- 200 years
- Study
- International
- Business and employers
- Research
- About us
https://webcdn.mmu.ac.uk/profiles/img/profile-images/T-McKay-250x250-crop-145x145-5d8c7a7b936b3.jpg
Stem cell biology
External Advisor: Alicia Roig-Merino Thesis Advisory Committee, DKFZ Cancer Institute, Heidelberg, Germany.
Advisor to William Harvey iPSC Centre.
Grant Reviewer: Wellcome, BBSRC, MRC, Action Medical Research.
Genetic Modification advisor to Cellular Therapeutics.
Manuscript Reviewer for multiple journals including Stem Cells.
The McKay group have established expertise in generating induced pluripotent stem cells (iPSC) from mouse and human somatic cells. We use this platform technology to study both reprogramming to pluripotency and neural differentiation at the molecular level.
Induced Pluripotency - We apply lentiviral technology to stably introduce synthetic transcription factor activated reporter gene cassettes into somatic cells in order to evaluate their activity during iPSC reprogramming in living cells. This has led us to new insights into the way a cell switches the manner in which it produces energy during iPSC reprogramming.
Neural Differentiation - We apply state of the art technologies to interrogate the cell signaling underlying neural differentiation during normal development and in neuronopathic disease.
Collaborators
Prof. Simon Waddington (UCL) - In vivo disease modeling.
Dr. Ahad Rahim (UCL) - In vivo models of neurodegeneration. Prof. Michael Duchen (UCL) - Mitochondrial Biology
Prof. Sara Mole (UCL) - In vitro models of neurodegeneration.
Pluripotent stem cells such as embryonic stem cells (ESC) have the virtually limitless capacity to self-renew whilst retaining an ability to differentiate into any cell type within the human body. This means that they hold great promise as a cellular source for regenerative medicine therapies. Consequently the pluripotent state and subsequent differentiation is well studied.
An alternative source of pluripotent stem cells are induced pluripotent stem cells (iPSC) whereby the forced expression of 4 critical genes in a somatic cell can result in de-differentiation to pluripotency. For cells to undergo this remarkable journey, effectively reversing development, fundamental changes must occur at the gene expression, epigenetic and metabolic levels. Little is known about the chronology of these changes and whether this is a loosely random process or an ordered series of events. The research of my group is focussed on understanding the order of events during iPSC reprogramming.
Human iPSC represent a powerful resource for in vitro disease modeling, developing personalised medicines and potential cell therapies. iPSC lines can be generated from patients by reprogramming cells isolated from a blood sample or a small skin biopsy. This cell platform has provided new insights into neurodegenerative diseases such as Parkinson’s and Alzheimer’s disease. My group is interested in the molecular regulators of neural differentiation and their relationship to processes that result in neural degeneration, ageing and dementia.
CA. Vink, JR. Counsell, DP. Perocheau, R. Karda, SMK. Buckley, et al. MH. Brugman, M. Galla, A. Schambach, TR. McKay, SN. Waddington, SJ. Howe. (2017). Eliminating HIV-1 Packaging Sequences from Lentiviral Vector Proviruses Enhances Safety and Expedites Gene Transfer for Gene Therapy. Molecular Therapy. 25(8), pp.1790-1804.
AM. Sharaireh, LM. Fitzpatrick, CM. Ward, TR. McKay, RD. Unwin (2020). Epithelial cadherin regulates transition between the naïve and primed pluripotent states in mouse embryonic stem cells. Stem Cells. 38(10), pp.1292-1306.
JM. Delhove, R. Karda, LM. FitzPatrick, SMK. Buckley, SN. Waddington, et al. TR. McKay. (2020). Non-invasive somatotransgenic bioimaging in living animals. F1000Research. 9, pp.1216-1216.
JA. Diaz, A. Geard, LM. FitzPatrick, JMKM. Delhove, SMK. Buckley, et al. SN. Waddington, TR. McKay, R. Karda. (2020). Continual Conscious Bioluminescent Imaging in Freely Moving Mice. Methods Mol Biol. 2081, pp.161-175.
SA. Smith, RB. Sessions, DK. Shoemark, C. Williams, R. Ebrahimighaei, et al. MC. McNeill, MP. Crump, TR. McKay, G. Harris, AC. Newby, M. Bond. (2019). Antiproliferative and Antimigratory Effects of a Novel YAP-TEAD Interaction Inhibitor Identified Using in Silico Molecular Docking. Journal of Medicinal Chemistry. 62(3), pp.1291-1305.
DE. Foxler, KS. Bridge, JG. Foster, P. Grevitt, S. Curry, et al. KM. Shah, KM. Davidson, A. Nagano, E. Gadaleta, HI. Rhys, PT. Kennedy, MA. Hermida, T-Y. Chang, PE. Shaw, LE. Reynolds, TR. McKay, H-W. Wang, PS. Ribeiro, MJ. Plevin, D. Lagos, NR. Lemoine, P. Rajan, TA. Graham, C. Chelala, KM. Hodivala-Dilke, I. Spendlove, TV. Sharp. (2018). A HIF-LIMD1 negative feedback mechanism mitigates the pro-tumorigenic effects of hypoxia. EMBO molecular medicine. 10(8), pp.1-18.
LM. FitzPatrick, KE. Hawkins, JMKM. Delhove, E. Fernandez, C. Soldati, et al. LF. Bullen, A. Nohturfft, SN. Waddington, DL. Medina, JP. Bolaños, TR. McKay. (2018). NF-κB Activity Initiates Human ESC-Derived Neural Progenitor Cell Differentiation by Inducing a Metabolic Maturation Program. Stem Cell Reports. 10,
DC. Miller, SC. Harmer, A. Poliandri, M. Nobles, EC. Edwards, et al. JS. Ware, TV. Sharp, TR. McKay, L. Dunkel, PD. Lambiase, A. Tinker. (2017). Ajmaline blocks INa and IKr without eliciting differences between Brugada syndrome patient and control human pluripotent stem cell-derived cardiac clusters. Stem Cell Research. 25, pp.233-244.
R. Karda, DP. Perocheau, N. Suff, J. Ng, JMKM. Delhove, et al. SMK. Buckley, S. Richards, JR. Counsell, H. Hagberg, MR. Johnson, TR. McKay, SN. Waddington. (2017). Continual conscious bioluminescent imaging in freely moving somatotransgenic mice. Scientific Reports. 7(1),
A. Poliandri, D. Miller, S. Howard, M. Nobles, G. Ruiz-Babot, et al. S. Harmer, A. Tinker, T. McKay, L. Guasti, L. Dunkel. (2017). Generation of kisspeptin-responsive GnRH neurons from human pluripotent stem cells. Molecular and Cellular Endocrinology. 447, pp.12-22.
CA. Vink, JR. Counsell, DP. Perocheau, R. Karda, SMK. Buckley, et al. MH. Brugman, M. Galla, A. Schambach, TR. McKay, SN. Waddington, SJ. Howe. (2017). Eliminating HIV-1 Packaging Sequences from Lentiviral Vector Proviruses Enhances Safety and Expedites Gene Transfer for Gene Therapy. Molecular Therapy. 25(8), pp.1790-1804.
JMKM. Delhove, SMK. Buckley, DP. Perocheau, R. Karda, P. Arbuthnot, et al. NC. Henderson, SN. Waddington, TR. McKay. (2017). Longitudinal in vivo bioimaging of hepatocyte transcription factor activity following cholestatic liver injury in mice. Scientific Reports. 7,
MM. Munye, A. Shoemark, RA. Hirst, JM. Delhove, TV. Sharp, et al. TR. McKay, C. O Callaghan, DL. Baines, SJ. Howe, SL. Hart. (2017). BMI-1 extends proliferative potential of human bronchial epithelial cells while retaining their mucociliary differentiation capacity. American Journal of Physiology - Lung Cellular and Molecular Physiology. 312(2), pp.258-267.
LM. FitzPatrick, TR. McKay (2015). Genome Editing in Stem Cells. Current Stem Cell Reports. 1(1), pp.31-38.
KE. Hawkins, TV. Sharp, TR. McKay (2013). The role of hypoxia in stem cell potency and differentiation. Regen Med. 8(6), pp.771-782.
DG. Rothwell, R. Crossley, JS. Bridgeman, V. Sheard, Y. Zhang, et al. TV. Sharp, RE. Hawkins, DE. Gilham, TR. McKay. (2010). Functional expression of secreted proteins from a bicistronic retroviral cassette based on foot-and-mouth disease virus 2A can be position dependent. Hum Gene Ther. 21(11), pp.1631-1637.
MV. Camarasa, RW. Kerr, SF. Sneddon, N. Bates, L. Shaw, et al. RA. Oldershaw, F. Small, MA. Baxter, TR. Mckay, DR. Brison, SJ. Kimber. (2010). Derivation of Man-1 and Man-2 research grade human embryonic stem cell lines. In Vitro Cell Dev Biol Anim. 46(3-4), pp.386-394.
S. Lunj, R. Duxbury, AM. Russell, Y. Li, SR. Tew, et al. TE. Hardingham, TR. McKay, RE. Hawkins. (2005). Co-expression of SOX 9 and SOX 6 enhances collagen 2 gene expression. European Cells and Materials. 10(SUPPL.2),
R. Duxbury, DE. Gilham, A. Russell, E. Woods, MWJ. Ferguson, et al. TR. McKay, RE. Hawkins. (2005). A gene Therapeutic Approach to scar Reduction at the site of Cutaneous Wounding. European Cells and Materials. 10(SUPPL.2),
IA. McNeish, R. Lopes, SJ. Bell, TR. McKay, M. Fernandez, et al. M. Lockley, SP. Wheatley, NR. Lemoine. (2005). Survivin interacts with Smac/DIABLO in ovarian carcinoma cells but is redundant in Smac-mediated apoptosis. Experimental Cell Research. 302(1), pp.69-82.
IA. McNeish, S. Bell, T. McKay, T. Tenev, M. Marani, et al. NR. Lemoine. (2003). Expression of Smac/DIABLO in ovarian carcinoma cells induces apoptosis via a caspase-9-mediated pathway. Exp Cell Res. 286(2), pp.186-198.
T. McKay, P. Reynolds, S. Jezzard, D. Curiel, C. Coutelle (2002). Secretin-mediated gene delivery, a specific targeting mechanism with potential for treatment of biliary and pancreatic disease in cystic fibrosis. Mol Ther. 5(4), pp.447-454.
RP. Harbottle, RG. Cooper, SL. Hart, A. Ladhoff, T. McKay, et al. AM. Knight, E. Wagner, AD. Miller, C. Coutelle. (1998). An RGD-oligolysine peptide: a prototype construct for integrin-mediated gene delivery. Hum Gene Ther. 9(7), pp.1037-1047.
HL. Gilbert, JL. Buxton, CT. Chan, T. McKay, S. Cottrell, et al. S. Ramsden, RM. Winter, ME. Pembrey, S. Malcolm. (1997). Counselling dilemmas associated with the molecular characterisation of two Angelman syndrome families. J Med Genet. 34(8), pp.651-655.
NA. Bermingham, T. McKay, J. Hoyle, D. Hernandez, JE. Martin, et al. EM. Fisher. (1996). The gene encoding tripeptidyl peptidase II maps to chromosome 1 in the mouse. Mamm Genome. 7(5), pp.390-390.
R. Williams, J. Vesa, I. Järvelä, T. McKay, H. Mitchison, et al. E. Hellsten, A. Thompson, D. Callen, G. Sutherland, D. Luna-Battadano. (1993). Genetic heterogeneity in neuronal ceroid lipofuscinosis (NCL): evidence that the late-infantile subtype (Jansky-Bielschowsky disease; CLN2) is not an allelic form of the juvenile or infantile subtypes. Am J Hum Genet. 53(4), pp.931-935.
HM. Mitchison, AD. Thompson, JC. Mulley, HM. Kozman, RI. Richards, et al. DF. Callen, RL. Stallings, NA. Doggett, J. Attwood, TR. McKay. (1993). Fine genetic mapping of the Batten disease locus (CLN3) by haplotype analysis and demonstration of allelic association with chromosome 16p microsatellite loci. Genomics. 16(2), pp.455-460.
R. Williams, H. Mitchison, T. Mckay, I. Järvelä, RM. Gardiner (1993). Linkage analysis of late-infantile neuronal ceroid-lipofuscinosis (CLN2) using markers on chromosome 16p. J Inherit Metab Dis. 16(2), pp.342-344.
HM. Mitchison, RE. Williams, TR. McKay, DF. Callen, AD. Thompson, et al. JC. Mulley, RL. Stallings, CE. Hildebrand, RK. Moyzis, I. Järvelä. (1993). Refined genetic mapping of juvenile-onset neuronal ceroid-lipofuscinosis on chromosome 16. J Inherit Metab Dis. 16(2), pp.339-341.
JMKM. Delhove, R. Karda, KE. Hawkins, LM. FitzPatrick, SN. Waddington, et al. TR. McKay. (2017). Bioluminescence monitoring of promoter activity in vitro and in vivo. D. Gould. In: Mammalian Synthetic Promoters. Humana Press (Springer Imprint), pp.49-64.