Profile of the month

Research Interest

Understanding the molecular causes of antinuclear antibodies (ANA)

ANA-positivity is a necessary criterion in the diagnosis of systemic lupus erythematosus (SLE) and, in heterogeneous specificity, is broadly associated with systemic autoimmune diseases, infections, cancers and aging. The causes for ANA is highly polygenic but, rare genetic deficiencies, e.g. C1q, C1r, C1s or C4, ANA and SLE disease are caused. In the last decade, we focused on the molecular mechanisms underlying ANA induction taking complement C1 deficiency as a model. Work so far suggest that the nucleus is intrinsically autoimmunogenic by containing alarmins. We recently identified a novel alarmin motif in the nucleolus (GAR/RGG) which defines a group of self-adjuvanted autoantigens. C1q binds to the nucleolus to cause its dismantling through activation of the C1r/C1s proteases. We currently investigate whether single autoantigens are sufficient to stage antinuclear autoimmunity.

Cancer vaccine development

The GAR/RGG alarmin motif was surprisingly discovered also to possess potent cell-penetrating peptide (CPP) activity. The GAR/RGG motif also carry cargo proteins across the membrane of dendritic cells into the cytoplasm. We have patented this technology and currently develop a vaccine platform focusing on cancer antigens. The basic ideas is that the GAR/RGG motif allows cancer antigens to access to cytoplasmic MHC I molecules to activate cancer-specific CD 8 T cells.