Dr Gary Lawrence is Assistant Professor of Molecular Neurobiology in the School of Biotechnology at Dublin City University. His research interests are in functional neurobiology as it relates to human health, with a particular focus on the use of neurotoxins to elucidate nervous system function and as therapeutics for the treatment of a wide range of peripheral neuropathologies.
Gary has worked in Molecular Neurobiology for over 25 years. He studied for his doctorate degree at Imperial College London, where he investigated therole of SNAREs in the catalysis of Ca2+ regulated transmitterrelease from neuroendocrine cells. During a subsequent post-doctoral period in Imperial College he discovered that botulinum neurotoxin type C cleaves SNAP-25 as well as syntaxin, the first example of a botulinum protease cleaving more than one SNARE. Gary joined DCU as a Research Lecturer when Prof. Oliver Dolly established the International Centre for Neurotherapeutics in 2003, before entering the School of Biotechnology as an Assistant Professor in 2023. Gary continues to investigate the effects of botulinum neurotoxins on various divisions of the peripheral nervous system in vitro and in vivo, ranging from skeletal muscle motor neurons to sympathetic nerves, parasympathetic nerves, and the sensory neurons involved in sensation and pain. His research encompasses the effects of botulinum neurotoxins on diverse processes, including synaptic neurotransmission, neuropeptide exocytosis, membrane protein trafficking and axonal growth. Recent research and publications from the Lawrence group have focused on how transient receptor potential (TRP) channels encode pain-related signal intensity, and the role of membrane trafficking of TRP channels in the sensitisation of pain signalling nociceptor neurons by neurotrophins that are released at sites of injury, inflammation, or diseases such as cancer.
Book Chapter
| Year | Publication | |
|---|---|---|
| 2009 | Dolly, J.O.; Meng, J.; Wang, J.; Lawrence, G.W.; Bodeker, M.; Zurawski, T.H.; Sasse, A. (2009) 'Multiple steps in the blockade of exocytosis by botulinum neurotoxins' In: Botulinum Toxin: Therapeutic Clinical Practice and Science, Expert Consult - Online and Print. [Link] [DOI] |
Peer Reviewed Journal
| Year | Publication | |
|---|---|---|
| 2023 | Belinskaia, Mariia; Wang, Jiafu; Kaza, Seshu Kumar; Antoniazzi, Caren; Zurawski, Tomas; Dolly, J. Oliver; Lawrence, Gary W. (2023) 'Bipartite Activation of Sensory Neurons by a TRPA1 Agonist Allyl Isothiocyanate Is Reflected by Complex Ca2+ Influx and CGRP Release Patterns: Enhancement by NGF and Inhibition with VAMP and SNAP-25 Cleaving Botulinum Neurotoxins'. International Journal of Molecular Sciences, 24 (2). [DOI] | |
| 2023 | Corasaniti, M.T.; Lawrence, G.W.; Bagetta, G.; Iannacchero, R.; Tarsitano, A.; Monteleone, A.; Pagliaro, M.; Tonin, P.; Sandrini, G.; Nicotera, P.; Scuteri, D. (2023) 'Combination of anti-CGRP/CGRP-R mAbs with onabotulinumtoxin A as a novel therapeutic approach for refractory chronic migraine: a retrospective study of real-world clinical evidence and a protocol for a double-blind, randomized clinical trial to establish the efficacy and safety'. Frontiers in Pharmacology, 14 . [Link] [DOI] | |
| 2022 | Belinskaia, M.; Zurawski, T.; Kaza, S.K.; Antoniazzi, C.; Oliver Dolly, J.; Lawrence, G.W. (2022) 'NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases'. International Journal of Molecular Sciences, 23 . [Link] [DOI] | |
| 2021 | Antoniazzi, C; Belinskaia, M; Zurawski, T; Kaza, SK; Dolly, JO; Lawrence, GW (2021) 'Botulinum Neurotoxin Chimeras Suppress Stimulation by Capsaicin of Rat Trigeminal Sensory Neurons In Vivo and In Vitro'. Toxins, 14 (2). [DOI] | |
| 2021 | Lawrence, G.W.; Zurawski, T.H.; Dolly, J.O. (2021) 'Ca2+ signalling induced by ngf identifies a subset of capsaicin‐excitable neurons displaying enhanced chemo‐nociception in dorsal root ganglion explants from adult pirt‐gcamp3 mouse'. International Journal of Molecular Sciences, 22 . [Link] [DOI] | |
| 2021 | Lawrence, GW; Zurawski, TH; Dong, X; Dolly, JO (2021) 'Population Coding of Capsaicin Concentration by Sensory Neurons Revealed Using Ca2+ Imaging of Dorsal Root Ganglia Explants from Adult pirt-GCaMP3 Mouse'. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 55 (4). [DOI] | |
| 2017 | Nugent, M; Wang, J; Lawrence, G; Zurawski, T; Geoghegan, JA; Dolly, JO (2017) 'Conjugate of an IgG Binding Domain with Botulinum Neurotoxin A Lacking the Acceptor Moiety Targets Its SNARE Protease into TrkA-Expressing Cells When Coupled to Anti-TrkA IgG or Fc-βNGF'. Bioconjugate Chemistry, 28 (6). [DOI] | |
| 2015 | Ovespian, S.V.; Bodeker, M.D.; O’Leary, V.B.; Lawrence, G.W.; Oliver Dolly, J. (2015) 'Internalization and retrograde axonal trafficking of tetanus toxin in motor neurons and trans-synaptic propagation at central synapses exceed those of its C-terminal-binding fragments'. Brain structure & function, 220 . [Link] [DOI] | |
| 2014 | Dolly, JO; Lawrence, GW (2014) 'Chapter 3: Molecular basis for the therapeutic effectiveness of botulinum neurotoxin type A'. Neurourology and Urodynamics, 33 Suppl 3 . [DOI] | |
| 2014 | Dolly, J. O.; O'Leary, V. B.; Lawrence, G. W.; Ovsepian, S. V. (2014) 'Pharmacology of Botulinum Neurotoxins: Exploitation of Their Multifunctional Activities as Transmitter Release Inhibitors and Neuron-Targeted Delivery Vehicles'. Molecular Aspects Of Botulinum Neurotoxin, Vol 4, 4 . [DOI] | |
| 2014 | Lawrence, GW; Wang, J; Brin, MF; Aoki, KR; Wheeler, L; Dolly, JO (2014) 'Fusion of Golgi-derived vesicles mediated by SNAP-25 is essential for sympathetic neuron outgrowth but relatively insensitive to botulinum neurotoxins in vitro'. The FEBS journal, 281 (14). [DOI] | |
| 2013 | Schulte-Baukloh, H.; Priefert, J.; Knispel, H.H.; Lawrence, G.W.; Miller, K.; Neuhaus, J. (2013) 'Botulinum toxin a detrusor injections reduce postsynaptic muscular M2, M3, P2X2, and P2X3 receptors in children and adolescents who have neurogenic detrusor overactivity: A single-blind study'. Urology, 81 . [Link] [DOI] | |
| 2013 | Lawrence, G.W.; Ovsepian, S.V.; Wang, J.; Aoki, K.R.; Dolly, J.O. (2013) 'Therapeutic effectiveness of botulinum neurotoxin A: Potent blockade of autonomic transmission by targeted cleavage of only the pertinent SNAP-25'. Neuropharmacology, 70 . [Link] [DOI] | |
| 2013 | Meng, J; Wang, J; Lawrence, GW; Dolly, JO (2013) 'Molecular components required for resting and stimulated endocytosis of botulinum neurotoxins by glutamatergic and peptidergic neurons'. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 27 (8). [DOI] | |
| 2012 | Edupuganti, OP; Ovsepian, SV; Wang, J; Zurawski, TH; Schmidt, JJ; Smith, L; Lawrence, GW; Dolly, JO (2012) 'Targeted delivery into motor nerve terminals of inhibitors for SNARE-cleaving proteases via liposomes coupled to an atoxic botulinum neurotoxin'. The FEBS journal, 279 (14). [DOI] | |
| 2012 | Lawrence, G.W.; Ovsepian, S.V.; Wang, J.; Aoki, K.R.; Dolly, J.O. (2012) 'Extravesicular intraneuronal migration of internalized botulinum neurotoxins without detectable inhibition of distal neurotransmission'. Biochemical Journal, 441 . [Link] [DOI] | |
| 2012 | Wang, J; Zurawski, TH; Meng, J; Lawrence, GW; Aoki, KR; Wheeler, L; Dolly, JO (2012) 'Novel chimeras of botulinum and tetanus neurotoxins yield insights into their distinct sites of neuroparalysis'. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 26 (12). [DOI] | |
| 2011 | O'Leary, VB; Ovsepian, SV; Raghunath, A; Huo, Q; Lawrence, GW; Smith, L; Dolly, JO (2011) 'Innocuous full-length botulinum neurotoxin targets and promotes the expression of lentiviral vectors in central and autonomic neurons'. Gene Therapy, 18 (7). [DOI] | |
| 2010 | Lawrence, G.W.; Aoki, K.R.; Dolly, J.O. (2010) 'Excitatory cholinergic and purinergic signaling in bladder are equally susceptible to botulinum neurotoxin a consistent with co-release of transmitters from efferent fibers'. Journal of Pharmacology and Experimental Therapeutics, 334 . [Link] [DOI] | |
| 2010 | Wang, J; Zurawski, TH; Meng, J; Lawrence, G; Olango, WM; Finn, DP; Wheeler, L; Dolly, JO (2010) 'A dileucine in the protease of botulinum toxin A underlies its long-lived neuroparalysis: transfer of longevity to a novel potential therapeutic'. The Journal of biological chemistry, 286 (8). [DOI] | |
| 2009 | Meng, J.; Ovsepian, S.V.; Wang, J.; Pickering, M.; Sasse, A.; Aoki, K.R.; Lawrence, G.W.; Dolly, J.O. (2009) 'Activation of TRPV1 mediates calcitonin gene-related peptide release, which excites trigeminal sensory neurons and is attenuated by a retargeted botulinum toxin with anti-nociceptive potential'. Journal of Neuroscience, 29 . [Link] [DOI] | |
| 2009 | Dolly, JO; Lawrence, GW; Meng, J; Wang, J; Ovsepian, SV (2009) 'Neuro-exocytosis: botulinum toxins as inhibitory probes and versatile therapeutics'. Current Opinion in Pharmacology, 9 (3). [DOI] | |
| 2008 | Wang, J; Meng, J; Lawrence, GW; Zurawski, TH; Sasse, A; Bodeker, MO; Gilmore, MA; Fernández-Salas, E; Francis, J; Steward, LE; Aoki, KR; Dolly, JO (2008) 'Novel chimeras of botulinum neurotoxins A and E unveil contributions from the binding, translocation, and protease domains to their functional characteristics'. The Journal of biological chemistry, 283 (25). [DOI] | |
| 2007 | Dolly, J. Oliver; Lawrence, Gary (2007) 'Mechanistic basis for the therapeutic effectiveness of botulinum toxin A on over-active cholinergic nerves'. Clinical Uses Of Botulinum Toxins, . | |
| 2007 | Meng, J.; Wang, J.; Lawrence, G.; Dolly, J.O. (2007) 'Synaptobrevin I mediates exocytosis of CGRP from sensory neurons and inhibition by botulinum toxins reflects their anti-nociceptive potential'. Journal of Cell Science, 120 . [Link] [DOI] | |
| 2006 | Lawrence, G; Wang, J; Chion, CK; Aoki, KR; Dolly, JO (2006) 'Two protein trafficking processes at motor nerve endings unveiled by botulinum neurotoxin E'. The Journal of pharmacology and experimental therapeutics, 320 (1). [DOI] | |
| 2003 | Foran, P.G.; Mohammed, N.; Lisk, G.O.; Nagwaney, S.; Lawrence, G.W.; Johnson, E.; Smith, L.; Roger Aoki, K.; Dolly, J.O.; (2003) 'Evaluation of the therapeutic usefulness of botulinum neurotoxin B, C1, E, and F compared with the long lasting type A: Basis for distinct durations of inhibition of exocytosis in central neurons'. Journal of Biological Chemistry, . [DOI] | |
| 2002 | Lawrence, G.W.; Foran, P.; Dolly, J.O.; (2002) 'Insights into a basis for incomplete inhibition by botulinum toxin A of Ca2+-evoked exocytosis from permeabilised chromaffin cells'. Toxicology, . [DOI] | |
| 2002 | Gary W. Lawrence; J. Oliver Dolly (2002) 'Multiple forms of SNARE complexes in exocytosis from chromaffin cells: effects of Ca2+, MgATP and botulinum toxin type A'. J Cell Sci, . [Link] [DOI] | |
| 2002 | Gary W. Lawrence; J. Oliver Dolly (2002) 'Ca2+-induced changes in SNAREs and synaptotagmin I correlate with triggered exocytosis from chromaffin cells: insights gleaned into the signal transduction using trypsin and botulinum toxins'. J Cell Sci, . [Link] [DOI] | |
| 2001 | Li, Y.; Foran, P.; Lawrence, G.; Mohammed, N.; Chan-Kwo-Chion, C.-K.-N.; Lisk, G.; Aoki, R.; Dolly, O.; (2001) 'Recombinant Forms of Tetanus Toxin Engineered for Examining and Exploiting Neuronal Trafficking Pathways'. Journal of Biological Chemistry, . [DOI] | |
| 2000 | F.A. Meunier; C. Mattei; P. Chameau; G. Lawrence; C. Colasante; A.S. Kreger; J.O. Dolly; J. Molgo (2000) 'Trachynilysin mediates SNARE-dependent release of catecholamines from chromaffin cells via external and stored Ca2+'. J Cell Sci, . [Link] [DOI] | |
| 1999 | O'Sullivan, G.A.; Mohammed, N.; Foran, P.G.; Lawrence, G.W.; Dolly, J.O.; (1999) 'Rescue of exocytosis in botulinum toxin A-poisoned chromaffin cells by expression of cleavage-resistant SNAP-25. Identification of the minimal essential C-terminal residues'. Journal of Biological Chemistry, . [DOI] | |
| 1997 | Lawrence, G.W.; Foran, P.; Mohammed, N.; DasGupta, B.R.; Dolly, J.O.; (1997) 'Importance of two adjacent C-terminal sequences of SNAP-25 in exocytosis from intact and permeabilized chromaffin cells revealed by inhibition with botulinum neurotoxins A and E'. Journal of Biochemistry, . [DOI] | |
| 1996 | Lawrence, G.W.; Foran, P.; Dolly, J.O.; (1996) 'Distinct exocytotic responses of intact and permeabilised chromaffin cells after cleavage of the 25-kDa synaptosomal-associated protein (SNAP-25) or synaptobrevin by botulinum toxin A or B'. European Journal of Biochemistry, . [DOI] | |
| 1996 | Foran, P.; Lawrence, G.W.; Shone, C.C.; Foster, K.A.; Dolly, J.O.; (1996) 'Botulinum neurotoxin C1 cleaves both syntaxin and SNAP-25 in intact and permeabilized chromaffin cells: Correlation with its blockade of catecholamine release'. Journal of Biochemistry, . [DOI] | |
| 1995 | Foran, P.; Lawrence, G.; Dolly, J.O.; (1995) 'Blockade by Botulinum Neurotoxin B of Catecholamine Release from Adrenochromaffin Cells Correlates with Its Cleavage of Synaptobrevin and a Homolog Present on the Granules'. Journal of Biochemistry, . [DOI] | |
| 1994 | Dolly, J.O.; De Paiva, A.; Foran, P.; Lawrence, G.; Daniels-Holgate, P.; Ashton, A.C.; (1994) 'Probing the process of transmitter release with botulinum and tetanus neurotoxins'. Seminars in the Neurosciences, . [DOI] | |
| 1994 | LAWRENCE, G.W.; WELLER, U.; DOLLY, J.O.; (1994) 'Botulinum A and the light chain of tetanus toxins inhibit distinct stages of Mg · ATPâdependent catecholamine exocytosis from permeabilised chromaffin cells'. European Journal of Biochemistry, . [DOI] | |
| 1993 | de Paiva A; Poulain B; Lawrence GW; Shone CC; Tauc L; Dolly JO (1993) 'A role for the interchain disulfide or its participating thiols in the internalization of botulinum neurotoxin A revealed by a toxin derivative that binds to ecto-acceptors and inhibits transmitter release intracellularly'. The Journal of biological chemistry, . [Link] [DOI] |
Other Publication
| Year | Publication | |
|---|---|---|
| 2023 | Corasaniti, M.T.; Bagetta, G.; Nicotera, P.; Tarsitano, A.; Tonin, P.; Sandrini, G.; Lawrence, G.W.; Scuteri, D. (2023) Safety of Onabotulinumtoxin A in Chronic Migraine: A Systematic Review and Meta-Analysis of Randomized Clinical Trials. [Link] [DOI] | |
| 2018 | Zurawski, Tomas H.; Lawrence, Gary W.; Broide, Ron S.; Brideau-Andersen, Amy; Brin, Mitchell F.; Dolly, J. Oliver (2018) LONG-DISTANCE SPREAD OF BOTULINUM NEUROTOXIN TYPE A IN MICE PERSISTS AFTER PERIPHERAL NERVE AXOTOMY. | |
| 2001 | Dolly, JO; O'Sullivan, G; Mohammed, N; Foran, P; Lawrence, GW; Meunier, E; Lisk, G (2001) Molecular basis of the therapeutic applications of botulinum toxins. |
Research Interests
Deciphering molecular events in the ubiquitous process for the release of chemical transmitters from different nerve types, by Ca2+-regulated exocytosis.
Neurotransmitter release /neurotransmission from different peripheral neuron types (sensory, motor, sympathetic or parasympathetic) is studied using primary neuron cultures, in tissues and in vivo. Botulinum toxins are used to potently and selectively inactivate key proteins called SNAREs that catalyse membrane fusion, a critical step in the release from nerves of chemical transmitters stored inside intracellular membrane vesicles. Key goals are to distinguish the distinct contributions of individual SNAREs to exocytosis from different neuron types, decipher their differential regulation by intracellular calcium ion concentrations, and to delineate neuron types most susceptible to the botulinum toxins.
Contribution of SNARE-mediated membrane trafficking to the sensitisation of nociceptor sub-types implicated in chronic pain
Chronic pain affects an estimated 20 percent of people in Europe, severely impairing quality of life for sufferers and placing a huge burden on public healthcare. Increased sensitivity of sensory neurons to external stimuli contributes to abnormal pain generation. Such sensitisation is being investigated in primary neuron tissue, cell cultures and in vivo using a combination of fluorescence microscopy, biochemical assay, and animal behaviour models. Aims include the discovery of factors produced in injured/diseased tissues that sensitise sensory neurons, identification of their molecular and cellular targets, and definition of the signalling processes involved, particularly the influence on neuron sensitivity of nocifensive channels trafficking. I am also interested in uncovering the molecular and cellular mechanisms involved in detecting and encoding the severity of environmental hazards.
Development of novel neurotherapeutics for persistent conditions lacking effective, long-acting and non-addictive medicines.
Using the information gleaned from the above-noted studies, by protein engineering the therapeutically-beneficial characteristics of botulinum neurotoxin A have been combined with those of variant subtypes in proprietary chimeras and hybrids that exhibit improved versatility and efficacy for new medical applications. These are best exemplified by a newly-developed, potent and long-acting form that effectively relieves chronic pain in pre-clinical studies; international patents for these innovative biotherapeutics have been granted recently. Development of these high-potency biotherapeutics is undertaken in a purpose-built cleanroom / containment facility.