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Research in the Steinhauer laboratory is focused on the structure and functions of the influenza virus hemagglutinin glycoprotein (HA). HA is the principal target of neutralizing antibody responses, and therefore, the viral component of primary concern with regard to vaccine design. It also supplies two crucial functions during the process of virus entry. It binds to sialic acid-containing glycan receptor molecules on cell surfaces, and following internalization, it mediates fusion of viral and endosomal membranes to transfer the viral genome to the cell cytoplasm. Each of these processes constitutes a potential target for anti-viral intervention, and the deep understanding of high resolution HA structures, the availability of genetic manipulation systems for influenza and the wealth of resources and reagents they have accumulated over the years places them in optimal position to make significant progress toward this goal over the coming years. The lab is designing high affinity or multivalent compounds to block viral HA interactions with host receptors to provide anti-viral countermeasures. With regard to membrane fusion, current work using genetic systems and functional assays has allowed for the identification of specific amino acid residues that appear to provide the initial triggers for the molecular rearrangements that drive the fusion process during virus entry.
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