Scientists at West Virginia University are researching ways to fine-tune how cells use the simple sugar glucose and determine how the process is sometimes disrupted, leading to diseases such as cancer, diabetes and inflammation. By defining the mechanisms that control this pathway, the researchers aim to identify new strategies for therapeutic intervention.
“The big picture we’re trying to understand is how cells use glucose to fuel different needs, from making the building blocks of new cells to making energy for the body to use,” Bradley Webb, assistant professor in the WVU School of Medicine Department of Biochemistry and Molecular Medicine, who leads the study, said.
“We also want to know how glycolysis — the metabolic process of breaking down sugars and converting them into energy — can contribute to the disease process and how cells might hijack this process in different diseases.”
Webb said researchers hope that targeting enzymes involved in glycolysis could be a way to treat disease. But they first need to understand how those enzymes are regulated.
To gain insight into the regulation, Webb is working with Elena Pugacheva, associate professor in the Department of Biochemistry and Molecular Medicine and WVU Cancer Institute. They will investigate connections between filament structures formation and cancer cells metastasis, with the goal of identifying new mechanisms linking metabolic organization to cancer progression. The team is also collaborating with Justin Kollman and Eric Lynch in the Department of Biochemistry at the University of Washington to integrate structural and biochemical analyses.
Webb’s study focuses on the enzyme phosphofructokinase (PFK1), an enzyme often described as the “gatekeeper” of glycolysis. Because PFK1 helps control how cells process glucose, understanding how it is regulated is central to the work.
A study led by Heather Hansen, a postdoctoral researcher in Webb’s lab from Dallas, Texas, suggests that the ability of PFK1 to be “recruited” by cells for help with the process of glycolysis is dependent on its ability to form these filaments.
Webb explained that although cells form filaments and other structures to organize their metabolic pathways, how PFK1 contributes to filament formation and how that affects its function remain unclear.
“Without PFK1, we think cells can’t respond to signals from the environment that say, ‘migrate this way’,” Webb said. “Through our study, we are asking fundamental questions about the organization of the cell, which can lead to insights into how our cells actually make decisions.”
Webb’s study is funded by a five-year $1,912,500 R35 grant from the National Institute of General Medical Sciences.
In addition to Hansen, Donald Dariano, a fifth-year doctoral student from Hanover, Pennsylvania, and Kyle Wheeler, a senior undergraduate student from Parkersburg, are contributing to the project. Webb is recruiting additional undergraduate students to join the research team.
“I think the idea that potentially we could fine-tune our cells’ use of glucose to prevent certain diseases or turn down certain cellular processes is intriguing,” Webb said. “I’m studying how the cells use these pathways so we can potentially identify metabolic weaknesses.”
-WVU-
MEDIA CONTACT: Linda Skidmore
Health Research Writer
West Virginia University Health Sciences
Linda.Skidmore@hsc.wvu.edu
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West Virginia University students, from left, Heather Hansen, Donald Dariano and Hayden Hess, assist with a study in Bradley Webb’s lab to determine how cells use glucose to fuel different needs. (WVU photo)