Blood development - Andrew Perkins

A/Prof Andrew Perkins

1. Transcriptional hierarchies which are active during embryonic stem (ES) cell differentiation into mesoderm-derived tissues such as the kidney and blood. The methodologies used include: directed differentiation of ES cells in various recombinant growth factors, gene targeting and BAC recombineering for generating reporter ES cell lines and mice in which stem cells can be followed by epifluorescence and FACS, expression profiling and chromatin immuno-precipitation.

2. Transcriptional regulation of erythropoiesis. Mutations in the globin genes are the most common genetic mutations worldwide. These mutations are responsible for thalassaemia and sickle cell disease, which cause serious morbidity and mortality. We are interested in trying to decipher the complex process of haemoglobin switching at a molecular level. The long-term goal is to design new drugs that target key regulators of this process and thereby reactivate foetal haemoglobin in adults.

3. Zebrafish are used as a vertebrate model for dissection of some of the earliest transcriptional events which underpin morphogenetic movements which lead to the generation and ‘education’ of stem cells within the mesoderm germ layer. Once again we are concerned primarily with the activities of key ‘master regulator’ transcription factors of zinc finger and homeodomain classes. We have established expression profiling in zebrafish and have established assays and systems for study of morphogenesis.

4. The role of played by the Kruppel-like factor (KLF) family of zinc finger genes in normal differentiation and human skin, colon and blood cancers.


Research projects

• Studying transcriptional hierarchies active during ES cell differentiation into mesoderm-derived tissues


• Investigating the transcriptional regulation of erythropoiesis


• Studying morphogenesis using zebrafish models


• Researching role of KLF in differentiation and cancer

Key Publications

Cloonan, N., Forrest, A.R., Kolle, G., Gardiner, B.B., Faulkner, G.J., Brown, M.K., Taylor, D.F., Steptoe, A.L., Wani, S., Bethel, G., Robertson, A.J., Perkins, A.C., Bruce, S.J., Lee, C.C., Ranade, S.S., Peckham, H.E., Manning, J.M., McKernan, K.J., and Grimmond, S.M. (2008). Stem cell transcriptome profiling via massive scale shotgun short tag sequencing. Nature Methods 5: 613-619.

Dinger, M.E., Amaral, P.P., Mercer, T.R., Pang, K.C., Bruce, S.J., Gardiner, B.B., Askarian-Amiri, M.E., Ru, K., Solda, G., Simons, C., Sunkin, S.M., Crowe, M.L., Grimmond, S.M., Perkins, A.C., and Mattick, J.S. (2008). Non-coding RNA in Mouse ES cell pluripotency and differentiation. Genome Research 18: 1433-1445.

Whitington, T., Perkins, A.C., and Bailey, T.L. (2008). Using epigenetic chromatin information to improve in vivo transcription factor binding predictions. Nucleic Acids Research Nov 6 [Epub]

Bruce, S.J., Gardiner, B.B., Burke, L.J., Gongora, M.M., Grimmond, S.M., and Perkins, A.C. (2007). Dynamic transcription programs during ES cell differentiation towards mesoderm in serum versus serum-free (BMP4) culture. BMC Genomics 8: 365.

Wilkins, S.J., Yoong, S., Verkade, H., Mizoguchi, T., Plowman, S.J., Hancock, J.F., Kikuchi, Y., Heath, J.K., and Perkins, A.C. (2007). Mtx2 directs zebrafish morphogenetic movements during epiboly by regulating microfilament formation. Developmental Biology 314: 12-22.

Hodge, D., Coghill, E., Keys, J., Maguire, T., Hartmann, B., McDowall, A., Weiss, M., Grimmond, S., and Perkins, A.C. (2006). A global role for EKLF in definitive and primitive haematopoiesis. Blood 107: 3357-3370.

Papathanasiou, P., Perkins, A.C., Cobb, B.S., Ferrini, R., Sridharan, R., Hoyne, G.F., Nelms, K.A., Smale, S.T., and Goodnow, C.C. (2003). Widespread failure of hematolymphoid differentiation caused by a recessive niche-filling allele of the Ikaros transcription factor. Immunity 19: 131-144.

Perkins, A.C., Sharp, A.H., and Orkin, S.H. (1995). Lethal β-thalassemia in mice lacking the erythroid CACCC-transcription factor EKLF. Nature 375: 318-322.

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