A5024531147- PARP inhibition in cancer therapy
- Calcium signaling and nucleotide metabolism
- Toxin Mechanisms and Immunotoxins
- Bacteriophages and microbial interactions
- Glycosylation and Glycoproteins Research
- Plant Virus Research Studies
- Escherichia coli research studies
- Mosquito-borne diseases and control
- Advancements in Semiconductor Devices and Circuit Design
- Biosimilars and Bioanalytical Methods
- RNA modifications and cancer
- Cancer Research and Treatments
- RNA Interference and Gene Delivery
- Soviet and Russian History
- Pediatric health and respiratory diseases
- Viral Infections and Vectors
- Respiratory viral infections research
- Ionosphere and magnetosphere dynamics
- Pancreatic function and diabetes
- Oral microbiology and periodontitis research
- RNA and protein synthesis mechanisms
- Enzyme Structure and Function
- Indigenous Studies and Ecology
- Salivary Gland Disorders and Functions
- Viral Infections and Outbreaks Research
Massachusetts Institute of Technology
2022-2023
Johns Hopkins University
2016-2021
University of Tartu
2018
Planetary Science Institute
2008
University of California, Los Angeles
2008
Significance Viral outbreaks can be sudden and result in devastating social economic consequences. Chikungunya virus (CHIKV) of rash, arthritis, neurologic disease have occurred Africa, Asia, Europe, the Americas. There are no licensed vaccines to prevent or drugs treat CHIKV infection, mechanisms generation poorly understood. Here, we identify a macrodomain-containing protein with enzymatic ADP-ribosylhydrolase activity that is critical for virulence mammals define substrate specificity...
Alphaviruses are plus-strand RNA viruses that cause encephalitis, rash, and arthritis. The nonstructural protein (nsP) precursor polyprotein is translated from genomic processed into four nsPs. nsP3 has a highly conserved macrodomain (MD) binds ADP-ribose (ADPr), which can be conjugated to as posttranslational modification involving transfer of ADPr NAD+ by poly polymerases (PARPs). nsP3MD also removes mono ADP-ribosylated (MARylated) substrates. To determine aspects alphavirus replication...
ADP ‐ribosylation is a conserved post‐translational protein modification that plays role in all major cellular processes, particularly DNA repair, transcription, translation, stress response and cell death. Hence, dysregulation of linked to the physiopathology several human diseases including cancers, diabetes neurodegenerative disorders. Protein can be reversed by macrodomain‐containing proteins PARG , TARG 1, MacroD1 MacroD2, which hydrolyse ester bond known link ‐ribose as well...
Macrodomain (MD), a highly conserved protein fold present in subset of plus-strand RNA viruses, binds to and hydrolyzes ADP-ribose (ADPr) from ADP-ribosylated proteins. ADPr-binding by the alphavirus nonstructural 3 (nsP3) MD is necessary for initiation virus replication neural cells, whereas hydrolase activity facilitates complex amplification. To determine importance these activities pathogenesis encephalomyelitis, mutations were introduced into nsP3 Sindbis (SINV), effects on ADPr binding...
Soluble human lectins are critical components of innate immunity. Genetic models suggest that influence host-resident microbiota, but their specificity for commensal and mutualist species is understudied. Elucidating lectins’ roles in regulating microbiota requires an understanding which microbial they bind within native communities. To profile lectin recognition, we developed Lectin-Seq. We apply Lectin-Seq to fecal using the soluble mannose-binding (MBL) intelectin-1 (hItln1). Although...
The oral microbiome is critical to human health and disease, yet the role that host salivary proteins play in maintaining unclear. A highly expressed gene glands encodes lectin zymogen granule protein 16 homolog B (ZG16B). Despite abundance of this protein, its interaction partners are unknown. ZG16B possesses a fold, but whether it binds carbohydrates We postulated would bind microbial glycans mediate recognition microbes. To end, we developed glycan analysis probe (mGAP) strategy based on...
Abstract ADP-ribosylation is a post-translational modification that occurs on chemically diverse amino acids, including aspartate, glutamate, lysine, arginine, serine and cysteine proteins mediated by ADP-ribosyltransferases, subset commonly known as poly(ADP-ribose) polymerases. ADP-ribose can be conjugated to singly monomer or in polymeric chains poly(ADP-ribose). While reversed ADP-ribosylhydrolases, this protein also processed phosphoribosylation enzymes possessing phosphodiesterase...
The arrival of high‐speed solar wind streams (HSSs) at the Earth's magnetopause drives particle and wave phenomena that are distinct from caused by other structures. Although HSS events do not generally produce a particularly strong ring current (the ions electrons drifting around Earth), they storm levels magnetospheric (enhanced convection, heating, precipitation, relativistic electron energization, so forth) can persist for an extended time period (e.g., many days). These contrast with...
Significance Severe coronavirus (CoV) infections have been responsible for hundreds of deaths. Since the emergence severely pathogenic CoVs, namely severe acute respiratory syndrome (SARS) virus in 2003, Middle East (MERS) 2012, and SARS-CoV-2 2019, no licensed vaccine or effective antiviral treatment has developed. Bats are reservoir hosts many human viruses, including SARS MERS. The protein relationship between betacoronaviruses their bat-specific ancestors is still unknown. This work...
ADP-ribosylation refers to the post-translational modification of protein substrates with monomers or polymers small molecule ADP-ribose. is enzymatically regulated and plays roles in cellular processes including DNA repair, nucleic acid metabolism, cell death, stress responses, antiviral immunity. Recent advances field have led development proteomics approaches enrich identify endogenous ADP-ribosylated peptides by liquid chromatography tandem mass spectrometry (LC-MS/MS). A number these...
ABSTRACT Macrodomains are a class of conserved ADP-ribosylhydrolases expressed by viruses pandemic concern, including coronaviruses and alphaviruses. Viral macrodomains critical for replication virus-induced pathogenesis; therefore, these enzymes promising target antiviral therapy. However, no potent or selective viral macrodomain inhibitors currently exist, in part due to the lack high-throughput assay this enzymes. Here, we developed ADP-ribosylhydrolase using SARS-CoV-2 Mac1. We performed...
SUMMARY ADP-ribosylation is a highly dynamic and fully reversible post-translational modification performed by poly(ADP-ribose) polymerases (PARPs) that modulates protein function, abundance, localization turnover. Here we show influenza A virus infection causes rapid dramatic upregulation of global inhibits viral replication. Mass spectrometry defined for the first time ADP-ribosylome during infection, creating an infection-specific profile with almost 4,300 sites on ∼1,080 host proteins,...
Abstract During nonhomologous end joining of DNA follow double-stranded breaks, one common signaling response is the adenosine diphosphate ribosylation (ADP-ribosylation) recruiter scaffold proteins. ADP-ribosylation a post-translational modification (PTM) that occurs on aspartate, glutamate, lysine, arginine and cysteine proteins mediated chiefly by polyadenosine ribose polymerases (PARP). Using NAD+ as its substrate, PARP transfers an ADP-ribose onto another protein, releasing nicotinamide...
Abstract Soluble human lectins are critical components of innate immunity. Genetic models suggest influence host-resident microbiota, but their specificity for commensal and mutualist species is understudied. Elucidating lectins’ roles in regulating microbiota requires understanding which microbial they bind within native communities. To profile lectin recognition, we developed Lectin-Seq. We apply Lectin-Seq to fecal using mannose-binding (MBL) intelectin-1 (hItln1). The interactomes MBL...