| Professor Stephen Jane |
|
Director BMRL
Stephen M. Jane MBBS, PhD, FRACP, FRCPA
Principal Research Fellow
Director
Bone Marrow Research Laboratories
Professor Jane completed a medical degree at Monash University, Australia in 1981 and specialised in Hematology, completing his clinical training in 1990. He also completed a PhD from Monash University in 1990, and was then a Cooleys Anemia Foundation Fellow at the NIH in Bethesda, MD until 1993. He was a faculty member at St Jude Childrens Research Hospital until 1995, then moved to the Bone Marrow Research Laboratories (BMRL) in Melbourne, Australia as a Wellcome Senior Research Fellow. He is currently Director of the BMRL, and a Principal Research Fellow of the National Health and Medical Research Council.
Research Interests
- Transcriptional control of epidermal morphogenesis and skin development during vertebrate embryogenesis
- Transcriptional control of erythropoiesis during human development
Professor Jane's research program at the BMRL focuses on transcriptional regulation during embryogenesis, with an emphasis on erythropoiesis and globin gene regulation, and more recently, skin development. The group has studied the regulation of human fetal (g) globin gene expression for many years, trying to define the transcription factors involved in activation and silencing of the genes. As a result of this, the group cloned NF-E4, a gene involved in the preferential expression of the g-genes. Recently, we have identified the arginine methyltransferase PRMT5 as a critical molecule in fetal globin gene silencing.
We have also identified a number of novel genes/alleles involved in red blood cell production using an ENU mutagenesis screen in mice. The mechanistic roles of these genes are currently being elucidated.
Our interest in skin development arose through the identification of a family of transcription factors related to Drosophila grainyhead. We have cloned three novel mammalian homologues of this family and have shown that they each play critical roles in different aspects of development. The most extensively studied member, Grhl3, is critical for a wide range of epidermal morphogenetic events including neural tube closure, wound healing and skin barrier formation. The mechanisms underlying these roles, and the roles of the other Grhl factors are the subject of our ongoing research in this area.
Publications
Siggins, S.L., Nguyen, N-Y.N., McCormack, M.P., Vasudevan, S., Villani, R., Jane, S.M., Wainwright, B.J., and Curtis, D.J. The hedgehog Receptor Patched1 regulates myeloid and lymphoid progenitors by distinct cell-extrinsic mechanisms. Blood 11:995-1004, 2009.
Rank, G., Sutton, R., Marshall, V., Lundie, R., Caddy, J., Romeo, T., Fernandez, K., McCormack, M., Cooke, B.M., Foote, S.J., Crabb, B.S., Curtis, D.J., Hilton, D.J., Kile, B.T., and Jane, S.M. Novel roles for erythroid Ankyrin-1 revealed through an ENU-induced null mouse mutant. Blood 113:3352-3362, 2009.
Zhao, Q., Rank, G., Tan, Y.T., Li, H., Moritz, R.L., Simpson, R.J., Cerruti, L., Curtis, D.J., Patel, D.J., Allis, C.D., Cunningham, J.M., and Jane, S.M. PRMT5-mediated methylation of histone H4R3 recruits DNMT3A coupling histone and DNA methylation in gene silencing. Nature Structural Molecular Biology 16:304-311, 2009.
Hislop, N.R., Caddy, J., Ting, S.B., Auden, A., Vasudevan, S., King, S.L., Lindeman, G.J., Visvader, J.E., Cunningham, J.M., and Jane, S.M.. Grhl3 and Lmo4 play coordinate roles in epidermal migration. Developmental Biology, 321:263-72, 2008.
Wilanowski, T., Caddy, J., Ting, S.B., Hislop, N.R., Cerruti, L., Auden, A., Zhao, L.L., Asquith, S., Ellis, S., Sinclair, R., Cunningham, J.M., and Jane, S.M. Perturbed desmosomal cadherin expression in grainy head-like 1-null mice. EMBO Journal 27: 886-897, 2008.
Salmon, J.M., Slater, N.J., Hall, M.A., McCormack, M.P., Nutt, S.L., Jane, S.M., and Curtis DJ. Aberrant mast cell differentiation in mice lacking the stem cell leukemia gene. Blood, 110: 3573-3581, 2007.
Dow, L.E., Kauffman, J.S., Caddy, J., Peterson, A.S., Jane, S.M., Russell, S.M., and Humbert, P.O. The tumour suppressor Scribble dictates cell polarity during directed epithelial migration: regulation of Rho GTPase recruitment to the leading edge. Oncogene, 26:2272-2282, 2007.
McCormack, M.P., Hall, M.A., Schoenwaelder, S.M., Zhao, Q., Ellis, S., Prentice, J.A., Clarke, A.J., Slater, N.J., Salmon, J.M., Jackson, S.P., Jane, S.M., and Curtis, D.J. A critical role for the transcription factor Scl in platelet production during stress thrombopoiesis. Blood, 108: 2248-2256, 2006.
Auden, A., Caddy, J., Wilanowski, T., Ting, S.B., Cunningham, J.M., and Jane, S.M. Spatial and temporal expression of the Grainy head-like transcription factor family during murine development. Mechanisms of Development – Gene Expression Patterns, 6:964-970, 2006.
Bosè, F., Fugazza, C., Casalgrandi, M., Capelli, A., Cunningham, J.M., Zhao, Q., Jane, S.M., Ottolenghi, S., and Ronchi, A. Functional interaction of CP2 with GATA-1 in the regulation of erythroid promoters. Molecular and Cellular Biology, 26: 3942-3954, 2006.
Zhao, Q., Zhou, W-L., Rank, G., Sutton, R., Wang, X., Cumming, H., Cerruti, L., Cunningham, J.M., and Jane, S.M. Repression of human g-globin gene expression by a short isoform of the NF-E4 protein is associated with loss of NF-E2 and RNA polymerase II recruitment to the promoter. Blood, 107: 2138-2145, 2006.
Ting, S.B., Caddy, J., Wilanowski, T., Auden, A., Cunningham, J.M., Elias, P.M., Holleran, W.M., Jane, S.M. The epidermis of Grhl3-null mice displays altered lipid processing and cellular hyperproliferation. Organogenesis, 2:33-35, 2005.
Teng, M.W.L., Kershaw, M.H., Hayakawa, Y., Cerutti, L., Jane, S.M., Darcy, P.K., and Smyth, M.J. T cells gene-engineered with DAP12 mediate effector function in an NKG2D-dependent and MHC-independent manner. Journal of Biological Chemistry, 280: 38235-28241, 2005.
McCormack, M., Hall, M., Jane, S.M., Curtis, D.J. Functional but abnormal adult erythropoiesis in the absence of the stem cell leukemia gene. Molecular and Cellular Biology, 25:6355-6362, 2005.
Moeller, M., Haynes, N.M., Kershaw, M.H., Jackson, J.T., Teng, M.W.L., Street, S.E., Cerutti, L., Jane, S.M., Trapani, J.A., Smyth, M.J. and Darcy, P.K. Adoptive transfer of gene-engineered CD4+ helper T cells induces potent primary and secondary tumor rejection. Blood, 106: 2995-3001, 2005.
Ting, S.B., Caddy, J., Hislop, N., Wilanowski, T., Auden, A., Zhao, L-L., Ellis, S., Kaur, P., Uchida, Y., Elias, P.M., Holleran, W.M., Cunningham, J.M., and Jane, S.M. A homolog of Drosophila grainy head is essential for epidermal integrity in mice. Science, 308:411-413, 2005.
Tao, J., Kuliyev, E., Wang, X., Li, X., Wilanowski, T., Jane, S.M., Mead, P.E., and Cunningham J.M. BMP4-dependent expression of Xenopus Grainyhead-like 1 is essential for epidermal differentiation. Development, 132:1021-1034, 2005.
Voskoboinik, I., Gouel, M-C., Debono, A., Browne, K., Cretney, E., Darcy, P.K., Jane, S.M., Smyth, M.J., and Trapani, J.A. The functional basis for hemophagocytic lymphohistiocytosis (HLH) in a patient with co-inherited missense mutations in perforin. Journal of Experimental Medicine, 200:811-816, 2004.
Zhao, Q., Cumming, H., Cerruti, L., Cunningham, J.M., and Jane, S.M. Site-specific acetylation of the fetal globin activator NF-E4 prevents its ubiquitination and regulates its interaction with the histone deacetylase, HDAC1. Journal of Biological Chemistry, 279:41477-41486, 2004.
Parekh, V., McEwan, A., Barbour, V., Takahashi, Y., Rehg, J.E., Jane, S.M., and Cunningham, J.M. Defective extra-embryonic angiogenesis in mice lacking LBP-1a, a member of the grainyhead family of transcription factors. Molecular and Cellular Biology, 24: 7113-7129, 2004.
Zhou, W-L., Zhao, Q., Sutton, R., Cumming, H., Wang, X., Cerruti, L., Hall, M., Wu, R., Cunningham, J.M., and Jane, S.M. The role of NF-E4 in human globin gene switching, Journal of Biological Chemistry, 279: 26227-26232, 2004.
Gothert, J.R., Gustin, S.E., van Eekelen, J.A., Schmidt, U., Hall, M., Jane, S.M., Green, A.R., Gottgens, B., Izon, D.J., and Begley C.G. Genetically tagging endothelial cells in vivo: bone marrow-derived cells do not contribute to tumor endothelium, Blood, 104:1769-1777, 2004.
Tainton, K.M., Smyth, M.J., Jackson, J.T., Tanner, J.E., Cerruti, L., Jane, S.M., Darcy, P.K. and Johnstone, R.W. Mutational analysis of P-glycoprotein: suppression of caspase activation in the absence of ATP-dependent drug efflux. Cell Death and Differentiation, 11: 1028-1037, 2004.
Moeller, M., Haynes, N.M., Trapani, J.A., Teng, M.W.L., Jackson, J.T., Tanner, J.E., Cerutti, L., Jane, S.M., Kershaw, M.H., Smyth, M.J. and Darcy, P.K. A functional role for CD28 co-stimulation in tumor recognition by single-chain receptor-modified T cells. Cancer Gene Therapy, 11:371-379, 2004.
Curtis, D.J., Hall, M.A., van Stecklenberg, L.J., Robb, L., Jane, S.M., and Begley, C.G. SCL is required for normal function of hematopoietic multi-potent progenitors. Blood, 103: 3342-3348, 2004.
Ting, S.B., Wilanowski, T., Auden A., Hall, M., Voss, A.K., Thomas, T., Parekh, V., Cunningham, J.M., and Jane, S.M. Inositol and folate resistant neural tube defects in mice lacking the epithelial-specific factor Grhl3. Nature Medicine 9: 1513-1519, 2003.
Ting, S.B., Wilanowski, T. Cerruti, L., Zhao, L., Cunningham, J.M., and Jane, S.M. The identification and characterisation of human Sister-of-MGR (SOM) expands the grainyhead-like family of developmental transcription factors. Biochemical Journal, 370: 953-962, 2003.
Brown, R.C., Pattison, S., van Ree, J., Coghill, E., Perkins, A., Jane, S.M. and Cunningham, J.M. Distinct domains of Erythroid Kruppel-Like Factor modulate chromatin remodeling and transactivation at the endogenous beta-globin gene promoter.Molecular and Cellular Biology 22(1):161-170, 2002.
Tuckfield, A.M., Clouston, D.R., Wilanowski, T.M., Zhao, L.L., Cunningham, J.M. and Jane, S.M. Binding of the RING polycomb proteins to specific target genes in complex with the grainyhead-like family of developmental transcription factors. Molecular and Cellular Biology, 22: 1936-1946, 2002.
Wilanowski, T.M., Tuckfield, A.M., Cerruti, L., O Connell, S., Saint, R., Tao, J., Cunningham, J.M. and Jane, S.M. A highly conserved novel family of mammalian developmental transcription factors related to Drosophila grainyhead. Mechanisms of Development, 114: 37-50, 2002.
Holmes, M.H., Haley, J.D., Cerutti, L., Zhou, W-L., Zogos, H., Smith, D.E., Cunningham, J.M. and Jane, S.M. Identification of Id2 as a globin regulatory protein by representational difference analysis of K562 cells induced to express g-globin with a fungal compound. Molecular and Cellular Biology 19: 4182-4190, 1999.
Ramamurthy, L., Barbour, V., Tuckfield, A., Clouston, D.R., Topham, D., Cunningham, J.M. and Jane, S.M. The murine transcription factor, NF2d9 compensates for loss of CP2 expression in mice with a targeted deletion of the CP2 gene. Journal of Biological Chemistry 276: 7836-7842, 2001.
Zhou, W-L., Clouston, D.R., Wang, X. Cerruti, L., Cunningham, J.M. and Jane, S.M. Identification and characterisation of human NF-E4, the tissue-restricted component of the stage selector protein complex. Molecular and Cellular Biology, 20: 7662-7672, 2000. |
