DNA replication and breast cancer
Based at Department of Pathology, Tennis Court Road
Supervised by Prof Christine Watson
Cell proliferation is tightly regulated in normal cells but is frequently dysregulated in cancer. We have identified a novel gene, Roma, that controls progression through the cell cycle. When Roma is deleted from mammary cells, they accumulate DNA damage which results in chromosomal abnormalities and an abnormal hyperplastic phenotype which may predispose to cancer. The aim of this project is to investigate the mechanism by which Roma controls cell proliferation and how it interacts with other genes such as Gata3 to promote breast tumourigenesis and metastasis.
Khaled WT, Choon Lee S, Stingl J, Chen X, Raza Ali H, Rueda OM, Hadi F, Wang J, Yu Y, Chin SF, Stratton M, Futreal A, Jenkins NA, Aparicio S, Copeland NG, Watson CJ, Caldas C, Liu P. (2015) BCL11A is a triple-negative breast cancer gene with critical functions in stem and progenitor cells. Nature Commun. Jan 9;6:5987
Sargeant, TJ, Lloyd-Lewis B, Resemann,HK, Skepper J, Watson CJ (2014) Stat3 regulates lysosomal membrane permeabilisation by uptake of milk fat globules to control cell death during mammary gland involution. Nature Cell Biology, Nov;16(11):1057-68.
Associated News & Views article: Nature Cell Biology. 2014 Oct.31;16(11):1029-31.
Campbell JJ, Hume RD, Watson CJ. (2014) Engineering mammary gland in vitro models for cancer diagnostics and therapy. Mol Pharm. Jul 7;11(7):1971-81.
Oliver CH, Khaled WT, Frend H, Nichols J, Watson CJ.(2012) The Stat6-regulated KRAB domain zinc finger protein Zfp157 regulates the balance of lineages in mammary glands and compensates for loss of Gata-3. Genes & Dev. May 15;26(10):1086-97.
More information on the supervisor’s research can be found on their research group website