Gene regulation in cancer, in particular epigenetic gene regulation, has been the major focus of Professor Susan Clark's research efforts. Epigenetic means a modification of the DNA and associated chromatin that changes the expression pattern of genes without changing the DNA sequence of the genes. DNA methylation of cytosine residues at CpG dinucleotides is one example of epigenetic gene regulation. Methylation of the promoter sequences of genes is a common process used in the cell to control and modulate the expression of genes. However in cancer the DNA methylation pattern of many genes changes. In fact methylation is a critical component associated with the silencing of many tumour suppressor and related genes in a variety of cancer types.

Education

1982 PhD University of Adelaide
1977 BSc (Hons1) Australian National University

Awards

2009 Australia’s “Top Ten” National Health and Medical Research (NH&MRC) Scientist Award for 2009
2008 Director’s Inaugural Women in Science Lecture Award (Walter and Eliza Hall Institute)
2006 World Technology Award, finalist for Biotechnology
2004 German Science prize (Biochemisch Analytik Award) for outstanding contribution to DNA methylation analysis
2004 The Ruby Payne-Scott Award for contribution of women in science in Australia
2003 Julian Wells Medal for outstanding contribution to gene action and genome structure
2002 RPAH Research Medal for research excellence

Selected Publications

Coolen MW, Stirzaker C, Song JZ, Statham AL, Kassir Z, Moreno CS, Young AN, Varma V, Speed TP, Cowley M, Lacaze P, Kaplan W, Robinson MD and Clark SJ (2010). Consolidation of the cancer genome into domains of repressive chromatin by long range epigenetic silencing (LRES) reduces transcriptional plasticity. Nat Cell Biol 12: 235-246.

Hinshelwood RA, Melki JR, Huschtscha LI, Paul C, Song JZ, Stirzaker C, Reddel RR and Clark SJ (2009). Aberrant de novo methylation of the p16INK4A CpG island is initiated post gene silencing in association with chromatin remodelling and mimics nucleosome positioning. Hum Mol Genet 18: 3098-3109.

Coolen MW, Statham AL, Gardiner-Garden M and Clark SJ (2007). Genomic profiling of CpG methylation and allelic specificity using quantitative high-throughput mass spectrometry: critical evaluation and improvements. Nucleic Acids Res 35: e119.

Hinshelwood RA, Huschtscha LI, Melki J, Stirzaker C, Adipranoto A, Vissel B, Ravasi T, Wells C, Hume DA, Reddel RR and Clark SJ (2007). Concordant epigenetic silencing of transforming growth factor signaling pathway genes occurs early in breast carcinogenesis. Cancer Res 67: 11517-11527.

Clark SJ (2007). Action at a distance: Epigenetic silencing of large chromosomal regions in carcinogenesis. Hum Mol Genet 16: R88-R95.

Clark SJ, Statham A, Stirzaker C, Molloy PL and Frommer M. DNA methylation: bisulphite modification and analysis. Nature Protocols 2007; 1: 2353-2364.

Frigola J, Song J, Stirzaker C, Hinshelwood RA, Peinado MA, Clark SJ. Epigenetic remodeling in colorectal cancer results in coordinate gene supression across an entire chromosome band. Nat Genet 2006; 38(5):540-549.

Stirzaker JZ, Song BD, Davidson B, Clark SJ. Transcriptional gene silencing promotes DNA hypermethylation through a sequential change in chromatin modification in cancer cells. Cancer Research 2004; 64:3871-3877.

Song J, Stirzaker C, Harrison J, Melki J, Clark, S. Hypermethylation trigger of the glutathione-S-transferase gene (GSTP1) in prostate cancer cells. Oncogene 2002; 21: 1048-1061.

Millar D, Molloy P,  Clark S. A distinct sequence (ATAAA)n separates methylated and unmethylated domains at the 5' end of the GSTP1 CpG island. J Biol Chem 2000; 275: 24893-24899.

Melki J, Vincent PC, Clark SJ. Concurrent DNA Hypermethylation of Multiple Genes in Acute Myeloid Leukaemia. Cancer Res 1999; 59: 3730-3740.

Warnecke PM, Biniszkiewicz D, Jaenisch R, Frommer M, Clark SJ. Sequence-specific methylation of the mouse H19 gene in embyronic cells deficient in the Dmnt-1 gene. Dev Genetics 1998; 22: 111-121.

Stirzaker C, Millar DS, Paul CL, Warnecke PM, Harrison J, Vincent PC, Frommer M, Clark SJ. Extensive DNA Methylation Spanning the Rb promoter in Retinoblastoma Tumours. Cancer Res 1997; 57: 2229-2237.

Clark SJ, Harrison J, Frommer MF. CpNpG methylation: de novo and maintenance activities in mammalian cells. Nature Genetics 1995; 10: 20-27.

Clark SJ, Harrison J, Paul CL, Frommer MF. High sensitivity mapping of methylated cytosines. Nucleic Acids Res 1994; 22: 2990-2997.

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