Dr Lorraine Work

  • Senior Lecturer (Institute of Cardiovascular and Medical Sciences)
  • Associate (School of Medicine, Dentistry and Nursing)

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

Biography

I graduated from the University of Strathclyde with a 1st class BSc (Hons) in Immunology & Pharmacology in 1995 and went on to study for my PhD investigating anti-proliferative agents for therapy in in vitro and in vivo models of vascular injury, graduating in 1999.  Following a brief period spent at the University of Washington, Seattle, I joined the Division of Cardiovascular and Medical Science, University of Glasgow in 2000 as a post-doctoral researcher in Professor A. Baker’s research group.  In so doing I moved from pharmacological interventions to gene based approaches - specifically, identifying novel targets which could be used to direct therapy to the vasculature (smooth muscle cells and organ specific endothelial beds).  I was awarded a BHF Intermediate Research Fellowship in 2006 to study a combination of pharmacological and gene-based therapies in stroke.  In 2007, I was appointed lecturer through the BBSRC Capacity Building awards in Integrative Mammalian Biology (IMB) and so central to my research is the translation of knowledge gained from single molecules back to the whole organism, including in vivo studies.  In 2015 I was promoted to Senior Lecturer.

Research interests

Member: Stroke Research

My interest lies in combining gene and drug intervention strategies in an attempt to reduce infarct volume and improve neurological recovery following experimental stroke.  I am interested in the use of microRNAs as potential means of delivering a single therapy to achieve a multifactorial outcome with endogenous extracellular vesicles being used as a means of delivery.  Furthermore, I have an interest in determining the effect of stabilisation of mitochondrial function on outcome following stroke, how endogenous mitochondrial turnover processes are altered with ischaemic injury and targeting mitochondria therapeutically.  Although stroke is the 3rd leading cause of death and the leading cause of long term disability worldwide there is, currently, only one clinically approved intervention.  In determining the relative contribution of the underlying signalling pathways to infarct size and consequent neurological recovery we hope to identify novel therapeutic approaches.  Furthermore, many target microRNAs may be involved in promoting endogenous repair allowing delayed delivery thus promoting clinical translation.  My research group use in vitro methods to determine efficacy prior to in vivo application in a model of transient cerebral ischaemia.  

Research:

Grants

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

  • Refinement in pre-clinical stroke research: investigation of morbidity and mortality and development of improved post-stroke care in rodents
    American College of Laboratory
    2015 - 2016
     
  • Angiotensin-(1-7): a novel treatment for acute and long term recovery from stroke?
    The Henry Smith Charity
    2014 - 2016
     
  • Modulation of the kynurenic pathway following stroke (ISSF STS)
    Wellcome Trust
    2013 - 2014
     
  • 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 - 2014
     
  • 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
     

Teaching

I successfully completed my PG Cert in Academic Practice becoming a Fellow of the Higher Education Academy in 2009.  Currently, I lecture for the MSc Cardiovascular Sciences and to levels 2, 3 and 4 for the Human Biology degree groups.  I am a PBL facilitator for undergraduate medical students (years 1 and/or year 2).  A significant portion of my teaching time is spent on project supervision and assessment for wet laboratory-based projects for L4 students (Pharmacology, Neuroscience), intercalating BMed Sci students and MRes/MSc students (IMB/Systems Biology and Clinical Pharmacology).  Further to assessment of the research project write up/students laboratory performance, I have completed the oral "viva" style exam and assessed the oral presentations.  I am course co-ordinator for the IMB specialisation within the MRes in Biomedical Sciences.  I established and run a 5 day summer school in “in vivo cardiovascular systems”.  As course leader this involved a substantial amount of coordination/planning with the involvement of academic staff from the Universities of Glasgow and Strathclyde.  Each day had to be meticulously planned, equipment sourced, checked and support staff identified and trained.  There was a significant amount of setup for the in vivo experiments and validation of equipment prior to the summer school.  All of this had to be done within a set budget.  This highly innovative learning experience was a tremendous success, measured by the extremely positive feedback left by participants annually.  Based on the success of the schools, further funding was secured to allow the schools to continue and I remain integrally involved with these both directly and as the project licence holder.

Publications

List by: Type | Date

Jump to: 2016 | 2015 | 2014 | 2013 | 2012 | 2010 | 2009 | 2008 | 2007 | 2006 | 2005 | 2004 | 2003 | 2002 | 2001 | 1998
Number of items: 30.

2016

Chouchani, E. T., Pell, V. R., James, A. M., Work, L. M. , Saeb-Parsy, K., Frezza, C., Krieg, T. and Murphy, M. P. (2016) A unifying mechanism for mitochondrial superoxide production during ischemia-reperfusion injury. Cell Metabolism, 23(2), pp. 254-263. (doi:10.1016/j.cmet.2015.12.009) (PMID:26777689)

2015

Akehurst, C. et al. (2015) Differential expression of microRNA-206 and its target genes in pre-eclampsia. Journal of Hypertension, 33(10), pp. 2068-2074. (doi:10.1097/HJH.0000000000000656) (PMID:26213997) (PMCID:PMC4570688)

2014

Chouchani, E. T. et al. (2014) Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature, 515(7527), pp. 431-435. (doi:10.1038/nature13909) (PMID:25383517) (PMCID:PMC4255242)

Shirley, R., Ord, E. N.J. and Work, L. M. (2014) Oxidative stress and the use of antioxidants in stroke. Antioxidants, 3(3), pp. 472-501. (doi:10.3390/antiox3030472)

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. (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. (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. (doi:10.1161/HYPERTENSIONAHA.111.177485)

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. (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. (doi:10.1016/j.febslet.2009.05.037)

Work, L.M., Dominiczak, A.F. and McBride, M.W. (2009) The genetic basis of stroke: animal models. In: 3rd Report on Stroke: Genetic research in prevention and in cure. Il Pensiero Scientifico Editore, pp. 219-40.

2008

Graham, T., McIntosh, J., Work, L., Nathwani, A. and Baker, A. (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. (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. (doi:10.1038/sj.gt.3303077)

2007

Kritz, A. B., Nicol, C. G., Dishart, K. L., Nelson, R., Holbeck, S., Von Seggern, D. J., Work, L. M., Mcvey, J. H., Nicklin, S. A. and Baker, A. H. (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)

Baker, A.H. 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. (doi:10.1038/sj.mt.6300214)

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(14), pp. 7265-7269. (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, A., Kritz, A., Work, L., Nicklin, S. and Nicklin, A. (2005) Cell-selective viral gene delivery vectors for the vasculature. Experimental Physiology, 90(1), pp. 27-31. (doi:10.1113/expphysiol.2004.028126)

2004

Work, L.M., Reynolds, P. N. and Baker, A. H. (2004) Improved gene delivery to human saphenous vein cells and tissue using a peptide-modified adenoviral vector. Genetic Vaccines and Therapy, 2(1), p. 14. (doi:10.1186/1479-0556-2-14)

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.

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 (doi:10.1385/1-59259-850-1:395)

Work, L., Nicklin, S., Brain, N., Dishart, K., Von Seggern, D., Hallek, M., Buning, H. and Baker, A. (2004) Development of efficient viral vectors selective for vascular smooth muscle cells. Molecular Therapy, 9(2), pp. 198-208. (doi:10.1016/j.ymthe.2003.11.006)

Work, L., Ritchie, N., Nicklin, S., Reynolds, P. and Baker, A. (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

Dishart, K.L., Work, L.M., Denby, L. and Baker, A.H. (2003) Gene therapy for cardiovascular disease. Journal of Biomedicine and Biotechnology, 2003(2), pp. 138-148. (doi:10.1155/S1110724303209086)

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

2002

Wainwright, C.L., Miller, A.M., Work, L.M. and Del Soldato, P. (2002) NCX4016 (NO-aspirin) reduces infarct size and suppresses arrhythmias following myocardial ischaemia/reperfusion in pigs. British Journal of Pharmacology, 135(8), pp. 1882-1888. (doi:10.1038/sj.bjp.0704646)

Work, L. M., Nicklin, S. A., White, S. J. and Baker, A. H. (2002) Use of phage display to identify novel peptides for targeted gene therapy. In: Phillips, M. I. (ed.) Gene Therapy Methods. Series: Methods in enzymology (346). Academic Press: San Diego, California ; London, pp. 157-176. ISBN 9780121822477 (doi:10.1016/S0076-6879(02)46055-7)

2001

Work, L.M., McPhaden, A.R., Pyne, N.J., Pyne, S., Wadsworth, R.M. and Wainwright, C.L. (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. (doi:10.1161/​hc3801.095661)

Nicklin, S., Von Seggern, D., Work, L., Pek, D., Dominiczak, A., Nemerow, G. and Baker, A. (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(6), pp. 534-542. (doi:10.1006/mthe.2001.0489)

1998

Kennedy, S., Work, L., Ferris, P., Miller, A.M., McManus, B., Wadsworth, R.M. and Wainwright, C.L. (1998) Role of nitric oxide and free radicals in the contractile response to non-preactivated leukocytes. European Journal of Pharmacology, 345(3), pp. 269-277. (doi:10.1016/S0014-2999(98)00007-7)

This list was generated on Sat Jun 24 20:29:31 2017 BST.
Number of items: 30.

Articles

Chouchani, E. T., Pell, V. R., James, A. M., Work, L. M. , Saeb-Parsy, K., Frezza, C., Krieg, T. and Murphy, M. P. (2016) A unifying mechanism for mitochondrial superoxide production during ischemia-reperfusion injury. Cell Metabolism, 23(2), pp. 254-263. (doi:10.1016/j.cmet.2015.12.009) (PMID:26777689)

Akehurst, C. et al. (2015) Differential expression of microRNA-206 and its target genes in pre-eclampsia. Journal of Hypertension, 33(10), pp. 2068-2074. (doi:10.1097/HJH.0000000000000656) (PMID:26213997) (PMCID:PMC4570688)

Chouchani, E. T. et al. (2014) Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature, 515(7527), pp. 431-435. (doi:10.1038/nature13909) (PMID:25383517) (PMCID:PMC4255242)

Shirley, R., Ord, E. N.J. and Work, L. M. (2014) Oxidative stress and the use of antioxidants in stroke. Antioxidants, 3(3), pp. 472-501. (doi:10.3390/antiox3030472)

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. (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. (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. (doi:10.1161/HYPERTENSIONAHA.111.177485)

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. (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. (doi:10.1016/j.febslet.2009.05.037)

Graham, T., McIntosh, J., Work, L., Nathwani, A. and Baker, A. (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. (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. (doi:10.1038/sj.gt.3303077)

Kritz, A. B., Nicol, C. G., Dishart, K. L., Nelson, R., Holbeck, S., Von Seggern, D. J., Work, L. M., Mcvey, J. H., Nicklin, S. A. and Baker, A. H. (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)

Baker, A.H. 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. (doi:10.1038/sj.mt.6300214)

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(14), pp. 7265-7269. (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, A., Kritz, A., Work, L., Nicklin, S. and Nicklin, A. (2005) Cell-selective viral gene delivery vectors for the vasculature. Experimental Physiology, 90(1), pp. 27-31. (doi:10.1113/expphysiol.2004.028126)

Work, L.M., Reynolds, P. N. and Baker, A. H. (2004) Improved gene delivery to human saphenous vein cells and tissue using a peptide-modified adenoviral vector. Genetic Vaccines and Therapy, 2(1), p. 14. (doi:10.1186/1479-0556-2-14)

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.

Work, L., Nicklin, S., Brain, N., Dishart, K., Von Seggern, D., Hallek, M., Buning, H. and Baker, A. (2004) Development of efficient viral vectors selective for vascular smooth muscle cells. Molecular Therapy, 9(2), pp. 198-208. (doi:10.1016/j.ymthe.2003.11.006)

Work, L., Ritchie, N., Nicklin, S., Reynolds, P. and Baker, A. (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)

Dishart, K.L., Work, L.M., Denby, L. and Baker, A.H. (2003) Gene therapy for cardiovascular disease. Journal of Biomedicine and Biotechnology, 2003(2), pp. 138-148. (doi:10.1155/S1110724303209086)

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

Wainwright, C.L., Miller, A.M., Work, L.M. and Del Soldato, P. (2002) NCX4016 (NO-aspirin) reduces infarct size and suppresses arrhythmias following myocardial ischaemia/reperfusion in pigs. British Journal of Pharmacology, 135(8), pp. 1882-1888. (doi:10.1038/sj.bjp.0704646)

Work, L.M., McPhaden, A.R., Pyne, N.J., Pyne, S., Wadsworth, R.M. and Wainwright, C.L. (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. (doi:10.1161/​hc3801.095661)

Nicklin, S., Von Seggern, D., Work, L., Pek, D., Dominiczak, A., Nemerow, G. and Baker, A. (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(6), pp. 534-542. (doi:10.1006/mthe.2001.0489)

Kennedy, S., Work, L., Ferris, P., Miller, A.M., McManus, B., Wadsworth, R.M. and Wainwright, C.L. (1998) Role of nitric oxide and free radicals in the contractile response to non-preactivated leukocytes. European Journal of Pharmacology, 345(3), pp. 269-277. (doi:10.1016/S0014-2999(98)00007-7)

Book Sections

Work, L.M., Dominiczak, A.F. and McBride, M.W. (2009) The genetic basis of stroke: animal models. In: 3rd Report on Stroke: Genetic research in prevention and in cure. Il Pensiero Scientifico Editore, pp. 219-40.

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 (doi:10.1385/1-59259-850-1:395)

Work, L. M., Nicklin, S. A., White, S. J. and Baker, A. H. (2002) Use of phage display to identify novel peptides for targeted gene therapy. In: Phillips, M. I. (ed.) Gene Therapy Methods. Series: Methods in enzymology (346). Academic Press: San Diego, California ; London, pp. 157-176. ISBN 9780121822477 (doi:10.1016/S0076-6879(02)46055-7)

This list was generated on Sat Jun 24 20:29:31 2017 BST.