Dr Christine Pullar
| Tel: 0116 229 7139 Email: cp161@le.ac.uk |
Research Interests and Techniques
The Role of the ß2-AR and Wound Electric Fields in Wound Healing
Angiogenesis is essential for wound repair. Impaired blood vessel growth or permeability correlates with delayed healing. Endothelial cells are guided into the wound bed, where they align to form new blood vessels to supply the regenerating tissue with nutrients.
The guidance systems that play a role in wound angiogenesis are unknown. ß2-adrenoceptors (ß2-ARs) are G-protein-coupled receptors for catecholamines that couple to Gαs, increasing intracellular cAMP. Previous work shows that ß2-ARs regulate electric field-mediated directional migration (galvanotaxis) and wound repair, conceivably via cAMP-dependent and independent mechanisms (1-9). ß2-ARs and endogenous electric fields could be hitherto unrecognised regulators of wound angiogenesis.
A number of cell physiology, cell biology, time-lapse and fluorescence imaging techniques, including FRET, will be used to study mechanisms of endothelial cell galvanotaxis and the role that ß2-ARs and electric guidance cues play in angiogenesis and wound repair. Increasing our knowledge of systems that regulate angiogenesis and wound repair will pave the way for the development of new treatments (both pharmacological and electric) to improve wound healing.
Research Group and Funding
Andrew O'Leary
Dr Gabrielle Le Provost
Recent Publications
Sivamani RK, Pullar CE, Manabat-Hidalgo CG, Rocke DM, Carlsen RC, Greenhalgh DC and Isserroff RR. (2009) Stress mediated increases in systemic and local epinephrine impair skin wound healing: potential new indication for beta blockers. PLoS Medicine, 6(1) e12
Pullar CE, Manabat-Hidalgo CG, Bolaji RS and Isserroff RR. (2008) ß-Adrenergic Receptor modulation of wound repair. Pharmacological Research 58(2) 158-64
Ghoghawala SY, Mannis MJ, Pullar CE, Rosenblatt MI, Isseroff RR (2008) ß2-Adrenergic Receptor Signaling mediates corneal epithelial wound repair. Journal of Investigative Ophthalmology and Visual Science 49(5):1857-63
Pullar CE, Zhao M, Song B, Pu J, Reid B, Ghoghawala S, McCaig C and Isseroff RR. (2007) Beta-adrenergic receptor agonists delay while antagonists accelerate epithelial wound healing: evidence of an endogenous adrenergic network within the corneal epithelium. J Cell Physiol 211, 261-272
Pullar CE, Baier BS, Kariya Y, Russell AJ, Horst BA, Marinkovich MP and Isseroff RR. (2006) beta4 integrin and epidermal growth factor coordinately regulate electric field-mediated directional migration via Rac1. Mol Biol Cell 17, 4925-4935
Pullar CE, Grahn JC, Liu W and Isseroff RR. (2006) Beta2-adrenergic receptor activation delays wound healing. Faseb J 20, 76-86
Pullar CE and Isseroff RR. (2006) The beta 2-adrenergic receptor activates pro-migratory and pro-proliferative pathways in dermal fibroblasts via divergent mechanisms. J Cell Sci 119, 592-602
Pullar CE, Rizzo A and Isseroff RR. (2006) beta-Adrenergic receptor antagonists accelerate skin wound healing: evidence for a catecholamine synthesis network in the epidermis. J Biol Chem 281, 21225-21235
Pullar CE and Isseroff RR. (2005) Beta 2-adrenergic receptor activation delays dermal fibroblast-mediated contraction of collagen gels via a cAMP-dependent mechanism. Wound Repair Regen 13, 405-411
Pullar CE and Isseroff RR. (2005) Cyclic AMP mediates keratinocyte directional migration in an electric field. J Cell Sci 118, 2023-2034
Pullar CE, Chen J and Isseroff RR. (2003) PP2A activation by beta2-adrenergic receptor agonists: novel regulatory mechanism of keratinocyte migration. J Biol Chem 278, 22555-22562
Pullar CE, Isseroff RR and Nuccitelli R. (2001) Cyclic AMP-dependent protein kinase A plays a role in the directed migration of human keratinocytes in a DC electric field. Cell Motil Cytoskeleton 50, 207-217
