Colin Stewart has been a pioneer in developing many of the techniques now widely used in mouse experimental genetics, in establishing protocols for deriving embryonic stem (ES) lines, uniparental ES lines, and for the derivation of the first human ES lines. He was instrumental in identifying the cytokine LIF as being crucial to sustaining stem cell pluripotency (Nature 1988 v336: p684). Subsequently he showed that LIF and its signalling pathway is critical to regulating uterine receptivity for embryo implantation in mammals (Nature 1992 v359: p76). He developed numerous mouse models of human congenital diseases, particularly those arising from defective genomic imprinting such as Prader-Willi.
Over the last decade his interests have centered on the laminopathies, a heterogeneous collection of diseases all arising from mutations in the LaminA gene that cause cardiovascular disease, muscular dystrophy, lipodystrophy (reduced fat formation) and the premature ageing disease Hutchinson Gilford Progeria (HGPS). He collaborated with Nicolas Lévy, in being the first to show that mutations in the LMNA gene cause Progeria (Science 2003 v336: p684), and has also made mouse models of many of the laminopathies, including progeria. He developed the first iPSCs lines derived from patient fibroblasts in establishing an in vitro model for HGPS. Currently, he is a founding partner of Neuvocor Therapeutics that is developing new treatments to ameliorate cardiomyopathies and vascular disease.
Selected publications (from 230 publications H-index 101)
Solovei, I., et al (2013) LBR and lamin A/C sequentially tether peripheral heterochromatin and inversely regulate differentiation Cell 152(3) 584-98
Horn H.F., et al. (2013) A mammalian KASH domain protein coupling meiotic chromosomes to the cytoskeleton. J Cell Biol. 202 (7): 1023-39
Ramanathan N, Lim N, and Stewart CL. (2015) DDX5/p68 RNA helicase expression is essential for initiating adipogenesis. Lipids Health Dis. 14(1): 160.
Chojnowski, A. et al (2018) 2C-BioID: An advanced two component BioID system for precision mapping of protein interactomes. iScience Dec 21;10:40-52
Chojnowski A, et al .(2019) Protein-Protein Interaction Mapping by 2C-BioID. Curr Protoc Cell Biol. Sep;84(1)
Loo, T-H, et al (2019) The mammalian LINC complex component SUN1 regulates muscle regeneration by modulating Drosha activity. eLIFE Nov 5;8. pii: e49485. 228:
Chojnowski A, et al (2020) Heterochromatin loss as a determinant of progerin-induced DNA damage in Hutchinson-Gilford Progeria. Aging Cell. Mar;19(3):e13108.
Chai. R.J., et al (2020) Disrupting the LINC complex by AAV mediated gene transduction prevents dilated cardiomyopathy progression. Nat Comm (under revision)