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.
The lab 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.
Lab Website: Holland Lab
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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., Tutt, A.N.J., Lord, C.J., Chapman, J.R.*, Holland, A.J.*. Nature. In Press. (2020)
WBP11 is required for splicing the TUBGCP6 pre-mRNA to promote centriole duplication. Park, E., Scott, P.M., Clutario, K.M., Cassidy, K.B., Zhan, K., Gerber and Holland, A.J. Journal of Cell Biology 219(1). (2019).
Massive centriole production can occur in the absence of deuterosomes in multiciliated cells. Mercey, O.*, Levine, M.S.*, LoMastro, G., Rostaing, P., Brotslaw, E., Gomez, V., Kumar, A., Spassky, N., Mitchell, B.J., Meunier, A.* and Holland, A.J.* Nature Cell Biology 21: 1544-52. (2019).
PLK4 promotes centriole duplication by phosphorylating STIL to link the procentriole to the microtubule wall. Moyer, T.C. and Holland, A.J. eLIFE 8: e46054. (2019).
Once and only once: mechanisms of centriole duplication and their deregulation in disease. Nigg, E.A., Holland, A.J. Nature Reviews Molecular Cell Biology 19(5): 297-312. (2018).
Centrosome amplification is sufficient to promote spontaneous tumorigenesis in mammals. Levine, M.S., Bakker, B., Boeckx, B., Moyett, J., Lu, J., Vitre, B., Spierings, D.C., Lansdorp, P.M., Cleveland, D.W., Lambrechts, D., Foijer, F. and Holland, A.J. Developmental Cell 40(3): 313-22. (2017).
A USP28-53BP1-p53-p21 signaling axis arrests growth following centrosome loss or prolonged mitosis. Lambrus, B.G., Daggubati, V., Uetake, Y., Scott, P.M., Clutario, K.M., Sluder, G., Holland, A.J. Journal of Cell Biology 214:143-153. (2016).