Professor Christine Pullar

Tel: +44 (0)116 229 7139
Email: cp161@le.ac.uk

Personal details

  • PhD: Cell and Molecular Biology, the Department of Molecular Biology and Biotechnology, University of Sheffield, UK 1994
  • Research Assistant, University of Sheffield, 1993-1994
  • Post-Doc, Hoffman La Roche, NJ, USA 1994-1997
  • Post-Doc, University of Oxford, 1997-1999
  • Senior R&D Scientist, Surgica Corporation, CA, USA 1999-2000
  • Post-Doc, University of California Davis, 2001-2003
  • Assistant Researcher, University of California Davis, 2003-2006
  • Lecturer, University of Leicester, 2006-2011
  • Senior Lecturer, University of Leicester, 2011-2016
  • Professor of Cell Biology and Regenerative Medicine, University of Leicester, 2016-present

Publications

Articles

23. Riding A and Pullar CE. ATP release and P2Y Receptor Signalling are Essential for Keratinocyte Galvanotaxis. J Cell Physiol. 2016 J Cell Physiol.  Jan;231(1):181-91.

22. Ud-Din, S, Seban, A, Giddings, P, Colthurst, J, Whiteside, S, Morris, J, Nuccitelli, R, Pullar, CE, Baguneid, M and Bayat A. Angiogenesis is induced and wound size is reduced by electrical stimulation in an acute wound healing model in human skin. PLoS One. 2015. 2015 Apr 30;10(4):e0124502

21. Martin, KJ, Muessel MJ, Pullar CE, Willars GB, Wardlaw AJ. The role of phosphoinositide 3-kinases in neutrophil migration in 3D collagen gels. PLoS One. 2015. Feb 6;10(2):e0116250.

20. Le Provost GS, Pullar CE. β2-Adrenoceptor Activation Modulates Skin Wound Healing Processes to Reduce Scarring. JID. Jul 22. PMID: 25050597. 2014.

19. O'Leary AP, Fox JM, Pullar CE. Beta-Adrenoceptor Activation Reduces Both Dermal Microvascular Endothelial Cell Migration Via a cAMP-Dependent Mechanism and Wound Angiogenesis. J Cell Physiol. Jul 1. PMID: 24986762. 2014.

18. Pier DM, Shehatou GS, Giblett S, Pullar CE, Trezise DJ, Pritchard CA, Challiss RA, Mitcheson JS. Long-term channel block is required to inhibit cellular transformation by human ether-à-go-go-related gene (hERG1) potassium channels. Mol Pharmacol. Aug; 86(2):211-21. 2014.

17. Hart FX, Laird M, Riding A, Pullar CE. Keratinocyte galvanotaxis in combined DC and AC electric fields supports an electromechanical transduction sensing mechanism. Bioelectromagnetics. 34(2): 85-94. 2013.

16. Abdallah Hajj Hussein, N. Dali Balta, R. A. Jurjus, W. Watfa, A. Gerges, B. Atiyeh, C. Pullar, A. Leone and A. R. Jurjus. Rat model of burn wound healing: Effect of Botox. Accepted by Biological Regulators and Homeostatic agents. 26(3):389-400. 2012.

15. Christine E. Pullar, Gabrielle S. Le Provost, Andrew P. O’Leary, Sian E. Evans, Brian S. Baier and R. Rivkah Isseroff. β2AR antagonists and β2AR gene deletion both promote skin wound repair processes. Journal of Investigative Dermatology. 32(8):2076-84. 2012.

14. K. Clark, J.D. Howe, C.E. Pullar, J.A. Green, V. Artym, K.M. Yamada and D.R. Critchley Tensin 2 modulates cell contractility through the DLC1 RhoGAP. Journal of Cellular Biochemistry. 109(4): 808-17. 2010.

13. Angelo Bella, Jennifer Phu, Andrew Bottrill, Sharad Mistry, Christine E. Pullar and Maxin G Ryadnov. Conformationally constrained mimetics of laminin peptide YIGSR as precursors for antimetastatic disintegrins. Journal of Medicinal Chemistry 52(24) 7966-9. 2009.

12. Christine E. Pullar. The biological basis for electrical stimulation as a therapy to heal chronic wounds. Journal of Wound Technology October vol 6: 20-24. 2009.

11. Raja K. Sivamani, Christine E. Pullar, Catherine G. Manabat-Hidalgo, David M. Rocke, Richard C. Carlsen, David G. Greenhalgh and R. Rivkah Isserroff. Stress mediated increases in systemic and local epinephrine impair skin wound healing: potential new indication for beta blockers. PLoS Medicine. Jan 13;6(1):e12. 2009.

10. Christine E. Pullar, Catherine G. Manabat-Hidalgo, Ranti S. Bolaji and R. Rivkah Isseroff. ß-Adrenergic Receptor modulation of wound repair. Pharmacological Research, 58(2) 158-64. 2008.

9. Ghoghawala SY, Mannis MJ, Pullar CE, Rosenblatt MI and Isseroff RR. ß-Adrenergic Receptor signaling mediates corneal epithelial wound repair. Journal of Investigative Ophthalmology and Visual Science. 49(5): 1857-63. 2008.

8. Christine E. Pullar, Min Zhao, Bing Song, Jin Pu, Brian Reid, Shahed Goghwala, Colin McCaig & R. Rivkah Isseroff. ß-AR agonists delay and antagonists accelerate corneal wound healing: Evidence for a novel catecholamine regulatory network in the cornea. Journal of Cellular Physiology. 211(1): 261-272. 2007.

7. Christine E. Pullar, Amilcar Rizzo & R. Rivkah Isseroff. ß-AR antagonists accelerate skin wound healing: Evidence for a catecholamine synthesis network in the epidermis. Journal of Biological Chemistry. 281:21225-35. 2006.

6. Christine. E. Pullar & R. Rivkah Isseroff. ß2-adrenergic receptor activates pro-migratory and pro proliferative pathways in dermal fibroblasts via divergent mechanisms. Journal of Cell Science. 119: 592-602. 2006.

5. Christine E. Pullar, Jennifer C. Grahn, Wei Liu & R. Rivkah Isseroff. ß2-adrenergic receptor activation delays wound healing. FASEBJ, 20: 76-86. 2006.

4. Pullar CE, Baier BS, Kariya Y, Russel AJ, Horst BA, Marinkovich MP and Isseroff RR. ß4 Integrin and EGF coordinately regulate electric field-mediated directional migration via rac1. Molecular Biology of the Cell 17(11): 4925-4935. 2006.

3. Christine. E. Pullar & R. Rivkah Isseroff. ß2-adrenergic receptor activation attenuates dermal fibroblast-mediated contraction of  collagen gels via a cAMP-mediated mechanism. Wound Repair and Regeneration. 13: 405-411. 2005.

2. Christine E. Pullar,  & R. Rivkah Isseroff. Cyclic AMP mediates keratinocyte directional migration in an electric field. Journal of Cell Science 118: 2023-2034. 2005.

1. Christine. E. Pullar, Jin Chen & R. Rivkah Isseroff. PP2A activation by ß2-adrenergic receptor agonists: Novel regulatory mechanism of keratinocyte migration. Journal of Biological Chemistry. 278: 22555-22562, 2003.

Books

Editor of a Taylor and Francis book entitled “The physiology of bioelectricity in development, tissue regeneration and cancer” due to be published by CRC Press, March 2011. “Keratinocyte galvanotaxis” by Christine E. Pullar. Chapter 6. “Immune cell galvanotaxis” by Francis Lin and Christine E. Pullar. Chapter 8.

Research

I study the roles of the ß2-adrenoceptor and endogenous cues in skin wound repair and scarring and delineate the underpinning mechanisms which promote tissue regeneration over fibrosis. The physiological processes of inflammation, re-epithelialisation, angiogenesis, dermal remodelling and scarring are studied in detail using a range of in vitro, ex-vivo and in vivo models.

Wound healing and scarring

Wound healing is a complex process requiring the coordinated, temporal orchestration of numerous cell types and processes to initiate repair. Evolution has augmented wound-healing responses to ensure quick restoration of the epidermal barrier and rapid wound closure, but with the consequence that adults wounds always heal with a scar. Any disruption to the wound healing process such as excessive or prolonged inflammation or an underlying pathophysiology can result in a chronic wound. The Pullar lab investigates the mechanisms of wound repair to identify treatment options to promote healing in chronic wounds and reduce wound scarring.

Chronic wounds

Chronic skin ulcers are non-healing wounds accompanied by impaired dermal fibroblast and keratinocyte function, chronic inflammation and reduced angiogenesis. Illnesses that compromise skin repair, such as diabetes and peripheral vascular disease, are increasingly common and it is estimated that the prevalence of patients with at least one chronic wound is 200,000 per year in the UK and 8 million per year in the USA. The associated health care costs account for 3% of the total NHS health-care budget. Elderly and disabled people are particularly at risk from chronic ulcers.

Scars

One hundred million patients in the developed world heal with a scar every year as a result of elective procedures, trauma and burn injuries, causing serious cosmetic and functional problems that can be emotionally and physically debilitating. This is especially true for patients with darker skin tones who often suffer disfiguring hyperpigmentation making any skin injury especially traumatic.  Scars place a heavy financial burden on health care systems worldwide.

Christine Pullar - Research Page Image 1

Beta-adrenergic receptors

The epidermis can synthesise and secrete a number of proteins including epinephrine, a ligand for the Beta-adrenergic receptors (bARs): b1AR; b2AR and b3AR. They are G protein-coupled receptors highly expressed on all cell lineages in skin, therefore, an autocrine and paracrine bAR network exists in the epidermis and dermis, respectively (7).

Previous and current work in the Pullar lab demonstrates the potential of both b2AR antagonism to promote healing in chronic wounds and b2AR agonism to reduce the excessive cell behaviour that contributes to scarring (1, 3, 5-11, 15).

b2AR antagonism and chronic wounds

b2AR antagonism increased angiogenesis, dermal fibroblast function and re-epithelialization, while having no effect on wound inflammation in vivo. Skin wounds in b2AR knockout mice contracted and re-epithelialized faster in the first few days of wound repair in vivo (15).

b2AR agonists and scars

An effective anti-scarring treatment would not only benefit the millions of patients with skin trauma and hypertrophic scarring, but could reduce keloid formation and fibrosis in other tissues and organs. There are currently no clinically proven small molecule interventions or pharmaceuticals available to prevent/reduce wound fibrosis and scarring. Due to the sheer complexity of wound repair, multiple cell types and cellular processes will need to be targeted to shift the balance of healing away from scarring and towards tissue regeneration. Current work demonstrates that b2AR agonist treatment, at the time of wounding, reduces inflammation, angiogenesis and curbs dermal fibroblast function, ultimately significantly reducing scar formation (19,20). An MRC Biomedical Catalyst grant is supporting formulation development and pre-clinical safety and efficacy studies to commence a scar prevention clinical trial to test safety and efficacy of the formulation in human healthy volunteers.

Electric fields and chronic wounds

The first wound cue to indicate that damage has occurred is electrical in nature. A direct current (DC) electrical wound guidance cue is generated, immediately, with the cathode of the electric field (EF) located at the centre of the wound. This physiological, electrical signal can be measured in acute skin wounds and is generally between 100-150mV/mm, but is reduced by 50% in elderly patients. Research over three decades has demonstrated that these endogenous EFs are essential cues during embryonic development and regenerative repair. Many wounds in our aging population fail to heal are extremely physically and emotionally debilitating and place heavy financial burden on health care systems worldwide. EF application (e.g. WoundEl – pulsed current (PC) EF) is now a mainstream healthcare option for persistent non-closing wounds in the US, and has the highest level of evidence for healing chronic recalcitrant wounds in Europe. We believe that the endogenous EF is the first signal that cells receive to indicate that damage has occurred and to promote cell behaviour to close the wound (B1, 2, 4, 12, 17, 23). A Molnlycke-funded collaborative research project has revealed the complex gene/protein alterations that the WoundEl device PC EF creates in all cell types involved in wound repair.

Processes studied in the lab:

Cell: migration (1, 6, 14, 21, 23); proliferation (6, 7); differentiation; directional cell migration-galvanotaxis (B1, 2, 4, 12, 17); growth factor secretion; gene and protein expression changes.

Skin wound: Inflammation (15, 20); angiogenesis (15, 19, 20); re-epithelialisation (5, 7, 11, 15, 20); dermal fibroblast function (3, 6, 15, 20); healing (5, 7, 10, 11, 15, 16, 20, 22); scarring (19, 20). Corneal wound repair (8, 9).

Techniques

A number of cell physiology, cell biology, molecular biology, time-lapse and fluorescence imaging techniques, will be used to study the mechanisms by which ß2-ARs and electric guidance cues modulate wound repair. Complex models are used to study wound repair processes. Increasing our knowledge of systems that regulate wound repair will pave the way for the development of new treatments (both pharmacological and electric) to improve wound healing and reduce scarring.

Research funding

The lab has received funding from The Wellcome Trust, MRC, British Skin Foundation, Medisearch and Molnlycke Healthcare.

Research Group

  • Waseem Ali (PhD student)
  • Karrar Kamoona (PhD student)
  • Zainab Al-Joubouri (PhD student)
  • Jill Theaker (Senior technician)

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Contact Details

Department of Molecular and Cell Biology
Henry Wellcome Building
Lancaster Road
Leicester
LE1 7RH (Postal)

LE1 7HB (Sat Nav/Online maps)

T:  +44(0)116 229 7038
F:  +44(0)116 229 7123
MolCellBiol@le.ac.uk

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Redfearn Lecture 2017

To Be Confirmed