Andrew Lew-Projects

Andrew Lew-Projects

Projects

Targeting survival of dendritic cells as a potential treatment of autoimmune diseases

Dendritic cells (DCs) are critical for orchestrating an immune response whether to fight infection or to precipitate autoimmune disease. We found that IFN-a producing plasmacytoid DCs (pDCs) rely heavily on anti-apoptotic BCL-2 for survival. Accordingly, BCL-2 antagonists selectively kill pDCs.

We are investigating whether BCL-2 antagonists could reduce the generation of autoimmune responses and thus opens a new avenue for treatment of pDC-involved diseases such as systemic lupus erythematosus. We are also investigating how other anti-apoptotic molecules impact on the survival of DC subsets

Programmed necrosis as a physiologically important death mechanism for activated T cells

T cells confer immunity against pathogens but can also cause autoimmunity when dysregulated. We showed recently that a new type of cell death mediated by a key molecule is particularly important for death of activated T cells but not naïve T cells.

We hypothesise that inhibiting this pathway will boost immunity to pathogens, whereas promoting it  will selectively kill pathogenic T cells without purging naïve T cells. We are investigating:

  • Molecular regulators of this pathway.
  • Contribution of this pathway to induction of anti-pathogen immunity.
  • Impact of inhibition of this pathway on pathogenic T cells in type 1 diabetes and coeliac disease.