Research projects

Class I cytokine receptors

Members of the class 1 cytokine receptor family are important therapeutic targets in cancers, inflammatory bowel disease, osteoporosis, multiple sclerosis, and disorders related to blood cell formation, postnatal growth, obesity, lactation, and neural function. Loss or gain of function mutations in these receptors are known to lead to a wide variety of clinically important disorders. Class I cytokine receptors regulate a wide range of clinically relevant and cellular processes. This family contains around 30 members including receptors for erythropoietin (EPO), prolactin (PRL), growth hormone (GH), thrombopoietin (TPO), granulocyte-macrophage colony-stimulating factor (GM-CSF), leukaemia inhibitory factor (LIF), interleukin-3 (IL-3), IL-5, and IL-6. Despite great progress in elucidating the structural details of ligand binding to the extracellular domain of receptors for several members of this family, the means by which these receptors activate their associated JAK kinases to initiate signalling has remained elusive. Recently we elucidated the mechanism of action of the archetypal class I cytokine receptor, the GH receptor (GHR), in unprecedented detail (published in Science 2014). Next we plan to determine if the same or similar mechanism exist for the related homodimeric and heterodimeric cytokine receptors. By utilising this new molecular understanding we will develop potential therapeutic molecules by targeting a novel region of these cytokine receptors. 

  • Understanding the mechanism of cytokine receptor activation
  • Understanding the mechanism of the JAK2 kinase activation
  • How mutations in cytokine receptor signalling pathways contribute to cancer

Student opportunities

  • Defining the molecular mechanism of JAK2 activation by the EPO receptor
  • Molecular mechanism for activation of Src by the Growth Hormone receptor.
  • Defining the molecular mechanism of JAK2 activation by the Prolactin receptor
  • Defining the molecular mechanism of JAK2 activation by the GM-CSF receptor
  • Defining the molecular mechanism of JAK2 activation by the IL-6 receptor

Contact: a.brooks@uq.edu.au

Researcher biography

Dr Andrew Brooks is the Group Leader of the Cytokine Receptor Signalling Group at the University of Queensland Diamantina Institute (Australia) within the Translational Research Institute. Andrew completed his Honours research on Flaviviruses in 1996 at the Department of Microbiology and Immunology at James Cook University and then moved to the Department of Biochemistry to study Dengue Virus where he completed his PhD in 2002. He then moved to St Jude Children's Research Hospital in Memphis, TN, USA where he researched the role of Epstein-Barr Virus in B-cell lymphomagenesis. He then joined the research group headed by Prof Michael Waters in 2006. Andrew's research interests are in cytokine receptors, cell signalling, immunology, and oncogenesis. His current research focus is on the molecular mechanisms of class I cytokine receptor activation including the growth hormone receptor (GHR), erythropoietin receptor (EpoR), thrombopoietin receptor (TpoR/MPL), granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR), and IL-6 receptor (IL-6R). This research has led to publications in journals including Science, Nature Cell Biology, PNAS, and Molecular Endocrinology. He has been the recipient of over $3.1 million in research grant funding (over $1.6 million as CIA/primary investigator) and has a number of national and international collaborations. Andrew is an Editorial Board member for the Journal JAK-STAT and Review Editor for Molecular and Structural Endocrinology for the Journal Frontiers in Endocrinology. He has been a committee member of Australian Early-Mid Career Researchers Forum (AEMCRF) launched by the Australian Academy of Science.

Areas of research