Yeesim Khew-Goodall
Adelaide Medical School
Faculty of Health and Medical Sciences
Professor Yeesim Khew-Goodall
Head, Cell Signalling Laboratory,
Centre for Cancer Biology, an alliance of SA Pathology and University of South Australia
Qualifications: B.Sc. (Adelaide), PhD (Adelaide)
Professor Yeesim Khew-Goodall's earlier work on epithelial-mesenchymal transition (EMT) has led to a seminal publication identifying critical signalling pathways, including the roles of microRNAs, in cell plasticity and cellular programming. She is internationally known for her pioneering studies and subsequent studies on EMT and for unraveling novel phosphorylation-driven signalling pathways in cancer.
Although targeted therapy for many cancers has made huge progress in recent years, triple negative breast cancer in women and the childhood cancer, neuroblastoma, lag behind many other cancers in this aspect. Her laboratory now focuses on studies to identify signalling pathways that are dysregulated in cancer that drive cell growth and survival – to discover new biomarkers and therapeutic targets for cancers that lack reliable targeted therapy, including triple negative breast cancer and neuroblastoma, and to elucidate the mechanisms underlying therapy resistance.
We investigate the roles of post-translational modifications of proteins, microRNAs and lncRNAs using a range of cutting-edge technologies – including RNAseq, single cell Seq, spatial transcriptomics and bioinformatics (in collaboration with Prof Greg Goodall’s group), CRISPR gene editing, high resolution microscopy, proteomics, structural biology, iPSC modelling of disease and disease relevant mouse models – to unravel disease-driving molecular mechanisms.
We offer students a wide range of projects that span cutting-edge research technologies.
Location: Centre for Cancer Biology
My research is currently focussed in triple negative breast cancer and neuroblastoma.
Project 1. Triple negative breast cancer (TNBC) (supervised by Prof Khew-Goodall and Dr Ana Lonic) is breast cancer that lacks oestrogen and progesterone receptors and has no HER2 amplification. As such, to date, unlike the other forms of breast cancer, there is a paucity of reliable targeted therapy to treat triple negative breast cancer and chemotherapy remains the standard of care. However, whilst many patients respond well to chemotherapy, about a quarter to a fifth of patients become resistant to chemotherapy and there are few reliable treatment options thereafter. Consequently, there is a need to understand the underlying causes of chemoresistance in triple negative breast cancer.
Our recent studies have identified a signalling pathway – the Fer-PKCδ-PTPN14 axis – that is dysregulated in about 25-30% of triple negative breast cancer patients. Dysregulation of this pathway leads to increased secretion of pro-metastatic factors (Belle et al., 2015), as well as increased oncogenic signalling and better cell survival due to aberrant receptor trafficking (Lonic et al., 2021).
Honours and HDR projects include:
• Investigating how this pathway affects the response of triple negative breast cancer to current treatments, including its role in influencing both the fate of the cancer cells and the tumour microenvironment.
• identifying the molecular mechanisms by which this pathway mediates it effects, including identification of kinase substrates and new (previously under-appreciated) roles of post-translational modifications on kinase functions.
• investigating how dysregulation of the endosomal trafficking mechanisms can lead to cancer progression.
Our laboratory uses phosphoproteomics, functional genomics, spatial transcriptomics, high/super resolution confocal microscopy, genetically modified or xenograft mouse models of triple negative breast cancer and patient breast cancer specimens, as appropriate, for our studies.
Project 2. Neuroblastoma (supervised by Prof Khew-Goodall). Neuroblastoma is a childhood cancer that particularly affects very young children under the age of five, with a median age of diagnosis around one-and-a-half to two years of age. It is a highly heterogeneous cancer of the sympathetic nervous system with some unusual properties that are poorly understood. These include some children with stage 4 cancers that can spontaneously regress without treatment, yet others do not respond to treatment. The lack of reliable targeted therapy for neuroblastoma also means that these children are routinely treated with chemotherapy. However, because of the young age of these patients, even if they recover from the cancer, they can often suffer life-long debilitating outcomes. Our studies are based on the hypothesis that neuroblastoma arise from a failure of complete differentiation of the trunk neural crest cells to sympathetic neurons and it is the intermediate, incompletely differentiated neuroblasts that go on to become cancerous.
Honours and HDR projects:
• will take the approach of understanding the process of differentiation and maturation of neuroblasts to sympathetic neurons to identify critical signalling pathways of the differentiation and maturation program, using induced pluripotent stem cells (iPSCs).
• use data on neuroblast differentiation to identify and understand how dysregulated signalling pathways can lead to neuroblastoma in patients.
• Using CRISPR-edited iPSCs to model the disease to identify potential new therapeutic targets.
These studies will be carried out using state-of-the-art sequencing strategies for coding and non-coding RNAs, bioinformatics and spatial transcriptomics using mouse embryos and patient samples. These studies are part of a large collaborative team which includes those of Associate Professor Quenten Schwarz and Professor Greg Goodall at the Centre for Cancer Biology.
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Appointments
Date Position Institution name 2013 - ongoing Adjunct Professor University of South Australia 2005 - ongoing Affiliate Titleholder University of Adelaide 1990 - ongoing Medical Scientist (Research) SA Pathology -
Education
Date Institution name Country Title University of Adelaide Australia PhD University of Adelaide Australia B Sc (Hons) -
Postgraduate Training
Date Title Institution Country Postdoctoral Fellow Roche Institute of Molecular Biology United States Postdoctoral Fellow Friedrich Miescher Institute Switzerland -
Research Interests
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Journals
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Conference Papers
Year Citation 2018 Bottini, A., Wu, D. J., Ai, R., LeRoux, M., Bartok, B., Bombardieri, M., . . . Bottini, N. (2018). Non-Receptor Protein Tyrosine Phosphatase 14 (PTPN14) Promotes YAP-Dependent Tgfbeta Signaling in RA FLS. In ARTHRITIS & RHEUMATOLOGY Vol. 70 (pp. 1 page). IL, Chicago: WILEY. -
Conference Items
Year Citation 2015 Hissaria, P., Bert, A., Proudman, S., Goodall, G., & Khew-Goodall, Y. (2015). DIFFERENTIAL PATTERN OF MICRORNA EXPRESSION IN LIMITED AND DIFFUSE CUTANEOUS VARIANTS OF SYSTEMIC SCLEROSIS - A POSSIBLE MECHANISM TO EXPLAIN THE UNIQUE CLINICAL PHENOTYPES. Poster session presented at the meeting of INTERNAL MEDICINE JOURNAL. WILEY-BLACKWELL. 2015 Hissaria, P., Bert, A., Proudman, S., Goodall, G., & Khew-Goodall, Y. (2015). MICRO RNAS (MIRNAS) INVOLVED IN TGF BETA SIGNALLING PATHWAYS ARE DIFFERENTIALLY EXPRESSED IN THE PAPILLARY DERMIS OF INVOLVED SKIN IN LIMITED AND DIFFUSE CUTANEOUS SCLERODERMA PATIENTS. Poster session presented at the meeting of INTERNAL MEDICINE JOURNAL. WILEY-BLACKWELL. 2013 Khew-Goodall, Y. (2013). A NOVEL REGULATOR OF THE SECRETOME MODULATES CANCER METASTASIS. Poster session presented at the meeting of CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY. Hangzhou, PEOPLES R CHINA: WILEY-BLACKWELL. 2010 Crocker, L., Gregory, P., Goodall, G., & Khew-Goodall, Y. (2010). MICRORNAS REGULATING FIBROBLAST ACTIVATION AND EPITHELIAL MESENCHYMAL TRANSITION IN FIBROSIS. Poster session presented at the meeting of WOUND REPAIR AND REGENERATION. WILEY-BLACKWELL. 2008 Gregory, P. A., Bracken, C. P., Bert, A. G., Paterson, E. L., Kolesnikoff, N., Farshid, G., . . . Goodall, G. J. (2008). Role of the miR-200 family in mediating EMT in response to TGF-β. Poster session presented at the meeting of Abstracts and Reviews of 7th Joint Conference of the International Cytokine Society and the International Society for Interferon and Cytokine Research, as published in Cytokine. Montreal, Canada: Elsevier.
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Current Higher Degree by Research Supervision (University of Adelaide)
Date Role Research Topic Program Degree Type Student Load Student Name 2020 Principal Supervisor Identifying pY374-PKC-delta substrates that control endosomal trafficking of receptor tyrosine kinases Doctor of Philosophy Doctorate Full Time Miss Winona Faye Onglao -
Past Higher Degree by Research Supervision (University of Adelaide)
Date Role Research Topic Program Degree Type Student Load Student Name 2010 - 2012 Co-Supervisor The miR 200 Family is Controlled by Epigenetic based Mechanisms and Mediates Transition Between Non Stem and Stem like Cell Phenotypes Doctor of Philosophy Doctorate Full Time Mr Yat Yuen Lim 2006 - 2011 Principal Supervisor Tyrosine Phosphatase Pez: A Novel Regulator of TGFß Signalling, Epithelial-Mesenchymal Transition and Protein Secretion in Development and Cancer Doctor of Philosophy Doctorate Full Time Mrs Leila Belle 2006 - 2010 Co-Supervisor Downregulation of the MicroRNA-200 Family Induces Epithelial to Mesenchymal Transition Doctor of Philosophy Doctorate Full Time Miss Emily Paterson 2004 - 2009 Principal Supervisor A Novel Proinflammatory Role for Annexin A1 in Neutrophil Transendothelial Migration Doctor of Philosophy Doctorate Full Time Ms Samantha Louise Williams 1998 - 2003 Principal Supervisor Protein Tyrosine Phosphatase Pez: Its role in the regulation of cell-cell adhesions Doctor of Philosophy Doctorate Full Time Ms Carol Wadham
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