Ann Marshak-Rothstein

Lecture Title: Endosomal vs Cytosolic Nucleic Acid Sensors in Autoinflammation

AMR obtained her PhD from the University of Pennsylvania and then completed postdoctoral training at MIT. She then moved to Boston University Medical School as faculty in the Department of Microbiology before moving to UMass Chan Medical School in 2009 where she is currently a Professor of Medicine in the Division of Rheumatology. Her main research interests have focused on the role of nucleic acid sensing receptors in murine models of autoimmunity and autoinflammation. Her lab first showed that endosomal TLRs can detect mammalian (and not just microbial) nucleic acid ligands. These studies demonstrated that endogenous nucleic acids serve as self-adjuvants in the context of autoreactive B cell activation and explained why so many autoantibodies target either nuclear or cytosolic nucleic acid binding proteins. She has subsequently gone on to identify distinct roles for TLR9 and TLR7 in a variety of autoimmune and autoinflammatory diseases. She has also gone on to explore the role of nucleic acid sensors in mice deficient for the phagolysosomal DNAse, DNAseII and, together with Kate Fitzgerald, in mice that express gain-of-function mutations in STING. Both models recapitulate clinical manifestations of patients with the corresponding mutations, autoimmune hepatitis in patients with hypomorphic mutations in DNaseII and pulmonary inflammation in patients with GOF STING. Other interests include the role of FasL in the regulation of ocular disorders.