HomeContact Details:
Tristan McKay obtained his Bachelors degree from University of Essex, a Master’s degree from Imperial College and graduated with a Ph.D from Imperial College in 2000 having developed new gene therapy approaches to the hepatobiliary manifestations of Cystic Fibrosis (CF). He went on to gain post-doctoral experience at the internationally renowned Cystic Fibrosis Research & Treatment Center, University of North Carolina applying lentiviral-based gene therapy to pulmonary models of CF. Dr. McKay returned to the UK as Group Leader of the Gene Therapy group, a component of the multidisciplinary UK Centre for Tissue Engineering (UKCTE) based at the Universities of Manchester and Liverpool. This led to him focussing on gene transfer in stem cells, most particularly Embryonic Stem (ES) cells and latterly the genetic reprogramming of somatic cells to induced Pluripotent Stem (iPS) cells at the North West Embryonic Stem Cell Centre (NWESCC), University of Manchester. In 2010, Dr. McKay took up the position of Lecturer in Stem Cell Biology within the Centre for Endocrinology, WHRI to apply iPS technology to generate models of disease in Endocrinology and specifically Lipid Diseases.
Current research interests:
Mechanism of iPS reprogramming
The ability to genetically reprogramme human somatic cells (such as a skin cell) to stem cells with the ability to differentiate into virtually any cell in the human body (induced Pluripotent Stem or “iPS” cells) has created huge potential for the study and treatment of a myriad of debilitating diseases such as diabetes, Alzheimer’s, osteoarthritis, cardiovascular and liver disease. Currently, the mode of genetic manipulation to affect iPS reprogramming is highly inefficient and not clinically efficacious. I am currently studying the role of a family of small RNAs called microRNAs in iPS reprogramming using an established cell model. The aim is to elucidate novel mechanisms involved in iPS reprogramming in order to increase efficiency and move toward transient processes of genetic manipulation that are safer and more efficacious in generating iPS for disease modelling and therapy.
Genetic reporters of differentiation & disease in cells
The processes of cellular differentiation and disease induction are led and controlled by gene expression. I am developing a range of technologies to quantitate genetic changes at the cellular, tissue and whole body level in real time. Either fluorescent or bioluminescent genes driven by gene promoters that are activated by the progression of differentiation or disease are used to act as quantitative reporters. I am applying viral vector and zinc finger nuclease (ZFN) technologies to insert these genetic elements into ES/iPS cells as well as whole body systems.
Targeted differentiation of pluripotent stem cells to functional hepatocytes
We aim to generate repeatable protocols for the differentiation of hepatocytes (liver cells) from pluripotent stem cells (ES/iPS). Human hepatocytes are challenging to obtain and virtually impossible to maintain in culture. We will produce iPS cells from patients with diseases of lipid metabolism and then differentiate these into hepatocytes to study cellular mechanisms of disease.
Key publications
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Waddington, S.N., Crossley, R., Sheard, V., Howe, S.J., Buckley, S.M., Coughlan, L., Gilham, D.E., Hawkins, R.E., and McKay, T.R. (2010). Gene Delivery of a Mutant TGFbeta3 Reduces Markers of Scar Tissue Formation After Cutaneous Wounding. Mol Ther.
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Rothwell, D.G., Crossley, R., Bridgeman, J.S., Sheard, V., Zhang, Y., Sharp, T., Hawkins, R.E., Gilham, D., and McKay, T.R. (2010). Functional expression of secreted proteins from a bicistronic retroviral cassette based on FMDV 2A can be position-dependent. Hum Gene Ther.
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Camarasa, M.V., Kerr, R.W., Sneddon, S.F., Bates, N., Shaw, L., Oldershaw, R.A., Small, F., Baxter, M.A., McKay, T.R., Brison, D.R., et al. (2010). Derivation of Man-1 and Man-2 research grade human embryonic stem cell lines. In Vitro Cell Dev Biol Anim 46, 386-394.
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Tew, S.R., Peffers, M.J., McKay, T.R., Lowe, E.T., Khan, W.S., Hardingham, T.E., and Clegg, P.D. (2009). Hyperosmolarity regulates SOX9 mRNA posttranscriptionally in human articular chondrocytes. Am J Physiol Cell Physiol 297, C898-906.
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Oldershaw, R.A., Tew, S.R., Russell, A.M., Meade, K., Hawkins, R., McKay, T.R., Brennan, K.R., and Hardingham, T.E. (2008). Notch signaling through Jagged-1 is necessary to initiate chondrogenesis in human bone marrow stromal cells but must be switched off to complete chondrogenesis. Stem Cells 26, 666-674.
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Buckley, S.M., Howe, S.J., Rahim, A.A., Buning, H., McIntosh, J., Wong, S.P., Baker, A.H., Nathwani, A., Thrasher, A.J., Coutelle, C., McKay, T.R. and Waddington, S.N. (2008a). Luciferin detection after intranasal vector delivery is improved by intranasal rather than intraperitoneal luciferin administration. Hum Gene Ther 19, 1050-1056.
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Buckley, S.M., Howe, S.J., Sheard, V., Ward, N.J., Coutelle, C., Thrasher, A.J., Waddington, S.N., and McKay, T.R. (2008b). Lentiviral transduction of the murine lung provides efficient pseudotype and developmental stage-dependent cell-specific transgene expression. Gene Ther 15, 1167-1175.
