C. A. Schiffer

Direct delivery of stabilized Cas-embedded base editors achieves efficient and accurate editing of clinically relevant targets

This study develops stabilized Cas-embedded base editors (sCE_CBEs) that enable efficient and accurate C-to-T editing with minimal off-target effects in hematopoietic stem and progenitor cells.

Addressing the dNTP bottleneck restricting prime editing activity

This study identifies mutations to improve prime editing efficiency in low-dNTP environments by enhancing MMLV-reverse transcriptase and reducing SAMHD1 activity.

Contributions of hyperactive mutations in Mpro from SARS-CoV-2 to drug resistance

This study identifies hyperactive mutations in SARS-CoV-2 Mpro that increase enzyme activity and contribute to drug resistance, finding them more prevalent than binding-reducing mutations.

FruitFire: a luciferase based on a fruit fly metabolic enzyme

The paper describes the creation of an artificial luciferase, FruitFire, by modifying a fruit fly enzyme to enable in vivo bioluminescence imaging.

Crystal Structures of Inhibitor-Bound Main Protease from Delta- and Gamma-Coronaviruses

The paper determines inhibitor-bound crystal structures of main proteases from delta and gamma coronaviruses to inform structure-based inhibitor design.

Structure of the catalytically active APOBEC3G bound to a DNA oligonucleotide inhibitor reveals tetrahedral geometry of the transition state

The paper determines the structure of APOBEC3G bound to a DNA inhibitor, revealing the transition state geometry and providing insights for inhibitor design.

Bacterial pattern recognition in C. elegans by a nuclear hormone receptor

The paper identifies NHR-86/HNF4 as a bacterial pattern recognition receptor in C. elegans that detects phenazine-1-carboxamide from Pseudomonas aeruginosa to trigger an anti-pathogen response.

Selection of HIV-1 for Resistance to Fifth Generation Protease Inhibitors Reveals Two Independent Pathways to High-Level Resistance

This study identifies two independent resistance pathways to fifth-generation protease inhibitors in HIV-1 by analyzing mutations under high drug concentrations.

Deciphering the Molecular Mechanism of HCV Protease Inhibitor Fluorination as a General Approach to Avoid Drug Resistance

The paper investigates how fluorination of HCV protease inhibitors improves resistance to the D168A variant by enabling alternate binding conformations through co-crystal structure analysis.

Defining the Substrate Envelope of SARS-CoV-2 Main Protease to Predict and Avoid Drug Resistance

This study defines the substrate envelope of SARS-CoV-2 main protease using cocrystal structures to identify vulnerable sites that may lead to drug resistance.

Quantitative Structural Analysis of Influenza Virus by Cryo-electron Tomography and Convolutional Neural Networks

This paper develops a cryoET processing pipeline using CNNs to characterize the morphology and structure of influenza viruses, improving analysis throughput and enabling subtomogram averaging of glycoproteins.

Deciphering complex mechanisms of resistance and loss of potency through coupled molecular dynamics and machine learning.

This paper uses molecular dynamics and machine learning to identify conserved dynamic mechanisms of drug resistance in HIV-1 protease variants.

IgA MAb blocks SARS-CoV-2 Spike-ACE2 interaction providing mucosal immunity

This study identifies an IgA monoclonal antibody that blocks SARS-CoV-2 Spike-ACE2 interaction and provides mucosal immunity.

CryoEM Structure of CtBP2 Confirms Tetrameric Architecture

The paper presents cryoEM structures of CtBP2 confirming its tetrameric architecture in the presence of NADH and shows that tetramer formation is essential for transcriptional activity and cell migration.

Molecular and structural mechanism of pan-genotypic HCV NS3/4A protease inhibition by glecaprevir

This study determines the crystal structures of HCV NS3/4A protease from multiple genotypes bound to glecaprevir, revealing molecular mechanisms of pan-genotypic inhibition and resistance-associated substitutions.

Constrained mutational sampling of amino acids in HIV-1 protease evolution

The paper investigates HIV-1 protease evolution by comparing experimental fitness landscapes with sequenced isolate data, showing mutational sampling influences multiple mutations.

HIV-1 Protease Uses Bi-Specific S2/S2’ Subsites To Optimize Cleavage of Two Classes of Target Sites

This study shows HIV-1 protease uses bi-specific S2/S2’ subsites to cleave two classes of target sites, with distinct interactions based on the presence or absence of a P1 proline.

Structural analysis of the active site and DNA binding of human cytidine deaminase APOBEC3B

This study identifies the structural basis for APOBEC3B's lower catalytic activity and DNA binding through molecular modeling and mutational analysis.

Substrate sequence selectivity of APOBEC3A implicates intra-DNA interactions

This study identifies the APOBEC3A ssDNA binding motif and shows that substrate affinity is influenced by DNA structure, not just sequence, leading to a new model for its sequence preference.