Min Ae Lee-Kirsch Group
Molecular genetics of autoimmune diseases
Our group focuses on the molecular mechanisms that underlie autoimmunity. Systemic lupus erythematosus is a prototypic autoimmune disease with a broad spectrum of clinical manifestations. It is characterized by loss of tolerance to nuclear antigens such as nucleic acids, formation of auto-antibodies and immune complexes that deposit in tissues and cause widespread inflammation. There is strong evidence for a central role of type I-interferons (IFN) in lupus pathogenesis. Type I-IFNs play a pivotal role in the first line of defense against viral infections. Type I-IFNs sensitize cells to apoptosis, enhance dendritic cell activation, and promote activation and differentiation of auto-reactive B cells. If inappropriately activated, type I-IFNs drive a positive feed-back loop that leads to breakdown of tolerance.
Mutations in intracellular nucleic acid degrading enzymes such as TREX1 cause lupus or lupus-associated syndromes. Nuclease deficiency is thought to result in the intracellular accumulation of nucleic acid species, which induce an antiviral type I-IFN response by triggering intracellular innate sensors. Combining genetics, cell biology, mass spectrometry and fluorescence imaging techniques our studies aim to dissect the pathogenic pathways that lead to the phenotypic expression of autoimmune disease.
Future Projects and Goals
- To identify genes causing monogenic and multifactorial autoimmune diseases in humans and to unravel their contribution to disease pathogenesis.
- To understand the role of nucleic acid metabolism in mechanisms of immune defense and tolerance.
- To translate basic science knowledge into clinically relevant concepts.
Methodological and Technical Expertise
- molecular and cell biology
- protein biochemistry/recombinant protein expression
- confocal microscopy
- flow cytometry
- genetic linkage/association analysis