Cell division is a fundamental process forming the basis for life itself. Each time a cell divides, it makes a complete copy of its entire genome and segregates this genome such that both daughter cells receive all the genetic information required for further growth and development. Errors in the distribution of chromosomes during mitosis lead to the production of cells with an abnormal chromosome content, which in early development lead to lethal growth defects and may later contribute to the development of cancer.

 

The Holland lab is interested in the molecular mechanisms that control accurate chromosome distribution and the role that mitotic errors play in human health and disease. Our work utilizes a combination of chemical biology, biochemistry, cell biology and genetically engineered mice to study pathways involved in mitosis and their effect on cell and organism physiology. A major focus of the group is to develop cell and animal-based models to study the role of cell division defects in genome instability and tumorigenesis. 

 

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Keeping tack of time: The fundamentals of cellular clocks Gliech, C.R and Holland, A.J.* Journal of Cell Biology 291(11). (2020). [ link ]
Targeting TRIM37-driven centrosome dysfunction in 17q23-amplified breast cancer. Yeow, Z.Y.*, Lambrus, B.G.*, Marlow, R., Zhan, K.H., Durin, M., Evans, L.T., Scott, P.M., Phan, T., Park, E., Ruiz, L.A., Moralli, D., Knight, E.G., Badder, L.M., Novo, D., Haider, S., Green, C.M., Turr, A.N.J., Lord, C.J., Chapman, J.R.* and Holland, A.J.* Nature 585(7824). (2020). [ link ]
Cell fitness screens reveal a conflict between LINE-1 retrotransposition and DNA replication. Ardeljan, D., Steranka, J.P., Liu, C., Liz, C., Taylor, M.S., Payer, L.M., Gorbounov, M., Sarnecki, J.S., Deshpande, V., Hruban, R.H., Boeke, J.D., Fenyo, D., Wu, P.H., Smogorzewska, A., Holland, A. and Burns, K.H. Nature Structure and Molecular Biology 27(2): 168-178. (2020). [ link ] [ pdf ]