Institute of Cardiovascular and Medical Sciences

Dr Lorraine Work

  • Lecturer (Institute of Cardiovascular and Medical Sciences)

telephone: 01413305869/4962
email: Lorraine.Work@glasgow.ac.uk


As a recently appointed lecturer on the BBSRC Integrative Mammalian Biology (IMB) initiative the central theme of my research is to allow the translation of knowledge gained from single molecules back to the whole organism, including in vivo studies.  To date, my research has focused on therapeutic intervention for cardiovascular disease using both pharmacological agents and gene delivery protocols.  A central feature in both these disciplines is the relative lack of targeting capacity for either agent towards a specific disease site.  Therefore, integral to my research interests is the identification of novel targeting ligands identified using phage display which may subsequently be used to direct both gene- and pharmacology-based interventions.  In the case of gene-based therapy, I have focused on viral vectors to deliver reporter genes to localise gene expression following genetic alteration of the virus capsid to allow de- and re-targeting.  Additionally, the combination of pharmacological and gene-based therapies may provide further benefit than the use of each approach alone for a number of diseases affecting the cardiovascular system and stroke.

List all by: Type | Date

Jump to: 2013 | 2012 | 2010 | 2009 | 2008 | 2007 | 2006 | 2005 | 2004 | 2003 | 2002 | 2001
Number of items: 25.

2013

Ord, E.N.J., Shirley, R., McClure, J.D., McCabe, C., Kremer, E.J., Macrae, I.M., and Work, L.M. (2013) Combined antiapoptotic and antioxidant approach to acute neuroprotection for stroke in hypertensive rats. Journal of Cerebral Blood Flow and Metabolism, 33 (8). pp. 1215-1224. ISSN 0271-678X (doi:10.1038/jcbfm.2013.70)

2012

Ord, E.N.J., Shirley, R., van Kralingen, J.C., Graves, A., McClure, J.D., Wilkinson, M., McCabe, C., Macrae, I.M., and Work, L.M. (2012) Positive impact of pre-stroke surgery on survival following transient focal ischemia in hypertensive rats. Journal of Neuroscience Methods, 211 (2). pp. 305-308. ISSN 0165-0270 (doi:10.1016/j.jneumeth.2012.09.001)

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

2010

Greig, J.A., Shirley, R., Graham, D., Denby, L., Dominiczak, A.F., Work, L.M., and Baker, A. (2010) Vascular-targeting anti-oxidant therapy in a model of hypertension and stroke. Journal of Cardiovascular Pharmacology, 56 (6). pp. 642-650. ISSN 0160-2446 (doi:10.1097/FJC.0b013e3181f8f19f)

Greig, J.A., Shirley, R., Graham, D., Denby, L., Dominiczak, A.F., Work, L.M., and Baker, A.H. (2010) Vascular-Targeting Antioxidant Therapy in a Model of Hypertension and Stroke. Journal of Cardiovascular Pharmacology, 56 (6). pp. 642-650. ISSN 0160-2446 (doi:10.1097/FJC.0b013e3181f8f19f)

2009

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)

2008

Graham, T, McIntosh, JB, Work, LM, Nathwani, A, and Baker, AH (2008) Performance of AAV8 vectors expressing human factor IX from a hepatic-selective promoter following intravenous injection into rats. Genetic Vaccines and Therapy, 6 (1). p. 9. ISSN 1479-0556 (doi:10.1186/1479-0556-6-9)

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)

2007

Baker, AH et al. (2007) Brain protection using autologous bone marrow cell, metalloproteinase inhibitors, and metabolic treatment in cerebral ischemia. Proceedings of the National Academy of Sciences of the United States of America, 104 . pp. 3597-3602. (doi:10.1073/pnas.0611112104)

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)

2006

Perabo, L et al. (2006) Heparan sulfate proteoglycan binding properties of adeno-associated virus retargeting mutants and consequences for their in vivo tropism. Journal of Virology, 80 . pp. 7265-7269. ISSN 0022-538X (doi:10.1128/JVI.00076-06)

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)

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

Work, L.M., Nicol, C.G., Denby, L., and Baker, A.H. (2004) In vivo biopanning: a methodological approach to identifying novel targeting ligands for delivery of biological agents to the vasculature. In: Fennell, J.P. and Baker, A.H. (eds.) Hypertension: Methods and Protocols. Series: Methods in molecular medicine (108). Humana Press, Totowa, NJ, USA, pp. 395-413. ISBN 9781588293237

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

Baker, AH, Denby, L, Dishart, KL, and Work, LM (2003) Gene therapy for cardiovascular disease. Journal of Biomedicine and Biotechnology . pp. 138-148.

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.

2001

McPhaden, AR, Pyne, NJ, Pyne, S, Wadsworth, RM, Wainwright, CL, and Work, LM (2001) Short-term local delivery of an inhibitor of ras farnesyltransferase prevents neointima formation in vivo after porcine coronary balloon angioplasty. Circulation, 104 (13). pp. 1538-1543.

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)

This list was generated on Tue Oct 1 21:08:12 2013 BST.
Jump to: Article | Book Section
Number of items: 25.

Article

Ord, E.N.J., Shirley, R., McClure, J.D., McCabe, C., Kremer, E.J., Macrae, I.M., and Work, L.M. (2013) Combined antiapoptotic and antioxidant approach to acute neuroprotection for stroke in hypertensive rats. Journal of Cerebral Blood Flow and Metabolism, 33 (8). pp. 1215-1224. ISSN 0271-678X (doi:10.1038/jcbfm.2013.70)

Ord, E.N.J., Shirley, R., van Kralingen, J.C., Graves, A., McClure, J.D., Wilkinson, M., McCabe, C., Macrae, I.M., and Work, L.M. (2012) Positive impact of pre-stroke surgery on survival following transient focal ischemia in hypertensive rats. Journal of Neuroscience Methods, 211 (2). pp. 305-308. ISSN 0165-0270 (doi:10.1016/j.jneumeth.2012.09.001)

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

Greig, J.A., Shirley, R., Graham, D., Denby, L., Dominiczak, A.F., Work, L.M., and Baker, A. (2010) Vascular-targeting anti-oxidant therapy in a model of hypertension and stroke. Journal of Cardiovascular Pharmacology, 56 (6). pp. 642-650. ISSN 0160-2446 (doi:10.1097/FJC.0b013e3181f8f19f)

Greig, J.A., Shirley, R., Graham, D., Denby, L., Dominiczak, A.F., Work, L.M., and Baker, A.H. (2010) Vascular-Targeting Antioxidant Therapy in a Model of Hypertension and Stroke. Journal of Cardiovascular Pharmacology, 56 (6). pp. 642-650. ISSN 0160-2446 (doi:10.1097/FJC.0b013e3181f8f19f)

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)

Graham, T, McIntosh, JB, Work, LM, Nathwani, A, and Baker, AH (2008) Performance of AAV8 vectors expressing human factor IX from a hepatic-selective promoter following intravenous injection into rats. Genetic Vaccines and Therapy, 6 (1). p. 9. ISSN 1479-0556 (doi:10.1186/1479-0556-6-9)

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)

Baker, AH et al. (2007) Brain protection using autologous bone marrow cell, metalloproteinase inhibitors, and metabolic treatment in cerebral ischemia. Proceedings of the National Academy of Sciences of the United States of America, 104 . pp. 3597-3602. (doi:10.1073/pnas.0611112104)

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)

Perabo, L et al. (2006) Heparan sulfate proteoglycan binding properties of adeno-associated virus retargeting mutants and consequences for their in vivo tropism. Journal of Virology, 80 . pp. 7265-7269. ISSN 0022-538X (doi:10.1128/JVI.00076-06)

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)

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)

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.

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

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)

Baker, AH, Denby, L, Dishart, KL, and Work, LM (2003) Gene therapy for cardiovascular disease. Journal of Biomedicine and Biotechnology . pp. 138-148.

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

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.

McPhaden, AR, Pyne, NJ, Pyne, S, Wadsworth, RM, Wainwright, CL, and Work, LM (2001) Short-term local delivery of an inhibitor of ras farnesyltransferase prevents neointima formation in vivo after porcine coronary balloon angioplasty. Circulation, 104 (13). pp. 1538-1543.

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)

Book Section

Work, L.M., Nicol, C.G., Denby, L., and Baker, A.H. (2004) In vivo biopanning: a methodological approach to identifying novel targeting ligands for delivery of biological agents to the vasculature. In: Fennell, J.P. and Baker, A.H. (eds.) Hypertension: Methods and Protocols. Series: Methods in molecular medicine (108). Humana Press, Totowa, NJ, USA, pp. 395-413. ISBN 9781588293237

This list was generated on Tue Oct 1 21:08:12 2013 BST.

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

  • Modulation of miRNA as a therapeutic strategy for stroke
    Medical Research Council
    2012 - 2015
     
  • Supporting the ischaemic brain with oxygen-carrying perfluorocarbons.
    Scottish Executive Health Department
    2012 - 2013
     
  • A combined approach targeting oxidative stress and apoptosis in stroke
    British Heart Foundation
    2008 - 2012
     
  • A combined approach to target reactive oxygen species and neuronal death in stroke
    British Heart Foundation
    2007 - 2010