Signal Transduction

The Signal Transduction Laboratory researches DNA damage signalling and repair pathways and their impact on cancer susceptibility through preventing DNA mutations. These studies have significant relevance to both basic biology (e.g. understanding the process of cell division, repair of DNA damage and mechanisms of ageing) and clinical medicine (e.g. effect on drug efficacy).

Several genes involved in the DNA damage response pathways are known to contribute to breast cancers. This group seeks to identify other known or new genes in these pathways which might have similar involvement in cancer susceptibility by preventing mutations in our DNA. This area is of critical importance to cancer research as the pathway controlling the DNA damage response are involved in tumour suppression and are believed to be mutated at the early stage in the evolution of cancer.

CURRENT RESEARCH

  • to understand the role of Cep55 in cancer initiation and progression using overexpression mouse models
  • to elucidate the pathophysiological role SSB1 and SSB2 using knockout mouse models
  • to functionally characterise SSB1 and SSB2 interacting proteins
  • to understand the role of Centrobin in the regulation of microtubule dynamics
  • to perform pathway profiling in breast cancer for development of targeted therapies
  • development of novel combination treatments against cancer in animal models including specific pathway inhibitors and targeted drug delivery
  • understanding the cellular and molecular factors which determine the extent of tumour response to therapy including proliferation, apoptosis, DNA-repair, and cell cycle
  • DNA damage

Staff

  • Dr Murugan Kalimutho, Senior Research Officer
  • Dr Prahlad Raninga, Research Officer
  • Dr Devathri Nanayakkara, Research Officer
  • Dr Mariska Miranda, Research Officer
  • Dr Rahul Srivastava, Research Officer
  • Dr Behnam Rashidieh, Research Officer
  • Xue Lu, PhD student
  • Ashny Ali, PhD student
  • Simon Tria, Honour’s student
  • Sivanandhini Sankarasubramanian, Master’s student
  • Uma Raghupathi, Master’s student
  • Stephen Miles, Scientific Technical Officer

We gratefully acknowledge financial support of

  • Australian Research Council
  • Australian Cancer Research Foundation
  • National Breast Cancer Foundation
  • National Health and Medical Research Council
  • Cancer Council Queensland
  • Susan G. Komen for the Cure Research Program

STUDENT PROJECTS

Expanding the scope of PARPi for treatment of high-grade serous ovarian cancers

Suitable for Honours or PhD students. In Australia, approximately 1600 women are diagnosed with ovarian cancer each year and the majority have high-grade serous ovarian type (HGSOC). The five year survival rate for ovarian cancer is currently just 41% and lags well behind breast (91% survival) and other cancers. Notably, resistance to standard of care […]

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Targeting CEP55 in triple-negative breast cancer

Suitable for Honours or PhD students. Breast cancer in females has now passed lung cancer as the most common diagnosed cancer. It affects over 10% of women before the age of 85, placing an enormous burden on our healthcare system. Despite some spectacular recent successes in fighting breast cancer with new treatments (e.g., immune checkpoint […]

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To understand mechanisms that mediate chemo-/radioresistance of breast cancer stem cells

Suitable for Honours or PhD students. Precursor metastatic cells, referred to as ‘cancer stem cells’ (CSCs), play a pivotal role in metastasis and relapse in breast cancer (BC) patients. Thus, effective management of breast cancer will require new therapeutic strategies that eliminate CSCs. Nonetheless, drugs that specifically target CSCs are extremely under-developed. We have made […]

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Decipher the role of a new epigenetic modulator, RLF, in replication stress response

Suitable for Honours or PhD students. Uncontrolled cell proliferation, a hallmark of tumour cells, leads to high levels of replication-related lesions and double strand breaks (DSBs). As a survival strategy, some cancers have elevated activity of the Homologous Recombination (HR) pathway, the main pathway repairing DSBs arising from replication stress, or promote other error-prone repair […]

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Repurposing an FDA-approved drug to treat mut-p53 cancers

Suitable for Honours or PhD students. TP53 is the most frequently mutated gene, with over half of all human tumours harbouring mutation of this gene. Unlike the majority of tumour suppressor genes that are inactivated as a result of truncating mutations, the majority of TP53 mutations are missense, resulting in accumulation of mutant protein and […]

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