EDUCATIONAL HISTORY

HONORS AND AWARDS

1994 Outstanding Scholar, University of West Florida

1994 Member Phi Kappa Phi Honor Society
  

RESEARCH AND PROFESSIONAL EXPERIENCE

1998-2002

Research Technologist, Department of 

Pharmacology, University of South Alabama

RESEARCH FUNDING

American Heart Association predoctoral fellowship recipient 

As part of the Center for Lung Biology at the University of South Alabama, my research interests are focused on mechanisms of lung disease related to the pulmonary vasculature. Historically, drug design has been based on the belief that all pulmonary endothelium responded to therapeutic intervention in the same manner. This premise originated from studies using endothelial cells obtained from the pulmonary artery (PAECs). Later studies utilizing pulmonary microvascular (capillary) endothelial cells (PMVECs) demonstrated that pulmonary endothelium displayed distinct functional heterogeneity. Principal among the functional differences in lung endothelium is relative barrier permeability. PMVECs form a tighter more restrictive barrier to blood fluids than do PAECs. In vivo and in vitro studies, indicate the second messengers adenosine 3’, 5’ cyclic monophosphate (cAMP) and cytosolic calcium ([Ca²⁺]_i) are important in the regulation of endothelial barrier integrity. Increases in cAMP tend to be barrier protective, whereas, increases in [Ca²⁺]_i tend to be barrier disruptive. Therefore, physiologic/pathologic mechanisms that increase [Ca²⁺]_i and decrease cAMP contribute to edema-associated pulmonary distress. In pulmonary endothelium, cAMP represents a balance between activities of calcium-inhibited adenylyl cyclase (AC₆) that converts ATP-to-cAMP and type 4 phosphodiesterases (PDE4) that hydrolyze cAMP-to-5’AMP. My studies suggest these signaling molecules are grouped differently in the two endothelial cell types, thus allowing cell specific cAMP responses to the same stimulus (drug). Understanding these functional differences in lung endothelium will ultimately lead to improved drug design and more effective therapy for treating pulmonary vascular disease.

PUBLICATIONS

1. 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. 

2. 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.

3. 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., 279: L815-L824, 2000.

4. 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. 

5. 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. 284 (1): L100-7, 2003. 

6. 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. Microvascular Research, 67: 139-151, 2004.

7. Wu S, Cioffi E, Sayner S, King J, Cioffi D, Creighton J, Goodman S, and Stevens T. Selective disruption of endothelial cell adhesion by activation of a Ca²⁺ selective store-operated current, I_SOC. In preparation.

8. Creighton J, Zhu B, Alexeyev M, and Stevens T. Spectrin-anchored Phosphodiesterase 4D4 Restricts cAMP to Barrier Enhancing Membrane Domains in Endothelium. In submission.

ABSTRACTS

1. Creighton J, Thompson WJ, and Stevens T. Regulation of cAMP in lung micro-and macrovascular endothelial cells: Mechanisms of enhanced barrier function. FASEB J., 13: A488, 1999.

2. Norwood N, Moore T, Creighton J, Babal P, Bhattacharjee R, and Stevens T. Myosin light chain kinase regulates activation of store-operated calcium entry in pulmonary artery endothelial cells. FASEB J., 13: A502, 1999.

3. Norwood N, Dean D, Moore T, Creighton J, Babal P, and Stevens T. Inhibition of myosin light chain kinase stimulates Ca²⁺ release in pulmonary artery endothelial cells. FASEB J., 13: A503, 1999.

4. Moore T, Norwood N, Creighton J, Babal P, Brough G, and Stevens T. Calcium influx is sufficient but not required for thrombin-induced endothelial cell shape change. FASEB J., 13: A501, 1999.

5. Creighton J, and Stevens T. cAMP accumulation dictates Ca²⁺ inhibition of adenylyl cyclase 6 necessary to increase gap formation in lung microvascular endothelial cells. FASEB J., 14: A693, 2000.

6. Wu S, Brough G, Creighton J, El-Menshawi M, Goodman S, and Stevens T. Disruption of F-actin binding to non-erythroid spectrin induces focal inter-endothelial cell gaps. FASEB J., 14: A694, 2000.

7. Creighton J, and Stevens T. Ca²⁺ inhibition of adenylyl cyclase 6 is regulated by cAMP in lung microvascular endothelial cells. FASEB J., 15: A161, 2001.

8. King J, Weathington T, Creighton J, McDonald F, Gillespie MN, Olson J, Parker J, and Stevens T. Characterization of phenotypically distinct endothelial cell populations from rat lung. FASEB J., 15: A492, 2001. 

9. Cioffi D, Creighton J, Cananles K, Cooper DMF, and Stevens T. Expression of a calcium-stimulated adenylyl cyclase prevents thrombin-induced gap formation in microvascular endothelium. FASEB J., 15: A160, 2001.

10. Wu S, Creighton J, King J, and Stevens T. Selective disruption of endothelial cell adhesion by activation of a Ca²⁺ selective store-operated current, ISOC. FASEB J., 2002.

11. Creighton J, Zhu B, and Stevens T. Functional co-localization of calcium-inhibited adenylyl cyclase and type 4 phosphodiesterase to caveolin-enriched regions controls membrane-associated camp concentrations in lung microvascular endothelium. FASEB J., 18 (4) : A716, 2004.

12. Creighton J, Zhu B, and Stevens T. Cyclic AMP phosphodiesterase and non-erythroid spectrin interact at regions of cell-cell contact in lung microvascular endothelium FASEB J., 19 (5):A1274, 2005.

13. Creighton J, Zhu B, Alexeyev M, and Stevens T. Cyclic AMP Phosphodiesterase 4D4 Activity Critically Maintains Membrane cAMP in Lung Microvascular Endothelium. FASEB J., 20 (4): A748, 2006.

14.Chen H, Chou C, Creighton J, Sellak H, Wu S. Regulation of Cav3.1 T- type calcium channel expression by cAMP in pulmonary microvascular endothelial cells. FASEB J., 20 (4) A749, 2006.

15. Zhu B, Creighton J, Stevens T. Association of cAMP phosphodiesterase with microtubule binding proteins in pulmonary endothelium: the PKA-mediated phosphorylation of Tau and MAP4. FASEB J. 20 (4) A1164, 2006

16.Creighton J, Zhu B, Alexeyev M, Stevens T. Cyclic AMP phosphodiesterase 4D4 expression in lung endothelium is a determinant of cell phenotype. FASEB J. 21 (6) A1433, 2007.

17.Creighton J, Stevens T, Insel P. Adenosine monophosphate kinase (AMPK) expression in the normoxic and hypoxic lung. FASEB J. 21 (6) A1436, 2007.

PRESENTATIONS

Abstract selected for special topics presentation by the respiration section of the American Physiological Society at Experimental Biology 1999.

UNIVERSITY SERVICE

Last update: Oct. 02, 2006