Kristie Dickson is a cell and molecular biologist working in the Translational Oncology Group at UTS in the School of Life Sciences (SoLS), Faculty of Science.
She was awarded a Bachelor Science (Honours) in Biological/Biomedical Sciences from UTS in 1998. After completing her studies Kristie worked as a Research Assistant at the Department of Physiology at the University of Sydney investigating the regulation of ion transport in kidney epithelium using yeast-2-hybrid models. In 2000 she moved to the Kolling Institute of Medical Research at Royal North Shore Hospital to study the effects of Insulin-Like Binding Proteins (IGFBPs) on models of breast cancer. In 2003 she left academic research to work as a research scientist for the then start-up Biotechnology Company EnGeneIC Pty Ltd. Here she worked on a novel drug delivery system that targets cancer cells and her contributions led to a seminal paper published in Cancer Cell in 2007.
In 2007 she joined Professor Deborah Marsh’s laboratory at the Kolling Institute of Medical Research, to work on malignancies that affect women, with a focus on ovarian cancer, investigating chemoresistance, new therapies and epigenomic regulation. She moved to UTS with Professor Marsh in 2018 to continue this research.
- Australia New Zealand Gynaecological Oncology Group (ANZGOG, 2015 -)
Kristie Dickson’s major research interests include:
- Genetics of cancer
- Epigenetics / epigenomics, including histone modifications and malignancy
- Ovarian cancer
- Women’s cancers including ovarian, endometrial and breast cancer
- Cancer associated signaling pathways
Cole, AJ, Dickson, K-A, Liddle, C, Stirzaker, C, Shah, JS, Clifton-Bligh, R & Marsh, DJ 2020, 'Ubiquitin chromatin remodelling after DNA damage is associated with the expression of key cancer genes and pathways', CELLULAR AND MOLECULAR LIFE SCIENCES.View/Download from: Publisher's site
There is growing evidence highlighting the importance of monoubiquitination as part of the histone code. Monoubiquitination, the covalent attachment of a single ubiquitin molecule at specific lysines of histone tails, has been associated with transcriptional elongation and the DNA damage response. Sites function as scaffolds or docking platforms for proteins involved in transcription or DNA repair; however, not all sites are equal, with some sites resulting in actively transcribed chromatin and others associated with gene silencing. All events are written by E3 ubiquitin ligases, predominantly of the RING (really interesting new gene) finger type. One of the most well-studied events is monoubiquitination of histone H2B at lysine 120 (H2Bub1), written predominantly by the RING finger complex RNF20-RNF40 and generally associated with active transcription. Monoubiquitination of histone H2A at lysine 119 (H2AK119ub1) is also well-studied, its E3 ubiquitin ligase constituting part of thePolycomb Repressor Complex 1 (PRC1), RING1B-BMI1, associated with transcriptional silencing. Both modifications are activated as part of the DNA damage response. Histone monoubiquitination is a key epigenomic event shaping the chromatin landscape of malignancy and influencing how cells respond to DNA damage. This review discusses a number of these sites and the E3 RING finger ubiquitin ligases that write them.
Cole, AJ, Zhu, Y, Dwight, T, Yu, B, Dickson, K-A, Gard, GB, Maidens, J, Valmadre, S, Gill, AJ, Clifton-Bligh, R & Marsh, DJ 2017, 'Comprehensive analyses of somatic TP53 mutation in tumors with variable mutant allele frequency', Scientific data, vol. 4, pp. 170120-170120.View/Download from: Publisher's site
Somatic mutation of the tumor suppressor gene TP53 is reported in at least 50% of human malignancies. Most high-grade serous ovarian cancers (HGSC) have a mutant TP53 allele. Accurate detection of these mutants in heterogeneous tumor tissue is paramount as therapies emerge to target mutant p53. We used a Fluidigm Access Array™ System with Massively Parallel Sequencing (MPS) to analyze DNA extracted from 76 serous ovarian tumors. This dataset has been made available to researchers through the European Genome-phenome Archive (EGA; EGAS00001002200). Herein, we present analyses of this dataset using HaplotypeCaller and MuTect2 through the Broad Institute's Genome Analysis Toolkit (GATK). We anticipate that this TP53 mutation dataset will be useful to researchers developing and testing new software to accurately determine high and low frequency variant alleles in heterogeneous aneuploid tumor tissue. Furthermore, the analysis pipeline we present provides a valuable framework for determining somatic variants more broadly in tumor tissue.
Cole, AJ, Dwight, T, Gill, AJ, Dickson, K-A, Zhu, Y, Clarkson, A, Gard, GB, Maidens, J, Valmadre, S, Clifton-Bligh, R & Marsh, DJ 2016, 'Assessing mutant p53 in primary high-grade serous ovarian cancer using immunohistochemistry and massively parallel sequencing', SCIENTIFIC REPORTS, vol. 6.View/Download from: Publisher's site
Dickson, KA, Cole, AJ, Gill, AJ, Clarkson, A, Gard, GB, Chou, A, Kennedy, CJ, Henderson, BR, Fereday, S, Traficante, N, Alsop, K, Bowtell, DD, de Fazio, A, Clifton-Bligh, R & Marsh, DJ 2016, 'The RING finger domain E3 ubiquitin ligases BRCA1 and the RNF20/RNF40 complex in global loss of the chromatin mark histone H2B monoubiquitination (H2Bub1) in cell line models and primary high-grade serous ovarian cancer', Human Molecular Genetics, vol. 25, no. 24, pp. 5460-5471.View/Download from: Publisher's site
© The Author 2016. Enzymatic factors driving cancer-associated chromatin remodelling are of increasing interest as the role of the cancer epigenome in gene expression and DNA repair processes becomes elucidated. Monoubiquitination of histone H2B at lysine 120 (H2Bub1) is a central histone modification that functions in histone cross-talk, transcriptional elongation, DNA repair, maintaining centromeric chromatin and replication-dependent histone mRNA 3'-end processing, as well as being required for the differentiation of stem cells. The loss of global H2Bub1 is seen in a number of aggressive malignancies and has been linked to tumour progression and/or a poorer prognosis in some cancers. Here, we analyse a large cohort of high-grade serous ovarian cancers (HGSOC) and show loss of global H2Bub1 in 77% (313 of 407) of tumours. Loss of H2Bub1 was seen at all stages (I-IV) of HGSOC, indicating it is a relatively early epigenomic event in this aggressive malignancy. Manipulation of key H2Bub1 E3 ubiquitin ligases, RNF20, RNF40 and BRCA1, in ovarian cancer cell line models modulated H2Bub1 levels, indicative of the role of these RING finger ligases in monoubiquitination of H2Bub1 in vitro. However, in primary HGSOC, loss of RNF20 protein expression was identified in just 6% of tumours (26 of 424) and did not correlate with global H2Bub1 loss. Similarly, germline mutation of BRCA1 did not show a correlation with the global H2Bub1 loss. We conclude that the regulation of tumourassociated H2Bub1 levels is complex. Aberrant expression of alternative histone-associated 'writer' or 'eraser' enzymes are likely responsible for the global loss of H2Bub1 seen in HGSOC.
Dickson, K-A, Cole, AJ, Gill, AJ, Clarkson, A, Gard, GB, Chou, A, Kennedy, CJ, Henderson, BR, Fereday, S, Traficante, N, Alsop, K, Bowtell, DD, deFazio, A, Clifton-Bligh, R & Marsh, DJ 2016, 'The RING finger domain E3 ubiquitin ligases BRCA1 and the RNF20/RNF40 complex in global loss of the chromatin mark histone H2B monoubiquitination (H2Bub1) in cell line models and primary high-grade serous ovarian cancer', HUMAN MOLECULAR GENETICS, vol. 25, no. 24, pp. 5460-5471.View/Download from: Publisher's site
Wheate, NJ, Dickson, K-A, Kim, RR, Nematollahi, A, Macquart, RB, Kayser, V, Yu, G, Church, WB & Marsh, DJ 2016, 'Host-Guest Complexes of Carboxylated Pillar[n]arenes With Drugs', JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 105, no. 12, pp. 3615-3625.View/Download from: Publisher's site
Hahn, MA, Dickson, K-A, Jackson, S, Clarkson, A, Gill, AJ & Marsh, DJ 2012, 'The tumor suppressor CDC73 interacts with the ring finger proteins RNF20 and RNF40 and is required for the maintenance of histone 2B monoubiquitination', HUMAN MOLECULAR GENETICS, vol. 21, no. 3, pp. 559-568.View/Download from: Publisher's site
MacDiarmid, JA, Mugridge, NB, Weiss, JC, Phillips, L, Burn, AL, Paulin, RP, Haasdyk, JE, Dickson, KA, Brahmbhatt, VN, Pattison, ST, James, AC, Al Bakri, G, Straw, RC, Stillman, B, Graham, RM & Brahmbhatt, H 2007, 'Bacterially Derived 400 nm Particles for Encapsulation and Cancer Cell Targeting of Chemotherapeutics', Cancer Cell, vol. 11, no. 5, pp. 431-445.View/Download from: Publisher's site
Systemic administration of chemotherapeutic agents results in indiscriminate drug distribution and severe toxicity. Here we report a technology potentially overcoming these shortcomings through encapsulation and cancer cell-specific targeting of chemotherapeutics in bacterially derived 400 nm minicells. We discovered that minicells can be packaged with therapeutically significant concentrations of chemotherapeutics of differing charge, hydrophobicity, and solubility. Targeting of minicells via bispecific antibodies to receptors on cancer cell membranes results in endocytosis, intracellular degradation, and drug release. This affects highly significant tumor growth inhibition and regression in mouse xenografts and case studies of lymphoma in dogs despite administration of minute amounts of drug and antibody; a factor critical for limiting systemic toxicity that should allow the use of complex regimens of combination chemotherapy. © 2007 Elsevier Inc. All rights reserved.
Butt, AJ, Dickson, KA, Jambazov, S & Baxter, RC 2005, 'Enhancement of tumor necrosis factor-α-induced growth inhibition by insulin-like growth factor-binding protein-5 (IGFBP-5), but not IGFBP-3 in human breast cancer cells', Endocrinology, vol. 146, no. 7, pp. 3113-3122.View/Download from: Publisher's site
Expression of IGF-binding protein-3 (IGFBP-3) and IGFBP-5 in human breast cancer cells induces apoptosis and is associated with modulations in Bcl-2 proteins, suggesting that these IGFBPs induce an intrinsic apoptotic pathway. In this study we demonstrate that although both IGFBPs induced the activation of caspase-8 and caspase-9, the expression of IGFBP-5, but not IGFBP-3, sensitized MDA-MB-231 breast cancer cells to the inhibitory effects of TNFα. This sensitivity to TNFα was associated with a block in nuclear factor-κB-mediated cell survival signals. IGFBP-5 expression was also associated with a caspase-8-independent activation of Bid, increased levels of cytosolic second mitochondria-derived activator of caspase (Smac)/direct inhibitor of apoptosis proteins (IAP) binding protein with low pI (DIABLO), and an enhanced phosphorylation of c-Jun N-terminal kinase, both basally and in response to TNFα. These results suggest that IGFBP-5 expression may influence extrinsic apoptotic pathways via a differential modulation of downstream cell survival and cell death pathways. Furthermore, although IGFBP-3 and IGFBP-5 share much structural and functional homology, they can modulate distinct apoptotic pathways in human breast cancer cells. Copyright © 2005 by The Endocrine Society.
Butt, AJ, Martin, JL, Dickson, KA, McDougall, F, Firth, SM & Baxter, RC 2004, 'Insulin-like growth factor binding protein-3 expression is associated with growth stimulation of T47D human breast cancer cells: The role of altered epidermal growth factor signaling', Journal of Clinical Endocrinology and Metabolism, vol. 89, no. 4, pp. 1950-1956.View/Download from: Publisher's site
IGF binding protein (IGFBP)-3 has antiproliferative and proapoptotic effects on the growth of human breast cancer cells in vitro. However, clinical studies suggest that high levels of IGFBP-3 in breast tumor tissue are associated with large, highly proliferative tumors. In this study, we examined the effects of stable transfection with human IGFBP-3 cDNA on the growth of T47D human breast cancer cells in vitro and in vivo. Expression of IGFBP-3 initially inhibited the growth of T47D in vitro but was associated with enhanced growth in vivo. Furthermore, IGFBP-3-expressing cells in vitro became growth stimulated at higher passages post transfection, suggesting breast cancer cells may switch their response to IGFBP-3 with increasing tumorigenicity. These stimulatory effects observed in IGFBP-3-expressing cells were associated with an enhanced responsiveness to the proliferative effects of epidermal growth factor (EGF). When EGF receptor (EGFR) kinase activity was blocked using PD153035, high passage IGFBP-3 transfectants were growth inhibited compared with controls treated with inhibitor. These findings suggest that the interaction between IGFBP-3 and the EGFR system is central to whether IGFBP-3 acts as a growth stimulator or inhibitor in breast cancer cells and that therapies targeting EGFR may have increased efficacy in breast tumors expressing high levels of IGFBP-3.
Butt, AJ, Dickson, KA, McDougall, F & Baxter, RC 2003, 'Insulin-like growth factor-binding protein-5 inhibits the growth of human breast cancer cells in vitro and in vivo', Journal of Biological Chemistry, vol. 278, no. 32, pp. 29676-29685.View/Download from: Publisher's site
The role of insulin-like growth factor-binding protein (IGFBP)-5 in human breast cancer cell growth is unclear. We determined the effects of IGFBP-5 expression on the growth of human breast cancer cell lines in vivo and in vitro. Expression of IGFBP-5, both by stable transfection and adenoviral-mediated infection, was inhibitory to the growth of MDA-MB-231 and Hs578T human breast cancer cells over a 13-day period. IGFBP-5 expression resulted in a G2/M cell cycle arrest and the induction of apoptosis in both cell lines, an effect that was abrogated in the presence of the broad-spectrum caspase inhibitor, z-VAD-fmk. IGFBP-5-induced apoptosis was associated with a transcriptional increase in expression of the proapoptotic regulator bax and decrease in the anti-apoptotic bcl-2 compared with vector controls. Secreted IGFBP-5 when added exogenously to breast cancer cells was not internalized and had no effect on cell growth or apoptosis, suggesting that IGFBP-5 may elicit its inhibitory effects via a novel, intracrine mechanism. In athymic nude mice, stable expression of IGFBP-5 significantly inhibited both the formation and growth of tumors derived from MDA-MB-231 cells. IGFBP-5-expressing tumors also had a significantly elevated level of bax mRNA and decreased levels of bcl-2 mRNA compared with vector tumors. These data suggest that IGFBP-5 is a potent growth inhibitor and proapoptotic agent in human breast cancer cells via modulation of cell cycle regulation and apoptotic mediators.
Cole, AJ, Dickson, K-A, Clifton-Bligh, R & Marsh, DJ 2018, 'Abstract 3538: Targeting the E3 ubiquitin ligase RNF20 in ovarian cancer', Molecular and Cellular Biology / Genetics, Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL, American Association for Cancer Research.View/Download from: Publisher's site
Cole, AJ, Dickson, K-A, Liddle, C, Stirzaker, C, Clifton-Bligh, R & Marsh, DJ 2018, 'Abstract A06: Cisplatin-induced DNA damage modifies the chromatin landscape of histone H2B monoubiquitination in a p53-dependent manner', DNA Damage and Repair, Abstracts: AACR Special Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; October 1-4, 2017; Pittsburgh, PA, American Association for Cancer Research.View/Download from: Publisher's site
Cole, AJ, Dwight, T, Zhu, Y, Gill, AJ, Dickson, K-A, Clarkson, A, Gard, GB, Maidens, J, Valmadre, S, Clifton-Bligh, RJ & Marsh, DJ 2015, 'Assessment of TP53 mutation status in primary high-grade serous ovarian cancer and cell line models: Comparison between immunohistochemistry and next-generation sequencing.', CLINICAL CANCER RESEARCH, AACR Special Conference on Advances in Ovarian Cancer Research - Exploiting Vulnerabilities, AMER ASSOC CANCER RESEARCH, Orlando, FL.View/Download from: Publisher's site
Hahn, MA, Dickson, K-A, Jackson, S, Clarkson, A, Gill, AJ & Marsh, DJ 2012, 'Abstract 2167: The tumor suppressor CDC73/parafibromin is required for the maintenance of histone 2B monoubiquitination bothin vitroandin vivo', Molecular and Cellular Biology, Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL, American Association for Cancer Research.View/Download from: Publisher's site
Howell, VM, Dickson, K-A, Kan, CWS, Hahn, MA & Marsh, DJ 2012, 'Abstract 3150: miR-100 in ovarian cancer cell lines', Molecular and Cellular Biology, Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL, American Association for Cancer Research.View/Download from: Publisher's site