Aim To understand the regulation of gene expression during pre-implantation development and to use this and other knowledge to develop methods for directing cell fate; to collaborate with others in the use of these procedures to develop cells for research and therapy.
Approach We collaborate internationally to establish methods of using stem cells to identify new drugs and treatments for degenerative disorders including cardiovascular diseases and Motor Neuron Disease. These diseases involve the loss of normal function in specific cell types and are often fatal. We are developing accurate and reproducible techniques to change cells directly from one cell type to another, including skin to nerve or heart cell lineages which are directly affected in our diseases of interest. These innovative techniques to control cell fate also depend upon ongoing research to understand the key molecular mechanisms that regulate early embryo development and tissue formation.
Bilican B, Serio A, Barmada SJ, Nishimura AL, Sullivan GJ, Carrasco M, Phatnani HP, Puddifoot CA, Story D, Fletcher J, Park IH, Friedman BA, Daley GQ, Wyllie DJ, Hardingham GE, Wilmut I, Finkbeiner S, Maniatis T, Shaw CE, Chandran S. 2012. Mutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerability. PNAS 109(15):5803-8.
Zhou W, Hannoun Z, Jaffray E, Medine CN, Black JR, Greenhough S, Zhu L, Ross JA, Forbes S, Wilmut I, Iredale JP, Hay RT, Hay DC. 2012. SUMOylation of HNF4α Regulates Protein Stability and Hepatocyte Function. J Cell Sci. 2012 Apr 14. [Epub ahead of print].
Wongtawan, T., Taylor, J. E., Lawson, K. A., Wilmut, I., & Pennings, S. 2011. Histone H4K20me3 and HP1α are late heterochromatin markers in development, but present in undifferentiated embryonic stem cells. Journal of Cell Science 124(Pt 11):1878-90.
Taylor, J., Wilmut, I., & Sullivan, G. 2010. What are the limits to cell plasticity?. Stem Cell Research 20(5):502-3.
Wang, S., Kou, Z., Jing, Z., Zhang, Y., Guo, X., Dong, M., Wilmut, I., & Gao, S. 2010. Proteome of mouse oocytes at different developmental stages. PNAS 107(41):17639-44.
Sullivan GJ, Hay DC, Park I, Fletcher J, Hannoun Z, Payne CM, Dalgetty D, Black JR, Ross JA, Samuel K, Wang G, Daley GQ, Lee J, Church GM, Forbes SJ, Iredale JP & Wilmut I. 2010. Generation of Functional Human Hepatic Endoderm from Human Induced Pluripotent Stem Cells. Hepatology 51(1):329-335. Press Release.