About the Leifer Lab: The innate immune system is designed to protect us from microbial invasion; however not all microbes are harmful, and often it is best to avoid, or tailor, responses so that the immune system does not itself cause disease. Failure in regulation of immune responses leads to chronic inflammation, and autoimmunity. The overall theme of my research is to understand how innate immune receptors are regulated. This is important for human health because although most innate immune receptors detect unique molecular structures present on microbes and not in the host, a few detect highly conserved structures such as nucleic acids (DNA and RNA). Transmembrane receptors that detect DNA and RNA belong to a family of innate immune receptors called Toll-like receptors (TLRs).
TLR9 is the receptor for DNA and is our model system. We have shown that TLR9 and other nucleic acid sensing TLRs are unique because they are not expressed at the cell surface, that TLR9 traffics through the Golgi to reach endosomes, and have identified sequences in the cytoplasmic tail that regulate these events. Our most recent studies have identified a critical tyrosine that differentially regulates cytokine production, and have uncovered a unique endogenous negative regulatory form of TLR9. We believe that identification of these regulatory events will reveal proteins or pathways that are therapeutic targets for interfering with TLR9 function and will lead to new treatments for autoimmune diseases such as Systemic Lupus Erythematosus and Inflammatory Bowel Disease.