Creighton Lab

Creighton_JudyWebThe 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, is 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 lab has shown 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 pulmonary microvascular endothelial cells (PMVECs) to re-establish tight cell-cell adhesions quickly and limit increased capillary permeability.  Our work supports the idea of endothelial biomedicine with the goal of developing therapeutic strategies targeted toward vascular bed specific disease.

Current Projects

  • Function of AMPK relative to tissue specific expression and sub-cellular localization.
  • Metabolic mechanisms controlling endothelial permeability
    Heterogeneity of endothelial cell-cell adhesions: cadherin expression and adherens junction composition
  • Calcium channel regulation by vascular protective mechanisms in pulmonary endothelium
  • Endothelial phenotype specific response to stimuli