The Creighton Lab is led by Assistant Professor Judy R. Creighton, Ph.D.
Our research focuses on the discovery of endogenous repair mechanisms situated in the lung’s vascular lining, the endothelium. Although this thin layer of cells lines all vascular beds, not all endothelial cells are the same. Endothelium from various organs, and even from different vascular beds within the same organ, are physically and functionally distinct. We aim to understand how endothelium lining specific vascular segments within the lung contributes to overall lung health and to vascular repair following injury or disease. We find that the enzyme Adenosine Monophosphate Kinase (AMPK), classically described as a metabolic sensor, functions as an injury response mechanism in the lung’s capillary bed. Interestingly, our data show that AMPK promotes calcium signaling necessary for endothelial barrier repair. Calcium signaling is often associated with disruption of the endothelial lining. However, our work shows that AMPK activates a discrete calcium mechanism, which reorganizes the cytoskeleton crucial for cadherin adherens’ junction assembly and endothelial cell-cell adhesion. Specifically, our research tests the hypothesis that AMPKα1 and N-cadherin function in tandem as a rapid response mechanism allowing the lung’s capillary endothelium to re-establish tight cell-cell adhesions quickly and limit increased permeability. Our work supports the idea of endothelial biomedicine with the goal of developing therapeutic strategies targeted toward segment specific vascular disease.
- Function of AMPK relative to sub-cellular localization and tissue specific expression.
- Metabolic mechanisms controlling endothelial permeability.
- Endothelial cell-cell adhesion: cadherin expression and adherens junction composition.
- Calcium channel regulation by vascular protective mechanisms in pulmonary endothelium.
- Endothelial phenotype specific response to stimuli.
Areas of Interest
Lung vascular injury and repair
Cellular metabolic sensing and homeostatic mechanisms
Novel tools to diagnose vascular disease
Halogen injury in the lung
Acute Respiratory Distress Syndrome (ARDS)
Metabolic syndrome (including diabetes) with respect to its effects on the pulmonary vasculature.