Gould, David

David Gould

Honorary Lecturer

Graduated from Sunderland Polytechnic with a degree in Pharmacology and was awarded with a PhD in Immunopharmacology from Southampton University. Became a postdoctoral researcher at the Kennedy Institute of Rheumatology in 1994 and later at the William Harvey Research Institute from 1999 and was later appointed as an honorary lecturer. Research achievements have included the development of self-contained pharmacologically regulated gene therapy vectors; construction of promoters with cell specific activity; development of hybrid promoters responsive to pharmacological and physiological regulation; monitoring of gene expression and labeled cells by real-time bioluminescent imaging.

Summary of Research

I have a keen interest in the development of gene based or genetically engineered treatments for disease. I have made progress in developing gene therapy vectors that permit controlled expression of a therapeutic gene by utilising the tetracycline system of gene expression. In order to develop this system towards clinical application it is necessary to prevent immunogenicity of the regulatory proteins and develop improved methods for gene delivery suitable for clinical application. To avoid immunogenicity we are examining both modification of regulatory proteins with stabilisation elements and de-targeting their expression from immune cells.  As an approach to improve delivery of genes collaborative studies with Prof Gleb Sukhorukov (SEMS) have been aimed at utilising nanoengineered layer-by-layer assembled microparticles that have the potential to be multifunctionalised.

Gene therapies could also offer improved and innovative approaches to disease treatment through both local production and linking expression levels of therapeutic molecules to degree of disease activity. Through gene delivery to cells at a disease site it is then possible to produce therapeutic molecules at their site of action which can potentially limit side effects associated with systemic delivery of the same therapeutic molecules. Cellular ‘sensing’ in engineered cells at the disease site could also be harnessed to control production of therapeutic molecules via transcriptional and post transcriptional control.

Monitoring microcapsule delivery to cells using real-time bioluminescent imaging
Monitoring microcapsule delivery to cells using real-time bioluminescent imaging

Members of the Group

PhD students: Hodan Mohamed; Hawzheen Muhammad

Key Publications

For a full list of publist publications click here

Pavlov, A. M., Sukhorukov, G. B., and Gould, D. J. (2013) Lessons in Microcapsule Assembly from Imaging Delivery of a Bioluminescent Enzyme. Biomacromolecules 14, 608-612. DOI: 10.1021/bm3019054

Viale, D. L., Cafferata, E. G., Gould, D., Rotondaro, C., Chernajovsky, Y., Curiel, D. T., Podhajcer, O. L., and Lopez, M. V. (2013) Therapeutic Improvement of a Stroma-Targeted CRAd by Incorporating Motives Responsive to the Melanoma Microenvironment. J Invest Dermatol, DOI: 10.1038/jid.2013.191

 Mullen, L., Adams, G., Foster, J., Vessillier, S., Koster, M., Hauser, H., Layward, L., Gould, D., and Chernajovsky, Y. (2013) A comparative study of matrix metalloproteinase and aggrecanase mediated release of latent cytokines at arthritic joints. Ann Rheum Dis. DOI: 10.1136/annrheumdis-2013-203513

Gould, D. (2013) Gene doping: gene delivery for olympic victory. British journal of clinical pharmacology 76, 292-298. DOI: 10.1111/bcp.12010

Pavlov, A. M., Sukhorukov, G. B., and Gould, D. J. (2013) Location of molecules in layer-by-layer assembled microcapsules influences activity, cell delivery and susceptibility to enzyme degradation. J Control Release 172, 22-29. DOI: 10.1016/j.jconrel.2013.08.002

Mullen, L., Rigby, A., Sclanders, M., Adams, G., Mittal, G., Colston, J., Fatah, R., Subang, C., Foster, J., Francis-West, P., Koster, M., Hauser, H., Layward, L., Vessillier, S., Annenkov, A., Al-Izki, S., Pryce, G., Bolton, C., Baker, D., Gould, D., and Chernajovsky, Y. (2013) Latency can be conferred to a variety of cytokines by fusion with latency associated peptide from TGF-b. Expert Opin Drug Deliv (in press)

Koutsokeras, A., Purkayashta, N., Rigby, A., Subang, M., Sclanders, M., Vessillier, S., Mullen, L., Chernajovsky, Y., and Gould, D. (2013) Generation of an efficiently secreted, cell penetrating NF-kB inhibitor. Faseb J (in press)

The inflammatory cytokine TNF-? generates an autocrine tumor-promoting network in epithelial ovarian cancer cells. Kulbe H, Thompson R, Wilson J, Robinson S, Hagemann T, Fatah R, Gould D, Ayhan A, Balkwill F.  Cancer Res. 2007, 67:585-92.

Gene therapy with an improved doxycycline regulated plasmid encoding a TNF? inhibitor in experimental arthritis. Gould D, Yousaf N, Fatah R, Subang MC, Chernajovsky Y. Arthritis Res Ther. 2007,9:R7. 

Reduction of arthritis following intra-articular administration of an adeno-associated virus serotype 5 expressing a disease-inducible TNF? blocking agent. Adriaansen J, Khoury M, de Cortie CJ, Fallaux FJ, Bigey P, Scherman D, Gould D, Chernajovsky Y, Apparailly F, Jorgensen C, Vervoordeldonk MJBM, Tak PP. Ann Rheum Dis. 2007, 66:1143-50.

Inflammation-inducible anti-TNF gene expression mediated by intra-articular injection of serotype 5 adeno-associated virus reduces arthritis. Khoury M, Adriaansen J, Vervoordeldonk MJ, Gould D, Chernajovsky Y, Bigey P, Bloquel C, Scherman D, Tak PP, Jorgensen C, Apparailly F. J Gene Med. 2007, 9:596-604.

Novel delivery methods to achieve immunomodulation. Gould D, Chernajovsky Y.  Curr Opin Pharmacol. 2007, 7:445-50

Biodistribution, long term survival and safety of human adipose tissue derived mesenchymal stem cells in nude mice by non-invasive bioluminescence imaging. Vilalta M, Dégano IR, Bagó J, Gould D, Santos M, García-Arranz M, Ayats R,  Fuster C, Chernajovsky Y, García-Olmo D, Rubio N,  Blanco J. Stem Cells Dev. 2008; 17:993-1003.

Repopulation of B-lymphocytes with restricted gene expression using haematopoietic stem cells engineered with lentiviral vectors. Taher TE, Tulone R, Fatah R, D’Acquisto F, Gould D, and Mageed RA. Gene Therapy, 2008, 15:998-1006

Tumor associated stromal cells play a critical role on the outcome of the oncolytic efficacy of conditionally replicative adenoviruses. Lopez MV, Viale DL, Cafferata EG, Bravo AI, Carbone C, Gould D, Chernajovsky Y, Podhajcer OL. PLoS ONE. 2009;4(4):e5119.

Dual luciferase labelling for non-invasive bioluminescence imaging of mesenchymal stromal cell chondrogenic differentiation in demineralized bone matrix scaffolds. Vilalta M, Jorgensen C, Dégano IR, Chernajovsky Y, Gould D, Noël D, Andrades JA, Becerra J, Rubio N, Blanco J. Biomaterials. 2009;30:4986-95.

Quantitative imaging of cartilage and bone for morphological assessment of gene therapy approaches in experimental arthritis. Stok KS, Noël D, Apparailly F, Gould D, Chernajovsky Y, Jorgensen C, Müller R., J Tissue Eng Regen Med. 2010;4:387-94.

Human single chain fragment variable (scFv) that specifically targets arthritic cartilage. Hughes C, Faurholm B, Dell'accio F, Manzo A, Seed M, Eltawil N, Marrelli A, Gould D, Subang C, Al-Kashi A, De Bari C, Winyard P, Chernajovsky Y, Nissim A. Arthritis Rheum. 2010; 62:1007-16.

A novel hybrid promoter responsive to pathophysiological and pharmacological regulation. Subang MC, Fatah R, Bright C, Blanco P, Berenstein M, Wu Y, Podhajcer O, Winyard PG, Chernajovsky Y, Gould D. J Mol Med (Berl). 2011 Oct 30. [Epub ahead of print].

Gene Doping: Olympic Genes for Olympic Dreams. Battery L, Solomon A, Gould D. J R Soc Med. 2011;104:494-500.

The Peritoneal Microenvironment of high-grade serous ovarian cancer. Leinster DA, Kulbe H, Everitt G, Thompson R, Perretti M, Gavins F, Cooper D, Gould D, Ennis DP, Lockley M, McNeish IA, Nourshargh S,  Balkwill FR. J. Pathol. 2012.

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