Mouldy Sioud

Research in the group is directed towards RNA interference, immune responses in cancer patients, vaccine design, and antigen expression strategies, seeking for new therapeutic strategies and markers for diagnosis and/or prognosis


*Among the tools for silencing gene expression, are techniques that inhibit the expression of specific proteins by using various nucleic acid-based approaches such as ribozymes, DNAzymes, and small interfering RNAs (see Sioud, Trends Pharmacol Sci. 2004, for review). Notably, targeting mRNAs provides a specificity and efficiency of drug design not available with other anti-gene techniques. Furthermore, it allows for the selective inhibition of closely related genes such as isoenzymes. To translate RNA interference technology into the clinic as a form of immuno- and gene-therapy, we are interfering with (i) the properties of immune cells such as dendritic cells and regulatory T cells to enhance tumour immunity,(ii) to beack self-tolerance against tumour cells, and (ii) to target the interplay between stromal and tumour cells.

*The possibility of selecting ligands from large random peptides or protein libraries expressed on phages or bacteria has raised an important interest for defining B and T cell specificities. We reasoned that the pool of circulating antibodies from patient sera would contain the repertoire of antibodies elicited against, for example, tumour cells and/or self-proteins (see Sioud, Clin Immunol Immunopathol. 1996, for review). Probing such specific immune responses in cancer patients with phage display technologies is expected to facilitate diagnosis, prognosis, and/or vaccine design.

*Epitope mimicry and anti-tumour immunity. Although the exact mechanisms mediating the initiation of autoimmune diseases are unknown, sequence similarity between infectious agents and self-proteins (epitope mimicry) has been proposed as the main initating mechannism (see Sioud et al, Immunology, 1995). Previously, we have shown that this concept of epitope mimicry can trigger specific autoimmune responses against tunmour cells (see Sioud 2002, Mol. Med 8: 115-119, for review). We are currently exploring this strategy and its derivates to beack tolerance and induce an effective immunity against tumour cells.

*Several innate receptors play central roles in immune responses by recognizing conserved structural patterns in diverse microbial molecules. In addition to infection, our understanding of innate immunity is crucial for improving cancer vaccines and designing safe therapies (see Sioud Trends Mol Med. 2006, Nat Biotechnol. 2006, for reviews).

Links:
Frontiers in Bioscience: special issue

A top quality book on siRNA and miRNA gene silencing

Key publications