Pathogenesis of STAT1 gain-of-function and evaluation of gene therapeutic approaches.

Primary immunodeficiencies (PIDs) have provided crucial information
for the elucidation of immunological pathways. Although many causal
mutations in PID patients have been identified, the exact
pathogenesis often remains to be elucidated and clues for an
individualized therapeutic approach remain absent. In this project we
focus mainly on adult patients with a proven primary
immunodeficiency due to STAT1 gain-of-function mutations. We
explore in depth the pathophysiology of STAT1 gain-of-function using
novel real-time imaging techniques ex vivo. Finally, we setup a
platform for evaluation of gene therapeutic approaches for
monogenic, rare, PIDs in adults. Thereby, we hope to answer
an unmet need: personalized medicine for rare diseases
accompanied by significant morbidity and mortality, currently lacking
rationalized and/or etiological treatment options.