Dr Stuart Nicklin

  • Reader (Institute of Cardiovascular and Medical Sciences)

telephone: 01413302521
email: Stuart.Nicklin@glasgow.ac.uk


My primary research interests are in cardiovascular gene therapy. One of the main limitations for clinical gene therapy is appropriate gene delivery to the target site. It would be particularly beneficial to target vascular endothelium safely and efficiently after systemic administration. A particular focus of my work has been on the development of endothelial-targeted adenoviral and adeno-associated viral vectors. This has been achieved through developing approaches for the isolation of vascular endothelium-selective targeting peptides through phage display. My interests also extend into analysis and identification of efficient promoters for driving gene expression for provision of an additional level of selectivity as well as development of vectors expressing new candidate genes for testing in appropriate models. Generation of these vectors will allow us to extend into pre-clinical studies with candidate therapeutic transgenes for assessing vector efficacy and safe

Research:

Jump to: 2013 | 2012 | 2011 | 2010 | 2009 | 2008 | 2007 | 2006 | 2005 | 2004 | 2003 | 2002 | 2001
Number of items: 60.

2013

Jenkins, L., Harries, N., Lappin, J.E., MacKenzie, A.E., Neetoo-Isseljee, Z., Southern, C., McIver, E.G., Nicklin, S.A., Taylor, D.L., and Milligan, G. (2013) Antagonists of GPR35 display high species ortholog selectivity and varying modes of action. Journal of Pharmacology and Experimental Therapeutics, 343 (3). pp. 683-695. ISSN 0022-3565 (doi:10.1124/jpet.112.198945)

2012

Robertson, K.E., McDonald, R.A., Oldroyd, K.G., Nicklin, S.A., and Baker, A.H. (2012) Prevention of coronary in-stent restenosis and vein graft failure: Does vascular gene therapy have a role? Pharmacology and Therapeutics, 136 (1). pp. 23-34. ISSN 0163-7258 (doi:10.1016/j.pharmthera.2012.07.002)

Coughlan, L. et al. (2012) Ad5:Ad48 hexon hypervariable region substitutions lead to toxicity and increased inflammatory responses following intravenous delivery. Molecular Therapy, 20 (12). pp. 2268-2281. ISSN 1525-0016 (doi:10.1038/mt.2012.162)

Flores, M., Work, L.M., Douglas, K., Denby, L., Dominiczak, A.F., Graham, D., and Nicklin, S.A. (2012) Angiotensin-(1-9) attenuates cardiac fibrosis in the stroke-prone spontaneously hypertensive rat via the angiotensin type 2 receptor. Hypertension, 59 (2). pp. 300-307. ISSN 0194-911X (doi:10.1161/HYPERTENSIONAHA.111.177485)

Flores-Munoz, M., Work, L.M., Douglas, K., Denby, L., Dominiczak, A.F., Graham, D., and Nicklin, S.A. (2012) Angiotensin (1-9) attenuates cardiac fibrosis in the stroke-prone spontaneously hypertensive rat via the angiotensin type 2 receptor. Hypertension, 59 (2). pp. 300-3007. ISSN 0194-911X

Flores-Muñoz, M., Godinho, B.M.D.C., Almalik, A., and Nicklin, S.A. (2012) Adenoviral delivery of angiotensin-(1-7) or angiotensin-(1-9) inhibits cardiomyocyte hypertrophy via the mas or angiotensin Type 2 receptor. PLoS ONE, 7 (9). e45564. ISSN 1932-6203 (doi:10.1371/journal.pone.0045564)

2011

Flores-Munoz, M., Smith, N. J., Haggerty, C., Milligan, G,, and Nicklin, S. A. (2011) Angiotensin1-9 antagonises pro-hypertrophic signalling in cardiomyocytes via the angiotensin type 2 receptor. Journal of Physiology, 589 (4). pp. 939-951. ISSN 0022-3751 (doi:10.1113/jphysiol.2010.203075)

2010

Alba, R. et al. (2010) Biodistribution and retargeting of FX-binding ablated adenovirus serotype 5 vectors. Blood, 14 (116). pp. 2656-2664. ISSN 0006-4971 (doi:10.1182/blood-2009-12-260026)

Bradshaw, A.C., Parker, A.L., Duffy, M.R., Coughlan, L., van Rooijen, N., Kahari, V.M., Nicklin, S.A., and Baker, A.H. (2010) Requirements for receptor engagement during infection by adenovirus complexed with blood coagulation factor X. PLoS Pathogens, 6 (10). e1001142. ISSN 1553-7366 (doi:10.1371/journal.ppat.1001142)

Coughlan, L., Alba, R., Parker, A.L., Bradshaw, A.C., Mcneish, I.A., Nicklin, S., and Baker, A. (2010) Tropism-modification strategies for targeted gene delivery using adenoviral vectors. Viruses, 2 (10). pp. 2290-2355. ISSN 1999-4915 (doi:10.3390/v2102290)

Padmanabhan, S. et al. (2010) Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension. PLoS Genetics, 6 (10). e1001177. ISSN 1553-7390 (doi:10.1371/journal.pgen.1001177)

2009

Alba, R. et al. (2009) Identification of coagulation factor (F)X binding sites on the adenovirus serotype 5 hexon: effect of mutagenesis on FX interactions and gene transfer. Blood, 114 (5). pp. 965-971. ISSN 0006-4971 (doi:10.1182/blood-2009-03-208835)

Nicol, C.G., Denby, L., Lopez-Franco, O., Masson, R., Halliday, C.A., Nicklin, S.A., Kritz, A., Work, L.M., and Baker, A.H. (2009) Use of in vivo phage display to engineer novel adenoviruses for targeted delivery to the cardiac vasculature. Febs Letters, 583 (12). pp. 2100-2107. ISSN 0014-5793 (doi:10.1016/j.febslet.2009.05.037)

Parker, A.L., Waddington, S.N., Buckley, S.M.K., Custers, J., Havenga, M.J.E., van Rooijen, N., Goudsmit, J., Mcvey, J.H., Nicklin, S.A., and Baker, A.H. (2009) Effect of neutralizing sera on factor X-mediated adenovirus serotype 5 gene transfer. Journal of Virology, 83 (1). pp. 479-483. ISSN 0022-538X (doi:10.1128/JVI.01878-08)

Greig, J. et al. (2009) Influence of Coagulation Factor X on In Vitro and In Vivo Gene Delivery by Adenovirus (Ad) 5, Ad35, and Chimeric Ad5/Ad35 Vectors. Molecular Therapy, 17 (10). pp. 1683-1691. ISSN 0006-4971 (doi:10.1038/mt.2009.152)

Kettlewell, S., Cabrero, P., Nicklin, S.A., Dow, J.A.T., Davies, S.A., and Smith, G.L. (2009) Changes of intra-mitochondrial Ca2+ in adult ventricular cardiomyocytes examined using a novel fluorescent Ca2+ indicator targeted to mitochondria. Journal of Molecular and Cellular Cardiology, 46 (6). pp. 891-901. ISSN 0022-2828 (doi:10.1016/j.yjmcc.2009.02.016)

Lenaerts, L, Mcvey, JH, Baker, AH, Denby, L, Nicklin, SA, Verbeken, E, and Naesens, L (2009) Mouse adenovirus type 1 and human adenovirus type 5 differ in endothelial cell tropism and liver targeting. Journal of Gene Medicine, 11 (2). pp. 119-127. (doi:10.1002/jgm.1283)

Masson, R. et al. (2009) Onset of experimental severe cardiac fibrosis is mediated by overexpression of angiotensin-converting enzyme 2. Hypertension, 53 (4). pp. 694-700. ISSN 0194-911X (doi:10.1161/HYPERTENSIONAHA.108.122333)

2008

Parker, A.L., Nicklin, S.A., and Baker, A.H. (2008) Interactions of adenovirus vectors with blood: implications for intravascular gene therapy applications. Current Opinion in Molecular Therapeutics, 10 (5). pp. 439-448. ISSN 1464-8431

White, K. et al. (2008) Engineering adeno-associated virus 2 vectors for targeted gene delivery to atherosclerotic lesions. Gene Therapy, 15 (6). pp. 443-451. ISSN 0969-7128 (doi:10.1038/sj.gt.3303077)

Waddington, S. et al. (2008) Adenovirus serotype 5 hexon mediates liver gene transfer. Cell, 132 (3). pp. 397-409. ISSN 0092-8674 (doi:10.1016/j.cell.2008.01.016 )

Flores-Munoz, M, Baker, AH, and Nicklin, SA (2008) Development of a gene transfer vector expressing angiotensin 1-7 and assessment of its effects on cardiac hypertrophy. Journal of Human Hypertension, 22 (10). p. 723. ISSN 0950-9240

Greig, JA, Mcvey, JH, Waddington, SN, Parker, A, Buckley, SMK, Havenga, MJE, Nicklin, SA, and Baker, AH (2008) Factor X enhances binding and transduction of human cancer cell lines by adenovirus (Ad) serotype 5 vectors but not by Ad35. Human Gene Therapy, 19 (4). p. 398. ISSN 1043-0342

Nicklin, SA, and Baker, AH (2008) Efficient Vascular Endothelial Gene Transfer Following Intravenous Adenovirus Delivery. Molecular Therapy, 16 (12). pp. 1904-1905.

Parker, A, Parker, A, Mcvey, JH, Waddington, SN, Buckley, SMK, Francischetti, IMB, Monteiro, RQ, Nicklin, SA, and Baker, AH (2008) An exosite within the human FX serine protease domain mediates cell transduction of AD5: FX complexes. Human Gene Therapy, 19 (4). p. 34.

2007

Waddington, S.N., Parker, A.L., Havenga, M., Nicklin, S.A., Buckley, S.M., McVey, J.H., and Baker, A.H. (2007) Targeting of adenovirus serotype 5 (Ad5) and 5/47 pseudotyped vectors in vivo: Fundamental involvement of coagulation factors and redundancy of CAR binding by Ad5. Journal of Virology, 81 (17). pp. 9568-9571. ISSN 0022-538X (doi:10.1128/JVI.00663-07)

Baker, AH, Nicklin, SA, and White, K (2007) Novel vectors for in vivo gene delivery to vascular tissue. Expert Opinion on Biological Therapy, 7 . pp. 809-821. (doi:10.1517/14712598.7.6.809)

Denby, L., Work, L.M., Von Seggern, D.J., Wu, E., Mcvey, J.H., Nicklin, S.A., and Baker, A.H. (2007) Development of renal-targeted vectors through combined in vivo phage display and capsid engineering of adenoviral fibers from serotype 19p. Molecular Therapy, 15 (9). pp. 1647-1654. ISSN 0006-4971 (doi:10.1038/sj.mt.6300214)

Kritz, AB, Nicol, CG, Dishart, KL, Nelson, R, Holbeck, S, Von Seggern, DJ, Work, LM, Mcvey, JH, Nicklin, SA, and Baker, AH (2007) Adenovirus 5 fibers mutated at the putative HSPG-binding site show restricted retargeting with targeting peptides in the HI loop. Molecular Therapy, 15 . pp. 741-749. (doi:10.1038/sj.mt.6300094)

Parker, AL, Mcvey, JH, Doctor, JH, Lopez-Franco, O, Waddington, SN, Havenga, MJE, Nicklin, SA, and Baker, AH (2007) Influence of coagulation factor zymogens on the infectivity of adenoviruses pseudotyped with fibers from subgroup D. Journal of Virology, 81 . pp. 3627-3631. ISSN 0022-538X (doi:10.1128/JVI.02786-06)

2006

Parker, A.L. et al. (2006) Multiple vitamin K-dependent coagulation zymogens promote adenovirus-mediated gene delivery to hepatocytes in vitro and in vivo. Blood, 108 (8). pp. 2554-2561. ISSN 0006-4971 (doi:10.1182/blood-2006-04-008532 )

Parker, AL et al. (2006) Multiple vitamin K-dependent coagulation zymogens promote adenovirus-mediated gene delivery to hepatocytes. Blood, 108 . pp. 2554-2561. (doi:10.1182/blood-2006-04-008532)

Work, L.M. et al. (2006) Vascular bed-targeted in vivo gene delivery using tropism-modified adeno-associated viruses. Molecular Therapy, 13 (4). pp. 683-693. (doi:10.1016/j.ymthe.2005.11.013)

2005

Baker, AH, Kritz, A, Work, LM, Nicklin, SA, and Nicklin, A (2005) Cell-selective viral gene delivery vectors for the vasculature. Experimental Physiology, 90 . pp. 27-31. (doi:10.1113/expphysiol.2004.028126)

Baker, AH, Nemerow, GR, Nicklin, SA, and Wu, E (2005) The influence of adenovirus fiber structure and function on vector development for gene therapy. Molecular Therapy, 12 . pp. 384-393. (doi:10.1016/j.ymthe.2005.05.008)

Denby, L., Nicklin, S.A., and Baker, A.H. (2005) Adeno-associated virus (AAV)-7 and-8 poorly transduce vascular endothelial cells and are sensitive to proteasomal degradation. Gene Therapy, 12 . pp. 1534-1538. ISSN 0969-7128 (doi:10.1038/sj.gt.3302564)

Miller, W.H., Nicklin, S.A., Baker, A.H., and Dominiczak, A. (2005) Gene transfer and the cardiovascular system. In: Raizada, M.K., Paton, J.F.R., Kasparov, S. and Katovich, M.J. (eds.) Cardiovascular Genomics. Series: Contemporary cardiology . Humana Press, Totowa, NJ, USA, pp. 175-196. ISBN 9781588294005

Parker, AL, Fisher, KD, Oupicky, D, Read, ML, Nicklin, SA, Baker, AH, and Seymour, LW (2005) Enhanced gene transfer activity of peptide-targeted gene-delivery vectors. Journal of Drug Targeting, 13 . pp. 39-51. (doi:10.1080/10611860400020449)

Work, LM, Nicol, CG, Denby, L, and Nicklin, SA (2005) In vivo biopanning: a methodological approach to identifuing novel targeting ligands. Methods in Molecular Medicine, 108 . pp. 395-413.

2004

Denby, L., Work, L.M., Graham, D., Hsu, C., Von Seggern, D.J., Nicklin, S.A., and Baker, A.H. (2004) Adenoviral serotype 5 vectors pseudotyped with fibers from subgroup D show modified tropism in vitro and in vivo. Human Gene Therapy, 15 (11). pp. 1054-1064. ISSN 1043-0342

Nicklin, SA, White, SJ, Nicol, CG, Von Seggern, DJ, and Baker, AH (2004) In vitro and in vivo characterisation of endothelial cell selective adenoviral vectors. Journal of Gene Medicine, 6 . pp. 300-308. (doi:10.1002/jgm.526)

Nicol, CG, Graham, D, Miller, WH, White, SJ, Smith, TAG, Nicklin, SA, Stevenson, SC, and Baker, AH (2004) Effect of adenovirus serotype 5 fiber and penton modifications on in vivo tropism in rats. Molecular Therapy, 10 . pp. 344-354. (doi:10.1016/j.ymthe.2004.05.020)

Papadakis, ED, Nicklin, SA, Baker, AH, and White, SJ (2004) Promoters and control elements: Designing expression cassettes for gene therapy. Current Gene Therapy, 4 . pp. 89-113.

Wan, S, George, SJ, Nicklin, SA, Yim, APC, and Baker, AH (2004) Overexpression of p53 increases lumen size and blocks neointima formation in porcine interposition vein grafts. Molecular Therapy, 9 . pp. 689-698. (doi:10.1016/j.ymthe.2004.02.005)

White, SJ, Nicklin, SA, Buning, H, Brosnan, MJ, Leike, K, Papadakis, ED, Hallek, M, and Baker, AH (2004) Targeted gene delivery to vascular tissue in vivo by tropism-modified adeno-associated virus vectors. Circulation, 109 . pp. 513-519. (doi:10.1161/01.CIR.0000109697.68832.5D)

Work, LM, Nicklin, SA, Brain, NJR, Dishart, KL, Von Seggern, DJ, Hallek, M, Buning, H, and Baker, AH (2004) Development of efficient viral vectors selective for vascular smooth muscle cells. Molecular Therapy, 9 . pp. 198-208. (doi:10.1016/j.ymthe.2003.11.006)

Work, LM, Ritchie, N, Nicklin, SA, Reynolds, PN, and Baker, AH (2004) Dual targeting of gene delivery by genetic modification of adenovirus serotype 5 fibers and cell-selective transcriptional control. Gene Therapy, 11 . pp. 1296-1300. (doi:10.1038/sj.gt.3302292)

2003

Buning, H, Nicklin, SA, Perabo, L, Hallek, M, and Baker, AH (2003) AAV-based gene transfer. Current Opinion in Molecular Therapeutics, 5 . pp. 367-375.

Dishart, K.L. et al. (2003) Third-generation lentivirus vectors efficiently transduce and phenotypically modify vascular cells: implications for gene therapy. Journal of Molecular and Cellular Cardiology, 35 (7). pp. 739-748. ISSN 0022-2828 (doi:10.1016/S0022-2828(03)00136-6)

Nicklin, S.A., and Baker, A.H. (2003) Development of targeted viral vectors for cardiovascular gene therapy. In: Setlow, J.K. (ed.) Genetic Engineering, Principles and Methods. Kluwer Academic, Dordrecht, The Netherlands, pp. 15-49. ISBN 9780306477768

Nicklin, SA, Dishart, KL, Buening, H, Reynolds, PN, Hallek, M, Nemerow, GR, Von Seggern, DJ, and Baker, AH (2003) Transductional and transcriptional targeting of cancer cells using genetically engineered viral vectors. Cancer Letters, 201 . pp. 165-173. (doi:10.1016/j.canlet.2003.07.003)

Work, LM, Nicklin, SA, and Baker, AH (2003) Targeting Gene Therapy Vectors to the Vascular Endothelium. Current Atherosclerosis Reports, 5 (3). pp. 163-170.

2002

Baker, AH, Nicklin, SA, White, SJ, and Work, LM (2002) Use of phage display to identify novel peptides for targeted gene therapy. Gene Therapy Methods, 346 . pp. 157-176.

Fennell, JP, Brosnan, MJ, Frater, AJ, Hamilton, CA, Alexander, MY, Nicklin, SA, Heistad, DD, Baker, AH, and Dominiczak, AF (2002) Adenovirus-mediated overexpression of extracellular superoxide dismutase improves endothelial dysfunction in a rat model of hypertension. Gene Therapy, 9 . pp. 110-117. (doi:10.1038/sj/gt/3301633)

Nicklin, SA, and Baker, AH (2002) Tropism-Modified Adenoviral and Adeno-Associated Viral Vectors for Gene Therapy. Current Gene Therapy, 2 (3). pp. 273-293.

2001

Nicklin, SA, Buening, H, Dishart, KL, De Alwis, M, Girod, A, Hacker, U, Thrasher, AJ, Ali, RR, Hallek, M, and Baker, AH (2001) Efficient and selective AAV2-mediated gene transfer directed to human vascular endothelial cells. Molecular Therapy, 4 . pp. 174-181.

Nicklin, SA, Reynolds, PN, Brosnan, MJ, White, SJ, Curiel, DT, Dominiczak, AF, and Baker, AH (2001) Analysis of cell-specific promoters for viral gene therapy targeted at the vascular endothelium. Hypertension, 38 . pp. 65-70.

Nicklin, SA, Von Seggern, DJ, Work, LM, Pek, DC, Dominiczak, AF, Nemerow, GR, and Baker, AH (2001) Ablating adenovirus type 5 fiber-CAR binding and HI loop insertion of the SIGYPLP peptide generate an endothelial cell-selective adenovirus. Molecular Therapy, 4 . pp. 534-542. (doi:10.1006/mthe.2001.0489)

Reynolds, PN, Nicklin, SA, Kaliberova, L, Boatman, BG, Grizzle, WE, Balyasnikova, IV, Baker, AH, Danilov, SM, and Curiel, DT (2001) Combined transductional and transcriptional targeting improves the specificity of transgene expression in vivo. Nature Biotechnology, 19 . pp. 838-842.

White, SJ, Nicklin, SA, Sawamura, T, and Baker, AH (2001) Identification of peptides that target the endothelial cell-specific LOX-1 receptor. Hypertension, 37 . pp. 449-455.

This list was generated on Fri May 3 01:57:29 2013 BST.

Grants and Awards listed are those received whilst working with the University of Glasgow.

  • Ad-Vec: Adenovirus Vector Technology: Next Generation Systems for Medical Therapy
    European Commission
    2013 - 2017
     
  • ADENOVIRUS SEROTYPE 49: A NOVEL VECTOR FOR VASCULAR GENE THERAPY
    British Heart Foundation
    2012 - 2015
     
  • The mitochondrial-targeted antioxidant, MitoQ10: a novel therapeutic agent for cardiovascular disease.
    British Heart Foundation
    2012 - 2012
     
  • Gene Therapy for Vein Graft Failure
    MRC
    2011 - 2016
     
  • Angiotensin 1-9 and angiotensin 1-7: assessment of their mechanisms of action as counter-regulatory renin angiotensin system peptides in cardiovascular disease
    British Heart Foundation
    2011 - 2014
     
  • Refinement and assessment of a novel adenovirus targeting platform for application to human gene therapy
    BBSRC
    2011 - 2014
     
  • Improved gene therapy via genetic modification of the adenovirus capsid to ablate interaction with blood coagulation factor X
    BBSRC
    2011 - 2012
     
  • Dissecting the mechanism of action of the novel renin angiotensin hormone angiotensin1-9
    MRC
    2010 - 2013
     
  • Interrogation and manipulation of miRNA in acute vascular injury
    British Heart Foundation
    2010 - 2014
     
  • Interrogation of the adenovirus hexon: A new paradigm for virus biology and application to therapeutic gene delivery
    BBSRC
    2009 - 2012
     
  • Evaluating the impact of coagulation factors on gene delivery using pseudotyped adenoviruses - receptor usage, bioavailability and toxicology
    BBSRC
    2009 - 2011
     
  • Development of efficient disease-regulated expression cassettes for gene therapy using microRNA targeting sequences
    BBSRC
    2008 - 2011
     
  • The role of vitamin K-dependent coagulation zymogens in adenovirus dissemination and pharmacodynamics in vivo.
    Wellcome Trust
    2008 - 2009
     
  • Does ACE2 have a protective role in the heart? Systematic analysis of ACE2 in a disease model
    British Heart Foundation
    2007 - 2010
     
  • Evaluating the impact of coagulation factors on gene delivery using pseudotyped adenoviruses - receptor usage, bioavailability and toxicology
    BBSRC
    2007 - 2011
     
  • 10th annual meeting of the American Society of Gene Therapy
    Royal Society
    2007 - 2007
     
  • The 8th international adenovirus meeting
    Royal Society
    2006 - 2006
     
  • Novel molecular tools to modulate the renin angiotensin system in vivo
    Royal Society
    2005 - 2006
     
  • Annual meeting of the American society of gene therapy
    Royal Society
    2005 - 2005
     
  • In vivo targeting of atherosclerotic plaques - a potential for therapeutics and diagnosis
    British Heart Foundation
    2005 - 2009
     
  • Development of a novel adenovirus-based, targetable vector for selective in vivo gene delivery
    British Heart Foundation
    2003 - 2005
     
  • Development of viral vectors for regulated expression of putative therapeutic genes in a model of human hypertension
    British Heart Foundation
    2003 - 2006