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Prof David Becker

Research Summary

Wound healing 



We have shown that cell-cell communication through gap junctions plays a pivotal role in the wound healing process. In response to injury, the expression of different connexins is dynamically regulated at the transcriptional and translational level. We have found that actively down-regulating the gap junction protein Cx43, by applying an antisense gel to the wound, dramatically speeds up the process of wound healing whilst reducing inflammation and scarring. This patented approach is effective in promoting healing in a number of tissue injuries, from skin to cornea.


Diabetic wound healing is notoriously slow and often results in the formation of chronic wounds. We have found that in response to injury, the dynamic response of connexins in diabetic skin appears to be completely different from that of normal skin, with Cx43 turning on rather than off thereby generating different communication characteristics in the injured tissue. Preventing the abnormal turn on of Cx43 with out antisense gel restores healing rates to normal.  It also highlights connexin expression as a potential therapeutic target for diabetic wound healing.

Our Biotech company, CoDaTherapeutics is now developing this antisense which is performing well in Phase 2 clinical trials treating venous leg ulcers.

Research in the lab is investigating the roles of different connexins in chronic wound healing and fibrosis with the aim of understanding why these wounds fail to heal and searching for new therapeutic targets.



Research Activities

  • Axonal regeneration
  • Circadian rhythms. Light detection. Cell cycle timing.
  • Diabetic Autonomic Neuropathy
  • Functional adaptation of the musculoskeletal system and its application to Pathobiology of the skeleton
  • Gap junctions in development and disease
  • Role of gap junctions and regulatory proteins in the long-term maintenance of hearing.
  • Sensory cell death in the inner ear, repair of the sensory epithelia and protection and regeneration of hair cells
  • Signalling by the RAS family of oncogenes

Recent Publications

Displaying 50 most recent publications. For the full list please visit UCL Discovery

  1. Davis NG,Phillips A,Becker DL (2013) Connexin dynamics in the privileged wound healing of the buccal mucosa. Wound Repair Regen. 10.1111/wrr.12054.
  2. Gilmartin DJ,Alexaline MM,Thrasivoulou C,Phillips AR,Jayasinghe SN,Becker DL (2013) Integration of Scaffolds into Full-Thickness Skin Wounds: The Connexin Response. Adv Healthc Mater. 10.1002/adhm.201200357.
  3. Balasubramaniyan V,Dhar DK,Warner AE,Vivien Li WY,Amiri AF,Bright B,Mookerjee RP,Davies NA,Becker DL,Jalan R (2013) Importance of Connexin-43 based gap junction in cirrhosis and acute-on-chronic liver failure. J Hepatol. 10.1016/j.jhep.2013.01.023.
  4. Henderson LB,Patterson-Kane JC,Becker DL,Rich T (2012) The higher adaptive capacity of fibroblasts from injury-prone flexor tendons in cell culture: influence of matrix and oxygen tension INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, 93(4), A12 - A13.
  5. Wright JA,Richards T,Becker DL (2012) Connexins and diabetes. Cardiol Res Pract, 2012, 496904. 10.1155/2012/496904.
  6. Mendoza-Naranjo A,Cormie P,Serrano AE,Wang CM,Thrasivoulou C,Sutcliffe JE,Gilmartin DJ,Tsui J,Serena TE,Phillips AR,Becker DL (2012) Overexpression of the gap junction protein Cx43 as found in diabetic foot ulcers can retard fibroblast migration. Cell Biol Int, 36(7), 661 - 667. 10.1042/CBI20110628.
  7. Becker DL,Thrasivoulou C,Phillips AR (2012) Connexins in wound healing; perspectives in diabetic patients. Biochim Biophys Acta, 1818(8), 2068 - 2075. 10.1016/j.bbamem.2011.11.017.
  8. Mendoza-Naranjo A,Cormie P,Serrano AE,Hu R,O'Neill S,Wang CM,Thrasivoulou C,Power KT,White A,Serena T,Phillips AR,Becker DL (2012) Targeting Cx43 and N-cadherin, which are abnormally upregulated in venous leg ulcers, influences migration, adhesion and activation of Rho GTPases. PLoS One, 7(5), e37374. 10.1371/journal.pone.0037374.
  9. Patterson-Kane JC,Becker DL,Rich T (2012) The pathogenesis of tendon microdamage in athletes: the horse as a natural model for basic cellular research. J Comp Pathol, 147(2-3), 227 - 247. 10.1016/j.jcpa.2012.05.010.
  10. Vairappan B,Davies N,Mookerjee R,Becker DL,Warner A,Jalan R (2012) INFLAMMATION UPREGULATES HEPATIC CONNEXIN-43 EXPRESSION IN CIRRHOSIS WHICH DEFINES SUSCEPTIBILITY TO DEVELOPMENT OF ACUTE-ON CHRONIC LIVER FAILURE JOURNAL OF HEPATOLOGY, 56, S236 - S236.
  11. Mendoza-Naranjo A,Bouma G,Pereda C,Ramírez M,Webb KF,Tittarelli A,López MN,Kalergis AM,Thrasher AJ,Becker DL,Salazar-Onfray F (2011) Functional gap junctions accumulate at the immunological synapse and contribute to T cell activation. J Immunol, 187(6), 3121 - 3132. 10.4049/jimmunol.1100378.
  12. Chin KY,Sutcliffe JE,Serena TE,O'Neil S,Hu RG,White A,Phillips R,Becker DL (2011) ABNORMAL CONNEXIN43 EXPRESSION IN CHRONIC WOUNDS MAY PERTURB HEALING WOUND REPAIR REGEN, 19(2), A18 - A18.
  13. Thrasivoulou C,Virich G,Krenacs T,Korom I,Becker DL (2011) Optical delineation of human malignant melanoma using second harmonic imaging of collagen. Biomed Opt Express, 2(5), 1282 - 1295. 10.1364/BOE.2.001282.
  14. Dimitrakakis G,Thrasivoulou C,Lincoln J,Becker DL (2010) The downregulation of connexion-43 in wound healing process (40 days post injury). An experimental study BRITISH JOURNAL OF SURGERY, 97, S29 - S29.
  15. Cook JE,Becker DL (2009) Gap-junction proteins in retinal development: new roles for the "nexus". Physiology, 24(August), 219 - 230. 10.1152/physiol.00007.2009.
  16. Chang CY,Laux-Fenton WT,Law LY,Becker DL,Sherwin T,Green CR (2009) Antisense down regulation of connexin31.1 reduces apoptosis and increases thickness of human and animal corneal epithelia CELL BIOL INT, 33(3), 376 - 385. 10.1016/j.cellbi.2008.12.006.
  17. Waghabi MC,Coutinho-Silva R,Feige JJ,Higuchi MDEL,Becker D,Burnstock G,Araújo-Jorge TC (2009) Gap junction reduction in cardiomyocytes following transforming growth factor-beta treatment and Trypanosoma cruzi infection. Mem Inst Oswaldo Cruz, 104(8), 1083 - 1090.
  18. Young NJ,Becker DL,Fleck RA,Goodship AE,Patterson-Kane JC (2009) Maturational alterations in gap junction expression and associated collagen synthesis in response to tendon function MATRIX BIOL, 28(6), 311 - 323. 10.1016/j.matbio.2009.05.002.
  19. Cronin M,Anderson PN,Cook JE,Green CR,Becker DL (2008) Blocking connexin43 expression reduces inflammation and improves functional recovery after spinal cord injury Molecular and Cellular Neuroscience, 39(2), 152 - 160. 10.1016/j.mcn.2008.06.005.
  20. Lei Y,Garrahan N,Hermann B,Becker DL,Hernandez MR,Boulton ME,Morgan JE (2008) Quantification of retinal transneuronal degeneration in human glaucoma: a novel multiphoton-DAPI approach Investigative Ophthalmology and Visual Science, 49(5), 1940 - 1945. 10.1167/iovs.07-0735.
  21. Marina N,Becker DL,Gilbey MP (2008) Immunohistochemical detection of connexin36 in sympathetic preganglionic and somatic motoneurons in the adult rat Autonomic Neuroscience, 139(1-2), 15 - 23. 10.1016/j.autneu.2007.12.004.
  22. Tibber MS,Becker DL,Jeffery G (2007) Levels of transient gap junctions between the retinal pigment epithelium and the neuroblastic retina are influenced by catecholamines and correlate with patterns of cell production The Journal of Comparative Neurology, 503(1), 128 - 134.
  23. Valasek P,Macharia R,Neuhuber WL,Wilting J,Becker DL,Patel K (2007) Lymph heart in chick - somitic origin, development and embryonic oedema Development, 134(24), 4427 - 4436. 10.1242/dev.004697.
  24. Gorbe A,Krenacs T,Cook JE,Becker DL (2007) Myoblast proliferation and syncytial fusion both depend on connexin43 function in transfected skeletal muscle primary cultures Experimental Cell Research, 313(6), 1135 - 1148. 10.1016/j.yexcr.2007.01.012.
  25. Becker DL,Webb KF,Thrasivoulou C,Lin C-C,Nadershahi R,Tsakiri N,Cook JE (2007) Multiphoton imaging of chick retinal development in relation to gap junctional communication The Journal of Physiology, 585(3), 711 - 719. 10.1113/jphysiol.2007.138776.
  26. Wang CM,Green C,Duft BJ,Becker DL (2007) Targeting connexin43 expression accelerates the rate of skin and diabetic wound repair JOURNAL OF BIOTECHNOLOGY, 131(2), S64 - S64. 10.1016/j.jbiotec.2007.07.110.
  27. Stanley RL,Fleck RA,Becker DL,Goodship AE,Ralphs JR,Patterson-Kane JC (2007) Gap junction protein expression and cellularity: comparison of immature and adult equine digital tendons Journal of Anatomy, 211(3), 325 - 334. 10.1111/j.1469-7580.2007.00781.x.
  28. Wang CM,Lincoln J,Cook JE,Becker DL (2007) Abnormal connexin expression underlies delayed wound healing in diabetic skin Diabetes, 56(11), 2809 - 2817. 10.2337/db07-0613.
  29. Cronin M,Anderson P,Green CR,Becker DL (2006) Antisense delivery and protein knockdown within the intact central nervous system Frontiers in Bioscience, 11, 2967 - 2975.
  30. Nickel R,Becker D,Forge A (2006) Molecular and functional characterization of gap junctions in the avian inner ear Journal of Neuroscience, 26, 6190 - 6199. 10.1523/JNEUROSCI.1116-06.2006.
  31. Gorbe A,Becker DL,Dux L,Krenacs L,Krenacs T (2006) In differentiating prefusion myoblasts connexin43 gap junction coupling is upregulated before myoblast alignment then reduced in post-mitotic cells Histochemistry and Cell Biology, 125(6), 705 - 716.
  32. Law LY,Zhang W,Stott S,Becker DL,Green CR (2006) In vitro optimization of antisense oligodeoxynucleotide design: an example using the connexin gene family Journal of Biomolecular Techniques, 17(4), 270 - 282.
  33. Becker DL (2006) Treatment of chronic wounds with formulations comprising antisense nucleotides to connexins.
  34. Nickel R,Becker D,Forge A (2006) Molecular and functional characterization of gap junctions in the avian inner ear J NEUROSCI, 26(23), 6190 - 6199. 10.1523/KNEUROSCI.1116-06.2006.
  35. Wang M,Lincoln J,Becker D (2006) Gap junction expression in diabetic rat wound healing J ANAT, 209(4), 569 - 569.
  36. Mori R,Power K,Wang CM,Martin P,Becker DL (2006) Acute downregulation of connexin43 at wound sites leads to a reduced inflammatory response, enhanced keratinocyte proliferation and wound fibroblast migration Journal of Cell Science, 119(24), 5193 - 5203. 10.1242/jcs.03320.
  37. Becker DL,Thrasivoulou C (2006) Imaging method and apparatus. Multiphoton second harmonic imaging for defining the borders of skin cancers..
  38. Theodossiou TA,Thrasivoulou C,Ekwobi C,Becker DL (2006) Second harmonic generation confocal microscopy of collagen type I from rat tendon cryosections Biophysical Journal, 91(12), 4665 - 4677. 10.1529/biophysj.106.093740.
  39. Pearson RA,Luneborg NL,Becker DL,Mobbs P (2005) Gap junctions modulate interkinetic nuclear movement in retinal progenitor cells Journal of Neuroscience, 25(46), 10803 - 10814. 10.1523/JNEUROSCI.2312-05.2005.
  40. Pearson RA,Catsicas M,Becker D,Mobbs P (2005) A technique for the study of cell migration in the developing chick retina Society for Neuroscience Abstracts 780.5.
  41. Roberts R,Iatropoulou A,Ciantar D,Stark J,Becker DL,Franks S,Hardy K (2005) Follicle-Stimulating Hormone affects Metaphase 1 chromosome alignment and increases aneuploidy in mouse oocytes matured in vitro. Biology of Reproduction, 72, 107 - 118.
  42. Gorbe A,Becker DL,Dux L,Stelkovics E,Krenacs L,Bagdi E,Krenacs T (2005) Transient upregulation of connexin43 gap junctions and synchronized cell cycle control precede myoblast fusion in regenerating skeletal muscle in vivo Histochemistry and Cell Biology, 123, 573 - 583.
  43. Becker DL,Green CR (2005) Antisense compounds targeted to connexins and methods of use thereof.
  44. Coutinho P,Qiu C,Frank S,Wang CM,Brown T,Green CR,Becker DL (2005) Limiting burn extension by transient inhibition of Connexin43 expression at the site of injury British Journal of Plastic Surgery, 58, 658 - 667.
  45. Mori R,Becker DL,Martin P (2005) Modulating the inflammatory response at wound sites to improve the quality of healing JOURNAL OF LEUKOCYTE BIOLOGY, 69 - 70.
  46. Laux-Fenton WT,Chang C,McGhee CN,Grupcheva CN,Becker DL,Green CR (2004) Modulation of connexins for corneal tissue remodelling and engineering MOLECULAR BIOLOGY OF THE CELL, 15, 184A - 185A.
  47. Gorbe A,Becker DL,Dux L,Krenacs T (2004) Cx43 gap junction communication during muscle development JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 52, S49 - S49.
  48. Roberts R,Stark J,Iatropoulou A,Becker DL,Franks S,Hardy K (2004) Energy substrate metabolism of mouse cumulus-oocyte-complexes: response to follicle-stimulating hormone is mediated by the phosphatididylinositol 3-kinase pathway and associated with oocyte maturation Biology of Reproduction, 71, 199 - 209.
  49. Stilinovic A,Green CR,Klette R,Franke S,Klette G,Becker DL (2004) Texture analysis of collagen fibers in scar tissue Proceedings Image Vision Computing New Zealand 21 November 2004, P185 - 190.
  50. Saitongdee P,Becker DL,Milner P,Knight GE,Burnstock G (2004) Levels of gap junction proteins in coronary arterioles and aorta of hamsters exposed to the cold and during hibernation and arousal Journal of Histochemistry and Cytochemistry, 52(5), 603 - 615.

Qualifications

  • 1988: Doctor of Philosophy, University College London
  • 1985: Bachelor of Science (Honours), Portsmouth Polytechnic

Keywords

  • Anti-sense and morpholino approaches
  • Asymmetric cell division
  • CNS
  • Calcium
  • Calcium imaging
  • Cell culture
  • Cell tracking
  • Confocal microscopy
  • Connectivity
  • Development
  • Diabetes
  • Fluorescence Resonance Energy Transfer (FRET)
  • Fluorescence microscopy techniques
  • Genetic manipulation (including knockout/knockin)
  • Histology
  • Image analysis
  • Immunohistochemistry
  • Inflammation
  • Light microscopic techniques
  • Multi-photon imaging
  • Neural stem cells
  • Neuroblast
  • Neurogenesis
  • Neuroimaging
  • Not clinically oriented research
  • Optical imaging
  • Progenitors
  • Proliferation
  • Retina
  • Spinal cord
  • Spinal cord injury
  • Stem cells
  • Time-lapse imaging
  • Tissue repair and regeneration
  • Transgenic mice
  • Viral vectors
  • development