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Faculty Detail Faculty Entry   
Name JUDY CREIGHTON  
Campus Address BMR2 326 Zip 2180
Phone 205-934-7707
E-mail jcreighton@uab.edu" id="FacultyDetail1EmailAddress"><a href="mailto:jcreighton@uab.edu">jcreighton@uab.edu</a>
URL
 
 

Department Affiliations(s)
Appointment Type Department Division Rank
Center  General Clinical Research Center  Ctr for Clinical & Translational Sci Assistant Professor
Primary  Anesthesiology   Anesthesiology Chair Office Assistant Professor

Biographical Sketch 
Dr. Creighton graduated from the University of South Alabama in 2006. Her early research work involved the study of lung capillary endothelial cells. She used these cells to identify a signaling pathway (phosphodiesterase 4D4) important in maintaining the blood tissue barrier. This work also contributed to the understanding that there is phenotypic and functional heterogeneity inherit in endothelium derived from different vascular segments.

She spent her post doctoral experience with Paul Insel from the University of California at San Diego, where she developed an independent project that formed the basis for an NIH sponsored RO1. She found that Adenosine Monophosphate-activated Kinase (AMPK), an enzyme critical for metabolic sensing and homeostatic maintenance, also functions as a repair mechanism in the lung. This novel observation has broad clinical relevance. Impaired AMPK function is associated with hypertension, diabetes, and metabolic syndrome; diseases that have major impacts on human health. Importantly, simvastatin, metformin, metoprolol, and albuterol which are already approved for use in humans have a potentially therapeutic “side effect”, they activate AMPK. Thus, her work suggests new use applications for these drugs as treatments in lung vascular disease.

Society Memberships
Organization Name Position Held Org Link
American Journal of Physiology   Reviewer  http://www.physiology.org 
American Physiological Society  Member  http://www.the-aps.org 
American Association for the Advancement of Science  Member  http://www.aaas.org 
American Journal of Physiology  Contributing Editor  http://www.physiology.org 
American Journal of Respiratory Cell and Molecular Biology  Reviewer  http://ajrcmb.atsjournals.org 
American Thoracic Society  Member  http://www.thoracic.org 
Mechanisms of Ageing and Development  Reviewer  www.journals.elsevier.com/mechanisms-of-ageing-and-development 
Physiological Research  Reviewer  http://www.biomed.cas.cz/physiolres 
Pulmonary Pharmacology and Therapeutics  Reviewer  http://www.sciencedirect.com/science/journal/10945539 
Society for Experimental Biology and Medicine  Member  http://www.sebm.org 
 

Research/Clinical Interest
Title
AMPK activates calcium signaling necessary for endothelial barrier repair.
Description
Subspecialties and Areas of Interest: Lung Vascular Injury and Repair, Diagnosis of vascular disease,Vascular cell pathophysiology, Effects of chlorine injury on lung endothelium,Sepsis, Acute Respiratory Distress Syndrome (ARDS), Asthma, Endothelial phenotypes, Endothelial cell dysfunction, Endothelial cell heterogeneity, Metabolic Sensing in the lung, Cellular homeostatic mechanisms, Metabolic syndrome,and Effects of diabetes on the pulmonary vasculature.

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 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 AMPK alpha1 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 and 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.

Postdoc Positions Available
Date Posted Position Title
No records
 

Selected Publications 
Publication PUBMEDID
Creighton J. Targeting therapeutic effects: sub-cellular location matters. Focus on “Pharmacological AMP-kinase activators have compartment-specific effects on cell physiology” Am J Physiol Cell Physiol., 2011 .Sep 28. [Epub ahead of print]   21956167 
Stevens T, Creighton J, and Thompson, WJ. Control of cAMP in lung endothelial cell phenotypes. Implications for control of barrier function. Am. J. Physiol., 277 (1 Pt 1), L119-26, 1999.   10409238 
Norwood N, Moore T, Dean D, Bhattacharjee R, Creighton J, Babal P, and Stevens T. Store operated Ca2+ entry and endothelial cell permeability. Am. J. Physiol Lung Cell Mol Physiol., 279: L815-L824, 2000.

 		 11053015 
Moore T, Norwood N, Creighton J, Babal P, Brough G, Shasby D, and Stevens T. Receptor dependent activation of store-operated Ca2+ entry increases endothelial cell permeability. Am. J. Physiol., 279: L691-L698, 2000.

 
 		 11000129 
Cioffi DL, Moore TM, Schaack J, Creighton JR, Cooper DM, and Stevens T. Dominant regulation of interendothelial cell gap formation by calcium inhibited type 6 adenylyl cyclase. J. Cell Biol. 157 (7):1267-78, 2002  12082084 
Creighton J, Masada N, Cooper DMF, and Stevens T. Coordinate regulation of membrane cAMP by Ca2+-inhibited adenylyl cyclase and phosphodiesterase activities. Am. J. Physiol Lung Cell Mol Physiol., 284 (1): L100-7, 2003.




 		 12471013 
King J, Hamil T, Creighton J, Wu S, Bhat P, McDonald F, and Stevens T. Structural and functional characteristics of lung macro- and microvascular endothelial cell phenotypes. Microvasc. Research, 67: 139-151, 2004.
 		 15020205 
Wu S, Cioffi E, Alvarez D, Sayner S, Chen H, Cioffi D, King J, Creighton J, Townsley M, Goodman S, and Stevens T. Essential role of a Ca2+ selective, store operated current (ISOC) in endothelial cell permeability. Determinants of the vascular leak site. Circ Res. 96:856-863, 2005.


 		 15790951 
Creighton J, Zhu B, Alexyev M, and Stevens T. Spectrin-anchored phosphodiesterase 4D4 restricts cAMP from disrupting microtubules and inducing endothelial cell gap formation. J Cell Sci. 121 (Pt 1):110-9, 2008.


 		 18073242 
Zhu B, Creighton J, and Stevens T. Protein kinase A phosphorylation of Tau-serine 214 reorganizes microtubules and disrupts the endothelial cell barrier Accepted: Am. J. Physiol Lung Cell Mol Physiol. 2010 Oct;299(4):L493-501. Epub 2010 Jul 16.

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Keywords
lung, endothelium, calcium signaling, permeability, capillary, microvascular

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