A5032778910- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- Bacteriophages and microbial interactions
- RNA Research and Splicing
- Genomics and Chromatin Dynamics
- Advanced biosensing and bioanalysis techniques
- Cytomegalovirus and herpesvirus research
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Virus-based gene therapy research
- RNA Interference and Gene Delivery
- Nuclear Structure and Function
- CRISPR and Genetic Engineering
- Quantum Dots Synthesis And Properties
- Immune Cell Function and Interaction
- Protein purification and stability
- Ion-surface interactions and analysis
- Numerical Methods and Algorithms
- Crystallization and Solubility Studies
- Chalcogenide Semiconductor Thin Films
- Signaling Pathways in Disease
- Statistical and Computational Modeling
- Cancer Mechanisms and Therapy
- Selenium in Biological Systems
- Biochemical and Structural Characterization
Dana-Farber Cancer Institute
2017-2025
Harvard University
2019-2025
University of Alabama at Birmingham
2011-2017
Abstract The host cell factor cyclophilin A (CypA) interacts directly with the HIV-1 capsid and regulates viral infectivity. Although crystal structure of CypA in complex N-terminal domain protein (CA) has been known for nearly two decades, how modulates infectivity remains unclear. We determined cryoEM assembled at 8-Å resolution. exhibits a distinct CypA-binding pattern which selectively bridges CA hexamers along direction highest curvature. EM-guided all-atom molecular dynamics...
Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules their complexes, reporting on size shape in free solution. The purpose this multi-laboratory study was establish the precision accuracy basic data dimensions AUC validate previously proposed calibration techniques. Three kits cell assemblies containing radial temperature tools bovine serum albumin (BSA) reference sample were...
Integration is the defining step of retroviral life cycle and underlies inability to cure HIV/AIDS through use intensified antiviral therapy. The reservoir latent, replication-competent proviruses that forms early during HIV infection reseeds viremia when patients discontinue medication. research accordingly focused on factors guide provirus formation associated chromatin environments regulate transcriptional reactivation, studies orthologous infectious agents such as nonprimate lentiviruses...
Abstract Non-suppressible HIV-1 viremia (NSV) is defined as persistent low-level on antiretroviral therapy (ART) without evidence of ART non-adherence or significant drug resistance. Unraveling the mechanisms behind NSV would broaden our understanding persistence. Here we analyzed plasma virus sequences in eight ART-treated individuals with (88% male) and show that they are composed large clones viral evolution over time those longitudinal samples. We proviruses match RNA ‘producer...
Abstract HIV-1 integration favors nuclear speckle (NS)-proximal chromatin and viral infection induces the formation of capsid-dependent CPSF6 condensates that colocalize with speckles (NSs). Although displays liquid-liquid phase separation (LLPS) activity in vitro, contributions its different intrinsically disordered regions, which includes a central prion-like domain (PrLD) capsid binding FG motif C-terminal mixed-charge (MCD), to LLPS remain unclear. Herein, we determined PrLD MCD both...
The phosphoprotein (P) is virally encoded by the Rhabdoviridae and Paramyxoviridae in order Mononegavirales. P a self-associated oligomer forms complexes with large viral polymerase protein (L), nucleocapsid (N), assembled nucleocapsid. from different viruses has shown structural diversities even though their essential functions are same. We systematically mapped domains mumps virus (MuV) investigated interactions nucleocapsid-like particles (NLPs). Similar to other proteins, MuV contains...
RATIONALE Charge state resolution is required to determine the masses of ions in electrospray mass spectrometry, a feat which becomes increasingly difficult as increases. detection spectrometry (CDMS) circumvents this limitation by simultaneously measuring charge and m/z individual ions. In work, we have used CDMS number scaffolding proteins associated with bacteriophage P22 procapsids. METHODS procapsids containing native cargo protein were assembled E. coli purified via differential...
Cleavage factor I mammalian (CFIm) complex, composed of cleavage and polyadenylation specificity 5 (CPSF5) serine/arginine-like protein CPSF6, regulates alternative (APA). Loss CFIm function results in proximal site usage, shortening mRNA 3′ untranslated regions (UTRs). Although CPSF6 plays additional roles human disease, its nuclear translocation mechanism remains unresolved. Two β-karyopherins, transportin (TNPO) 1 TNPO3, can bind vitro, we demonstrate here that while the TNPO1 binding is...
HIV-1 integrase and capsid proteins interact with host to direct preintegration complexes active transcription units within gene-dense regions of chromosomes for viral DNA integration. Analyses spatially-derived genomic coordinates, such as nuclear speckle-associated domains, lamina-associated super enhancers, Spatial Position Inference the Nuclear (SPIN) genome states, have further informed mechanisms integration targeting. Critically, however, these different types coordinates not been...
The early stages of HIV-1 infection include the trafficking viral core into nucleus infected cells. However, much remains to be understood about how accomplishes nuclear import and consequences pathways utilized on events. host factor cleavage polyadenylation specificity 6 (CPSF6) assists localization post-entry integration targeting. Here, we used a CPSF6 truncation mutant lacking functional signal (NLS), CPSF6-358, appended heterologous NLSs rescue localization. We show that some, but not...
Engineered virus-like particles (VLP) are attractive for fabricating nanostructured materials applications in diverse areas such as catalysis, drug delivery, biomedicine, composites, etc. Basic understanding of the interaction between inorganic guest and biomolecular host is thus important controlled synthesis nanoparticles inside VLP rational assembly ordered VLP-based hierarchical nanostructures. We have investigated detail formation mechanism growth kinetics semiconducting nanocrystals...
A multimer of retroviral integrase (IN) synapses viral DNA ends within a stable intasome nucleoprotein complex for integration into host cell genome. Reconstitution the from maedi-visna virus (MVV), an ovine lentivirus, revealed large assembly containing sixteen IN subunits1. Herein, we report cryo-EM structures lentiviral prior to engagement target and following strand transfer, refined at 3.4 3.5 Å resolution, respectively. The elucidate details protein-protein protein-DNA interfaces...
The initiation and elongation stages of translation are directed by codon–anticodon interactions. In contrast, a release factor protein mediates stop codon recognition prior to polypeptide chain release. Previous studies have identified specific regions eukaryotic one (eRF1) that important for decoding each codon. cavity model suggests three binding pockets/cavities located on the surface eRF1's domain key elements in recognition. Thus, predicts amino acid changes or near these cavities...
Biological organisms have evolved tremendous control over the synthesis of inorganic materials in aqueous solutions at standard conditions. Such material properties is difficult to achieve with current strategies. Biotemplated has been demonstrated be efficient facilitating formation various species. In this study, we employ a protein cage-based system synthesize photoactive TiO2 nanoparticles less than 10 nm diameter. We also demonstrate phase material, ability both anatase and rutile using...
HIV-1 integration favors recurrent gene (RIG) targets and genic proviruses can confer cell survival in vivo. However, the relationship between initial RIG integrants how these evolve patients over time are unknown. To address shortcomings, we built phenomenological models of random silico, which were used to identify 3718 RIGs as well 2150 avoided genes from 1.7 million sites across 10 vitro datasets. Despite comprising only 13% human genes, they harbored 70% integrations patient-derived...
Plasmonic photocatalytic nanostructures have been fabricated under mild conditions (room temperature aqueous solution) using genetically engineered bacteriophage P22 virus-like particles (VLP) as a nano-platform. The photodegradation of methylene blue by CdS photocatalyst confined inside VLP can be significantly enhanced the controlled deposition gold nanoparticles on outer shell VLP-CdS.
Purified retroviral Gag proteins can assemble in vitro to form immature virus-like particles (VLPs). By cryoelectron tomography, Rous sarcoma virus VLPs show an organized hexameric lattice consisting chiefly of the capsid (CA) domain, with periodic stalk-like densities below lattice. We hypothesize that structure represented by these is formed amino acid residues immediately downstream folded CA, namely, short spacer peptide SP, along a dozen flanking residues. These 24 comprise SP assembly...
The early stages of HIV-1 infection include the trafficking viral core into nucleus infected cells. However, much remains to be understood about how accomplishes nuclear import and consequences pathways utilized on events. host factor cleavage polyadenylation specificity 6 (CPSF6) assists localization post-entry integration targeting. Here, we used a CPSF6 truncation mutant lacking functional signal (NLS), CPSF6-358, appended heterologous NLSs rescue localization. We show that some, but not...