 of Hector F. DeLuca Biochemical Sciences Building.
Written by Renata Solan.