Molecular Medicine

Research in Molecular Medicine:

The focus of our research is to define precisely how chronically activated T cells contribute to inflammatory disease in man.

In recent years we have focussed our efforts on studying the switch from antigen-driven signals to cytokine-dependent signals during terminal T cell differentiation. We have studied how TCR signalling pathways are uncoupled in chronic inflammation, and have defined some of the mechanisms involved in attenuating transcription of cytokine genes, such as IL-2.

We have also identified a unique biochemical and molecular fingerprint of chronic TNF-R signals in T cells that may be sufficient to promote effector function in the absence of specific antigen signals.

More recently we have developed novel proteomic approaches for dissecting the pathways involved in T cell - macrophage cell contact-dependent signalling.

Background:

The acquisition of transcriptional competence for cytokine gene expression is a defining checkpoint in the differentiation of CD4+ effector T cells.

This process is initiated by combined antigen and cytokine receptor stimulation coupled to signalling pathways and transcription factors acting coordinately, regulated to induce cell differentiation and specialised patterns of gene expression.

These gene expression profiles ultimately dictate T cell effector function and are central to host immunity and the regulation of inflammatory responses.

While the early stages of T cell differentiation of T helper subsets are well characterised at the moleculat level, the signalling pathways that promote terminal differentiation and effector responses at sites of chronic inflammation are less well understood.