Dr Timothy Hercus

Work history

The principal focus of my research is to understand the mechanisms of cytokine receptor assembly and activation that underpin the pleiotropic functional properties of the beta common (βc) family of cytokines, GM-CSF, IL-3 and IL-5, on populations of human blood cells. These cells and the cytokines that regulate their survival and activity, are vital for a range of immune functions. Disruption of normal cytokine function is associated with inflammatory disease as well as cancer, particularly leukaemia. An important translational aspect of this work is to develop and characterise novel agents such as monoclonal antibodies, that can block or modulate the activities of these cytokines, thereby identifying molecules with potential therapeutic utility.

My recent research has been directed towards discovering how the cytokines GM-CSF and IL-3 interact with their receptors and how this interaction leads to receptor activation and gives rise to complex (pleiotropic) signalling outcomes. Detailed understanding of this process is essential for the development of targeted agents that can block or modulate receptor activation. I initially worked as a Research Assistant/PhD student with Dr Frances Shannon and Dr Angel Lopez (IMVS, Adelaide), 1988-1994, studying the structure/function properties of GM-CSF. The potent GM-CSF antagonist (GM E21R) was a key discovery arising from this work and from 1994-1998, I continued to characterise this molecule in post-doctoral studies with Dr Lopez. From 1998-2002 I was employed by BresGen Ltd as a Senior Research Officer working on the clinical development of GM E21R for therapeutic applications. This work involved pharmacokinetic studies, analysis of anti-GM E21R antibodies, GM E21R functional studies and quality control protocols to support pre-clinical and clinical trials. Since 2003, I have worked as a Senior Research Officer and Team Leader in the Cytokine Receptor Laboratory (CRL) located at the Centre for Cancer Biology (CCB) with Prof Angel Lopez. In collaboration with Prof Michael Parker (Bio21 Institute, Melbourne), we have studied the structure of the GM-CSF and IL-3 receptor complexes. During this time, we determined structures for 9 distinct ligand/receptor complexes, including those containing inhibitory antibodies, published 18 manuscripts and made seminal discoveries about the unique receptor activation mechanism used by the bc cytokines.

Prior to undertaking my PhD studies, I worked as a Research Assistant with Prof RH Symons (Biochemistry Department, Adelaide University), 1986-1987. During this time, I sequenced fragments of the Soybean Dwarf Virus genome and identified, sequenced and characterised a self-cleaving satellite RNA associated with Barley Yellow Dwarf Virus. During the period 1987 – 1988, I worked as a Research Assistant with Dr J Walker (Nobel Prize in Chemistry, 1997, Laboratory of Molecular Biology, Cambridge England), studying an ovine model for ceroid lipofuscinoses and sequencing the human T2 translocase gene.