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Principal Investigator, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital
Associate Professor of Medicine, Harvard Medical School
Research Affiliate, Broad Institute of MIT and Harvard
The Means Laboratory conducts research in the field of immunology with an emphasis on the molecular and cellular mechanisms of inflammation and host defense. Our research to date has focused on the role that mammalian Toll-like receptors (TLR), Scavenger Receptors and TREM receptors play in the innate immune response to a myriad of danger molecules derived from foreign and self-host sources. We study these inflammatory pathways using biochemical (ELISA, Luminex), live cell imaging (confocal microscopy), and genetic (RNAi/CRISPR-Cas9, transgenic mice) approaches. Our recent studies have focused on identifying novel signaling pathways and sensors involved in regulating innate immune cell inflammatory responses to danger molecules. To aid these studies my laboratory maintains an active collaboration with the RNAi Consortium at the Broad Institute to generate and optimize RNAi libraries in a lentiviral vector that delivers shRNAs to a wide range of cell types, including dendritic cells. The design of a streamlined lentiviral vector has enabled us to produce very high-titer virus particles for each construct of the library in a high-throughput fashion, allowing us to carry out arrayed and genome-wide pooled assays. Our lab has used this lentiviral-based shRNA technology to discover that (1) scavenger receptors function as TLR co-receptors in the recognition of fungal pathogens (Means et al. JEM 2009), (2) synaptotagmin proteins regulate cell migration (Colvin et al. Nat Immunol. 2010), (3) the scavenger receptor SCARA1 mediates clearance of beta amyloid (Frankel et al. Nature Commun. 2013), (4) the scavenger receptor SCARF1 mediates clearance of apoptotic cells and prevents spontaneous lupus-like autoimmune disease (Ramirez-Ortiz et al. Nature Immunol. 2013), and (5) we recently discovered that the receptor TREML4 is an essential positive regulator of TLR7 signaling and promotes autoimmunity (Ramirez-Ortiz et al. Nature Immunol. 2015).
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