PhD Researchers
MS ANGELA CHO

Programme: TCE Glioblastoma

TCE Leader:

Associate Professor Michael Back; Director, Radiation Oncology, RNSH;  Associate Professor, USyd

Dr Helen Wheeler; Head Medical Oncology, RNSH

Associate Professor Mustafa Khasraw; Oncology Senior Research Fellow and Clinical Lead NHMRC CTC, USyd; Medical Oncologist, RNSH

Aims

To improve treatments for patients with glioma

Current Research Status

January 2018

  • Identified 13 genes and 7 proteins which may play a role in promoting brain tumour progression and therapy resistance in a discovery cohort of patients
  • Obtain governance approval for ethics to obtain brain tumour tissue from the Kolling tumour Bank

August 2018

  • Validate the 13 genes and 7 proteins of interest in a larger cohort of patients using brain tumour tissue from the Kolling Tumour Bank
  • Determine whether the genes and proteins of interest are true indicators of glioma aggression
  • Develop radio-resistance in three human brain cancer cell lines using the SAARP
MS MARTHE CHEHADE

Programme: ACC (Adenoid Cystic Carcinoma)

TCE Leaders:

Professor Stanley Sidhu; Professor of Surgery and Head of the University of Sydney Endocrine Surgical Unit

Aims

  • Developing a model of stable PRINS enriched ACC and breast cancer cell lines using CRISPR Cas9 technology
  • Gain of function studies of PRINS in stable PRINS enriched ACC and breast cancer cell lines
  • Identification of clinical correlates of PRINS expression in breast cancer clinical samples
  • Investigation of the mechanisms underlying PRINS’s cellular effect (A Nucleophosmin,B I nterleukin-6)
  • In vivo studies

Current Research Status

July 2018

  • Ligation and cloning of PRINS sequence into CRISPR donor vector
  • CRISPR transfection of H295R and MCF-7 cell lines
  • Provisional approval from Kolling Tumour Bank to use breast cancer samples for clinical study granted. Awaiting access to samples to proceed with the study.
  • Awarded Round 8 Sydney Vital Research Scholarship with the aim of investigating the interaction between PRINS and interleukin-6 in-vitro in ACC PRINS enriched stable cells.

August 2018

  • PhD suspended for the next 3 months for maternity leave.
  • Collate clinical information from histopathology reports from Tumour Bank.

November 2018

  • Single colony selection using limiting dilution cloning in the CRISPR PRINS enriched cells (allow 1-2 months for colony selection, growth and confirmation using sequencing).
  • Once stable cell lines have been established, commence phenotypic studies to satisfy Aim 2.
  • RNA extraction from breast cancer clinical samples.
MS GRACE LIM

Programme: TCE Thyroid

TCE Leaders:

Professor Anthony Gill; Senior Staff Specialist, RNSH; Professor of Pathology, USyd

Associate Professor Roderick Clifton-Bligh; Senior Staff Specilast and Head Department of Endocrinology, RNSH; Associate Professor of Medicine, USyd

Professor Mark Sywak; Endocrine Surgeon, RNSH; Clinical Associate Professor, USyd

Aims

  • Mechanistic phase: regulation of telomerase activity will be comprehensively defined in thyroid cancer cell lines and clinical samples (telomerase activity correlated to TERT mutations and expression of TERT, TERC and TERRA; and chromatin structure of TERTp defined).
  • Discovery phase: THYTERT/LUC cells will be used in a drug discovery screen using 3707 compounds. Data will be analyzed according to EC50 and maximal inhibition of luciferase. Lead compounds will be validated in THYTERT/LUC cells and a broad range of thyroid cancer cell lines.
  • Pre-clinical phase: lead compounds identified in the initial phase above will be progressed into mouse xenograft models of thyroid cancer to validate clinical efficacy in vivo.
  • Extension phase: LUC will be CRISPR-engineered to replace TERT upstream of its endogenous promoter in glioblastoma T98G cells. Clones of stably integrated cells will be identified, and subject to the assay pipeline described above.

Current Research Status

January-July 2018

  • Awarded the Sydney Vital Research Scholar Award for research investigating the utility of targeting telomerase by Aurora Kinase inhibitors in advanced thyroid cancer.
  • Establishing the optimal dose of Aurora Kinase inhibitors in a panel of thyroid cancer cell lines.
  • Functional experiments exploring the effects of TERT inhibition in tumorigenic processes such as dysregulated cell cycle progression and anti-apoptotic pathways.
  • Determining telomerase activity and telomere length in response to treatment.

August-November 2018

  • Elucidating the biological mechanism of action by which Aurora Kinase inhibitors dysregulate the oncogenic function of TERT.
  • Exploring combination treatment regimens in thyroid cancer, by treatment with both Aurora Kinase inhibitors and the currently used drugs in advanced thyroid cancer, like Sorafenib and Lenvatinib.
  • Establishing an improved optimal dose of combination treatment.
  • Functional experiments from combination treatments in the thyroid cancer cells in its effect in TERT inhibition; tumorigenic processes, telomerase activity and telomere length assays.
MR JOSEPH XAVIER

Programme: TCE Pancreatic Cancer

TCE Leaders

Professor Stephen Clarke; Director, Cancer Services, RNSH; Professor of Medicine, USyd

Associate Professor Anubhav Mittal; Pancreatic and General Surgeon, RNSH, NSP; Conjoint Senior Lecturer, USyd

Professor Jaswinder Samra; HPB and General Surgeon, RNSH; Clinical Professor, USyd

Aims

  • To better understand/demonstrate the complex intra-pancreatic vascular network and variant vascular supply of the pancreas
  • To model guided pancreatic resection based on vascular anatomy
  • To evaluate the efficacy of anti-oxidants and anti-proteases in reducing or preventing post-operative pancreatitis

Current Research Status

February – April 2018

  • Conduct a systematic review to identify candidate medication that may help ameliorate post-operative pancreatitis – examining specifically the literature for acute pancreatitis and post-pancreatic transplant pancreatitis
  • Continue to collect data on post-operative pancreatitis on a clinical cohort of patients at RNSH and NSPH
  • Conduct cadaveric and animal studies to better understand the intra-pancreatic microvascular networks and identify the likely watershed area in the neck of of the pancreas where the gland is usually divided during surgery – thereby making this area more susceptible to postoperative pancreatitis

May – July 2018

  • Analysis of data obtained in the previous few months
  • Formative planning of the next in-vivo stage of my project

August-October 2018

  • Establish a detailed and stable rodent model of post-operative pancreatitis
  • Evaluate candidate anti-oxidant and anti-protease medication in the prevention of post-operative pancreatitis in the above mentioned model.
  • Continue the work on human intra-pancreatic vascular anatomy using indocyanine green angiography

November – January 2019

  • Data collection and collation of next manuscripts
MS ELIZABETH HUTCHINGS

Programme: Breast Cancer

TCE Leaders:

Professor Frances Boyle; Diretor Patricia Ritchie Centre for Cancer Care and Research, Mater Hospital; Professor of Medical Oncology, USyd

Professor Andrew Spillane; Surgeon,Mater Hospital, , Professor of Surgical Oncology, USyd

Aims

Primary objective

  • To assess the attitudes of patients to the secondary use of routinely collected administrative and clinical trial breast cancer data.

Secondary objectives

  • To assess the attitudes of clinicians/oncology researchers to the secondary use of routinely collected administrative and clinical trial breast cancer data.
  • To assess the attitudes of other key personnel to the secondary use of routinely collected administrative and clinical trial breast cancer data.
  • To assess the role of secondary data analysis in influencing the design of breast cancer clinical trials.

Current Research Status

September 2017-June 2018

  • Formative planning of research phases
  • Developed protocol and completed systematic literature review
  • Developed protocol and supporting documentation for semi-structured interviews
  • Ethics application for semi-structured interviews completed

July 2018- December 2018

  • Analyse results of systematic literature review, submit for publication.
  • Conduct semi-structured interviews
  • Develop protocol / ethics applications for the online questionnaires and focus groups
  • Analyse results of the semi-structured interviews

2019-2020

  • Conduct and analyse results of the online questionnaire
  • Conduct and analyse results of the focus groups
  • Ethics application for a Delphi consensus process
  • Run Delphi Consensus process
  • Publish results of the Delphi consensus process Research Status
  • Publish results of the online questionnaire and focus groups