Eric S. Goetzman, PhD, Research Projects

The regulation of fatty acid oxidation and its implications for diseases such as diabetes and obesity has been a key focus of Eric Goetzman, PhD.

Current Research

Cancer Metabolism

Otto Warburg observed in 1924 that cancer cells have an unusual reliance on glycolysis for energy. He believed this metabolic switch to be indicative of a defect in mitochondrial oxidative metabolism. More than 90 years later, researchers still do not understand how and why cancer cells alter their metabolism or what role changes in mitochondrial energy metabolism play in the etiology of cancer or in the ability of cancer cells to escape apoptosis. Answering these questions may reveal cancer’s Achilles’ heel and lead to a cure. Our team is collaborating with Edward V. Prochownik, MD, PhD, director of Oncology Research at UPMC Children’s Hospital of Pittsburgh, to study how the oncogenic transcription factor c-Myc drives cells toward an anabolic metabolic phenotype. This may involve changes in mitochondrial enzyme lysine acetylation as well as changes in partitioning between glucose, glutamine, and fatty acid metabolism.

Principal Investigator

Eric Goetzman, PhD

Fatty Acid Oxidation in the Lungs

In mouse models, those “knocked out” for the fatty acid oxidation (FAO) enzyme LCAD demonstrate reduced lung function. Our research team hypothesizes that LCAD and the FAO pathway are involved in synthesizing and secreting pulmonary surfactant in a specialized lung cell known as the type II pneumocyte. Surfactant is a mixture of phospholipids and proteins that reduces surface tension in the lung. This effect is necessary to prevent the collapse of the alveoli and promote gas exchange. LCAD knockout mice have reduced amounts of surfactant lipids and an altered phospholipid composition. Preliminary studies show an increased susceptibility to infection by influenza. Efforts are underway to determine the molecular mechanisms behind these changes.

Principal Investigator

Eric Goetzman, PhD

Mitochondrial Metabolism Regulation

Regulation of Mitochondrial Metabolism by Reversible Lysine Acylation

A core focus of our laboratory studies is mitochondrial fatty acid oxidation (FAO), the pathway by which fatty acids are broken down for energy. Mutations in the FAO genes are among the most prevalent inborn errors of metabolism. Recently, it was discovered that the FAO enzymes are heavily modified by post-translational modifications, including lysine acetylation and lysine succinylation. There are three mitochondrial sirtuin deacylases (SIRT3, SIRT4, SIRT5), which are believed to reverse some of these modifications. The lab’s current research focuses on the functional effects of lysine acetylation and succinylation on the FAO pathway and the role the sirtuins play in regulating metabolism.

Principal Investigator

Eric Goetzman, PhD