Welcome to the Kliment Lab!

The vision of our research program is to determine how mitochondria orchestrate epithelial repair, cellular senescence and immune cell function in diseases of accelerated lung aging to identify new therapeutic approaches.

Dr. Kliment’s laboratory is interested in identifying new molecular pathways connecting mitochondrial function with epithelial repair, cellular senescence and innate immune cell function in the pathogenesis of chronic obstructive lung disease (COPD) and pulmonary fibrosis to improve therapeutic options for patients. Our lab specifically studies the role of adenine nucleotide translocase (ANT, a canonical mitochondrial ADP/ATP transporter) in the lung epithelium and innate immune cells in the context of cigarette smoking-related lung disease and lung fibrosis. We want to better understand how, in health and disease, ANT regulates epithelial and macrophage function through mitochondrial metabolism and cellular senescence. We have also found that ANT plays a role in airway epithelial homeostasis through surface hydration and the action of tiny motile cilia in the airway. We utilize a repertoire of relevant murine models of injury, molecular genetic approaches, in vitro biochemical assays, and human bio-samples to examine mitochondrial and cell homeostasis in the lung.

Three important hallmarks of lung aging are mitochondrial dysfunction, reduced repair after injury and senescence.  Two notable lung diseases characterized by accelerated aging include chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), with no current curative therapies. We have further linked reductions in ANT expression in human COPD and IPF lung tissue with mitochondrial dysfunction leading to reduced epithelial cell reparative capacity and increased senescence. The specific roles of mitochondrial dysfunction in lung aging at the molecular, cellular and tissue levels remain major knowledge gaps, offering opportunity for therapeutic manipulation to optimize epithelial repair and prevent disease. Our research program extends from model organisms to cutting edge 3D human tissue models (alveolar organoids and precision cut lung slices) which uniquely positions us to determine the mechanisms driving lung aging in COPD and IPF to identify new therapies.  Our program has three components that focus on mitochondrial dysfunction in COPD and IPF: 1) alveolar epithelial repair, 2) cellular quiescence versus senescence, and 3) therapeutic optimization of mitochondria and reduction in senescence to protect against accelerated aging in disease.