Brooks Group - Cytokine receptor signalling

About

Our group has two main focus areas: 

1. We study the mechanisms of cytokine receptor activation and their contribution to a diverse range of diseases. In addition we identifiy novel molecules that specifically target cytokine receptor signalling. 
2. We study the role of the immunotolerance molecule HLA-G and its effects in regulating inflammation in liver regeneration and inflammatory disease states.

Members of the class I 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). Our current work extends to understanding how Src family kinases are activated by cytokine receptors, mechanisms that cause dysregulated cytokine receptor signalling in disease, and indentifing novel molecules to target cytokine receptor signalling.

HLA-G is nonclassical MHC class I that has binds receptors to inhibit the activation of a range of immune cells. HLA-G expression can be activated by some cytokines and has been shown to play an important role in regulating inflammation.

In our laboratory, we use techniques of gene modification and gene delivery to study the role of specific proteins in cellular signalling processes, combined with a range of microscopy and biochemical methods to discover how proteins interact and function as well as determine the role of oncogenic mutations. We are investigating the role of cytokine receptors, their associated signalling proteins, and mechanisms that regulate these signalling pathways. In addition we study the role of HLA-G in regulating inflammation at the cellular level and in vivo.