Selected Publications

Academic Article

Year Title Altmetric
2021 Defining the influence of the a12.2 subunit on transcription elongation and termination by rna polymerase i in vivoGenes.  12. 2021
2021 Consequences of phosphorylation in a mononegavirales polymerase-cofactor systemJournal of Virology.  95. 2021
2021 Structure of nonstructural protein 1 from SARS-CoV-2Journal of Virology.  95. 2021
2020 Structure of nonstructural protein 1 from SARS-CoV-2. 2020
2020 Influenza-Induced Oxidative Stress Sensitizes Lung Cells to Bacterial-Toxin-Mediated NecroptosisCell Reports.  32. 2020
2020 The influenza NS1 protein modulates RIG-I activation via a strain-specific direct interaction with the second CARD of RIG-IJournal of Biological Chemistry.  295:1153-1164. 2020
2020 The connector domain of vesicular stomatitis virus large protein interacts with the viral phosphoproteinJournal of Virology.  94. 2020
2018 NETSeq reveals heterogeneous nucleotide incorporation by RNA polymerase 2018
2018 Structural analyses reveal the mechanism of inhibition of influenza virus NS1 by two antiviral compoundsJournal of Biological Chemistry.  293:14659-14668. 2018
2017 Native State Volume Fluctuations in Proteins as a Mechanism for Dynamic AllosteryJournal of the American Chemical Society.  139:3599-3602. 2017
2016 The AUDANA algorithm for automated protein 3D structure determination from NMR NOE dataJournal of Biomolecular NMR.  65:51-57. 2016
2015 Structural Basis for a Novel Interaction between the NS1 Protein Derived from the 1918 Influenza Virus and RIG-IFolding & design.  23:2001-2010. 2015
2014 Monitoring side-chain dynamics of proteins using 2H relaxationMethods in Molecular Biology.  1084:3-27. 2014
2014 Monitoring side-chain dynamics of proteins using2H relaxationMethods in Molecular Biology.  1084:3-27. 2014
2012 Structure and dynamics of the G121V Dihydrofolate reductase mutant: Lessons from a transition-state inhibitor complexPLoS One.  7. 2012
2011 Phosphorylation of a PDZ domain extension modulates binding affinity and interdomain interactions in postsynaptic density-95 (PSD-95) protein, a membrane-associated guanylate kinase (MAGUK).Journal of Biological Chemistry.  286:41776-41785. 2011
2009 Hidden dynamic allostery in a PDZ domain 2009
2005 Genetic analysis of the SARS-coronavirus spike glycoprotein functional domains involved in cell-surface expression and cell-to-cell fusion.Virology.  341:215-230. 2005

Research Overview

  • The influenza virus is a serious public health concern causing significant mortality and morbidity worldwide. The annual impact of which is largely determined by each strain’s ability to efficiently be transmitted from one host to another, or transmissibility, and the severity of the disease state caused by the virus, or virulence. While the interactions between viral and host proteins that determine transmissibility have been extensively studied, our understanding of the strain specific interactions that underlie virulence is extremely limited. One protein that facilitates viral evasion of the host immune response, and thus plays a critical role in modulating virulence, is the non-structural protein 1 (NS1). Not only does its absence attenuate influenza infection, certain variants also dramatically enhance virulence. NS1 is also considered to be a high valued target for the development of novel antivirals against influenza infection. Although many cellular proteins that interact with NS1 have been identified, a thorough structural and biophysical analysis of the strain dependent nature of these interactions is lacking. The knowledge gained by answering these questions will not only provide structural and biophysical insight into strain specific interactions that enhance virulence, but it will also guide the development of novel antivirals against influenza infection.

    The overall goal of my lab is to structurally and biochemically characterize the strain dependence of NS1 function through analysis of naturally occurring mutations in NS1. The rationale that underlies our research is that elucidating structure-function relationships between NS1 and its cellular interaction partners will provide critical insight into how influenza is able to evade the host immune response. To determine the strain dependent aspects of NS1 function, we will utilize a number of biophysical methods designed to interrogate the interaction between NS1 and host cell proteins. The primary method for determining and characterizing the interaction between NS1 and host proteins will be biomolecular nuclear magnetic resonance (NMR). For example, we will use an NMR technique known as chemical shift perturbation analysis to map intermolecular interface between NS1 and host cell proteins. Analysis of each interaction will include NS1 proteins derived from multiple strains of influenza to determine their dependence on strain. In addition, using multiple strains will identify naturally occurring mutations that are critical to the interactions being studied. Ultimately, this information will allow us to formulate further experiments using mutant recombinant influenza viruses to determine each naturally occurring mutation’s role in replication, the innate immune response, and pathogenicity.
  • Education And Training

  • Doctor of Philosophy in Veterinary Sciences / Veterinary Clinical Sciences, Louisiana State University System : Baton Rouge 2005
  • Full Name

  • Chad Petit