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Can researchers better utilize our cellular powerhouses to fight infection? Yes, according to this podcast, but it’s all about timing and balance. James Phelan’s research into when cells utilize glycolysis and what that might achieve for infectious diseases has turned the cancer field on its head. Listen in to learn about metabolic pathway research that has therapeutic-changing potential.

He addresses

  • How he characterized cellular metabolism along the sequence from Barrett’s esophagus to esophageal cancer,
  • Why the discovery of cells primarily using glycolysis for energy at a key point in the disease progression was a major finding, and
  • How this finding translated to tuberculosis (TB) research and a way to fight infection in its early stages.

James J. Phelan is a postdoctoral research fellow at Trinity College in Dublin. He spent most of his PhD work developing an expertise in cellular metabolism, specifically in the context of esophageal cancer. He explains how he carefully examined the metabolic pathways accompanying the progression from Barrett’s esophagus to cancer of the esophagus. Barrett’s esophagus, or intestinal metaplasia, indicates a distortion of cells and is the biggest risk factor for esophageal cancer.

He found that as patients progress from this inflammatory esophageal condition to cancer, their cells use an aggressive form of metabolism called glycolysis, which involves a higher flux of cytokines and chemokines, both damaging to tissue. In other words, glycolysis is a cancer-specific form of metabolism.

He brought this findings into the infectious disease and immunology field and found that glycolysis has a contrasting role in an infectious disease context. However, it started with a similarity: as with cancer patients, infectious disease patients are burdened with high inflammation. The goal of therapeutics is to reduce inflammation, particularly with TB, one of his specialties.

Here’s where it gets tricky and innovative: if glycolysis as the main metabolic pathway is turned on early for TB, it will help eradicate the infection. They’ve found an iron binder in clinical trials for COVID-19 that can turn on glycolysis in macrophages infected with TB and clear the infection. By using this compound, they can switch on glycolysis and turn on cytokines, which are actually very harmful in the late stage of TB. But in the early stage, they are curative.

He explains this surprising finding in more detail as well as therapeutic possibilities such as in vaccinations and other ways this research may help inform vaccines and the immune response.

For more, see his website at Trinity College.

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