Sunad Rangarajan, MD

Healing lung tissue after injury depends upon a steady supply of energy, which comes from mitochondria—parts of cells that turn oxygen and nutrients into fuel. Our research focuses on how disruptions in metabolism and mitochondrial function lead to the activation of cells called fibroblasts, resulting in destructive scarring in lung fibrosis associated with rheumatoid arthritis, an autoimmune condition that affects multiple organs. Understanding this process can lead to new treatments that will slow or halt this scarring.

Innovation Award, applied under the Hastings Award

Update: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) causes progressive, irreversible lung scarring (fibrosis) and remains poorly understood. Our research investigates how disruptions in the energy metabolism of lung fibroblasts, the cells responsible for scarring, drive disease progression. Working with patient-derived fibroblasts, our team found that fibroblasts from people with RA-ILD are overactive and contribute to lung scarring. Examining fibroblast from both healthy people and people with IPF, we found that these cells also share important weaknesses in the way they produce energy. We also discovered that changing the activity of a key enzyme called PDK1 reduces collagen production through an unexpected mechanism involving how the protein is processed within the cell rather than how it is genetically encoded. These findings are shaping our next phase of investigation into novel therapeutic targets for RA-ILD.