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Etemad, Behzad

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Etemad

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Behzad

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Etemad, Behzad

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2012 - 201922020 - 20211

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Author's Publications: search.filters.isAuthorOfPublication.df9cb3b7-be7c-4b0a-80f5-c024677d09af

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    Detection and manipulation of live antigen-expressing cells using conditionally stable nanobodies
    (eLife Sciences Publications, Ltd, 2016) Tang, Jonathan CY; Drokhlyansky, Eugene; Etemad, Behzad; Rudolph, Stephanie; Guo, Ella; Wang, Sui; Ellis, Emily G; Li, Jonathan; Cepko, Constance
    The ability to detect and/or manipulate specific cell populations based upon the presence of intracellular protein epitopes would enable many types of studies and applications. Protein binders such as nanobodies (Nbs) can target untagged proteins (antigens) in the intracellular environment. However, genetically expressed protein binders are stable regardless of antigen expression, complicating their use for applications that require cell-specificity. Here, we created a conditional system in which the stability of an Nb depends upon an antigen of interest. We identified Nb framework mutations that can be used to rapidly create destabilized Nbs. Fusion of destabilized Nbs to various proteins enabled applications in living cells, such as optogenetic control of neural activity in specific cell types in the mouse brain, and detection of HIV-infected human cells by flow cytometry. These approaches are generalizable to other protein binders, and enable the rapid generation of single-polypeptide sensors and effectors active in cells expressing specific intracellular epitopes. DOI: http://dx.doi.org/10.7554/eLife.15312.001
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    Envelopes Found Early After Acquisition Compared to Those in the Chronically Infected Partner Do Not Have Enhanced Alpha4 Beta7 Binding or Utilization
    (BioMed Central, 2012) Etemad, Behzad; Redd, A; Serwadda, D; Lutalo, T; Reynolds, S; Gray, R; Quinn, T; Sagar, Manish
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    Two Mutations in the SARS-CoV-2 Spike Protein and RNA Polymerase Complex Are Associated With COVID-19 Mortality Risk
    (2021) Hahn, Georg; Wu, Chloe M.; Lee, Sanghun; Hecker, Julian; Lutz, Sharon; Haneuse, Sebastien; Qiao, Dandi; Demeo, Dawn; Tanzi, Rudolph; Choudhary, Manish; Etemad, Behzad; Mohammadi, Abbas; Esmaeilzadeh, Elmira; Cho, Michael M.; Li, Jonathan; Randolph, Adrienne; Laird, Nan; Weiss, Scott; Silverman, Edwin; Ribbeck, Katharina; Lange, Christoph
    SARS-CoV-2 mortality has been extensively studied in relation to host susceptibility. How sequence variations in the SARS-CoV-2 genome affect pathogenicity is poorly understood. Association between whole-genome sequencing (WGS) of the virus and death in patients with SARS-CoV-2 is one potential method of early identification of highly pathogenic strains to target for containment. We analyzed 7,548 single stranded RNA-genomes of SARS-CoV-2 patients in the GISAID database and associated variants with mortality using a logistic regression. In total, evaluating 29,891 sequenced loci of the viral genome for association with patient/host mortality, two loci, at 12,053bp and 25,088bp, achieved genome-wide significance (p-values of 4.09e-09 and 4.41e-23, respectively). Mutations at 25,088bp occur in the S2 subunit of the SARS-CoV-2 spike protein, which plays a key role in viral entry of target host cells. Additionally, mutations at 12,053bp are within the ORF1ab gene, in a region encoding for the protein nsp7, which is necessary to form the RNA polymerase complex responsible for viral replication and transcription. Both mutations alter amino acid coding sequences, potentially imposing structural changes that could enhance viral infectivity and symptom severity, and may be important to consider as targets for therapeutic development. Identification of these highly significant associations, unlikely to occur by chance, may assist with COVID-19 early containment of strains that are potentially highly pathogenic.