dr. Fabian Fischer (PhD)

Nucleic acids (NA) predominantly exist in their right-handed A- (RNA) or B- (DNA) conformations. Under certain conditions, such as viral infections, high salt concentrations or certain chemical stimuli, they can additionally adopt an energetically unfavorable Z-conformation. Z-NAs can be sensed by two mammalian proteins: ADAR1 and ZBP1. While ADAR1 binding to Z-NAs prevents inflammation onset, ZBP1 binding activates it. ZBP1 binds Z-NAs via two dedicated N-terminal Z domains and induces downstream signaling cascades via its C-terminal RHIM domains and subsequent homotypic protein-protein interactions with other RHIM-containing proteins. ZBP1 activation results in activation of regulated cell death pathways, such as apoptosis and necroptosis, and ultimately removal of the activated or compromised cell.

While ZBP1 activation through chemical compounds such as CBL0137 has shown promising results in alleviating melanoma burden in mice, ZBP1 expression in human multiple myeloma cell lines has been linked to myeloma cell survival and proliferation. The activation mechanisms of ZBP1, its regulatory partners, and decision making for downstream signaling pathways remain poorly understood. Therefore, I investigate ZBP1 biology with the aim of creating a more detailed understanding of these signaling mechanisms in the short term, and leverage these findings to modulate ZBP1-related pathologies in the long term.
 

• Lab address
  Vandenabeele Unit - Molecular Signaling and Cell Death
  VIB-UGent Center for Inflammation Research
  Nucleic acid immunity lab - Jonathan Maelfait lab
  Fiers-Schell-Van Montagu building
  Technologiepark-Zwijnaarde 71
  B-9052 Ghent, Belgium
• Maelfait lab
• Linkedin
• ORCID
• Fabian Fischer is interested to receive invitations for presentations or talks