A5013629060- Influenza Virus Research Studies
- Respiratory viral infections research
- HIV Research and Treatment
- Immune Response and Inflammation
- vaccines and immunoinformatics approaches
- RNA Research and Splicing
- Immunotherapy and Immune Responses
- Viral gastroenteritis research and epidemiology
- Monoclonal and Polyclonal Antibodies Research
- Hepatitis C virus research
- Virus-based gene therapy research
- Cytomegalovirus and herpesvirus research
- Heat shock proteins research
- Immune Cell Function and Interaction
- SARS-CoV-2 and COVID-19 Research
- ATP Synthase and ATPases Research
- Computational Drug Discovery Methods
- RNA Interference and Gene Delivery
- Bacterial Infections and Vaccines
- Amoebic Infections and Treatments
- Genomics and Chromatin Dynamics
- Escherichia coli research studies
- RNA regulation and disease
- Viral Infectious Diseases and Gene Expression in Insects
- Hepatitis B Virus Studies
Seqirus (United States)
2016-2023
China Medical University
2019
Novartis (United States)
2012-2018
Novartis (Switzerland)
2013-2015
Global Vaccines (United States)
2014
Computational Physics (United States)
2008
Pearl River Community College
2008
Rutgers, The State University of New Jersey
1998-2000
RNA polymerase II nascent transcripts are capped during pausing before elongation. Here we report that hSPT5, the human homolog of yeast elongation factor SPT5, interacts directly with capping enzyme. hSPT5 stimulated enzyme guanylylation and mRNA by severalfold. Although 5'-triphosphatase activity was unaffected, binding to this domain in full-length is likely involved stimulation, as did not increase guanylyltransferase fragment. Consistent binding, TFIIH-phosphorylated CTD guanylylation,...
Synthesis of viral genes from sequence information allows rapid generation influenza vaccine viruses, facilitating responses to pandemics.
Heat shock protein 90 (Hsp90) is a molecular chaperone that responsible for activating many signaling proteins and promising target in tumor biology. We have identified small-molecule benzisoxazole derivatives as Hsp90 inhibitors. Crystallographic studies show these compounds bind the ATP binding pocket interacting with Asp93. Structure based optimization led to identification of potent analogues, such 13, good biochemical profiles.
Mammalian capping enzymes are bifunctional proteins with both RNA 5′-triphosphatase and guanylyltransferase activities. The N-terminal 237-aa triphosphatase domain contains (I/V)HCXXGXXR(S/T)G, a sequence corresponding to the conserved active-site motif in protein tyrosine phosphatases (PTPs). Analysis of point mutants mouse identified Cys Arg residues an upstream Asp as required for activity. Like PTPs, this enzyme was inhibited by iodoacetate VO 4 3− independent Mg 2+ , providing...
ABSTRACT Human cytomegalovirus (HCMV) causes significant disease worldwide. Multiple HCMV vaccines have been tested in man but only partial protection has achieved. The gH/gL/UL128/UL130/UL131A complex (Pentamer) is the main target of neutralizing antibodies seropositive individuals and raises high titers small animals non‐human primates (NHP). Thus, Pentamer a promising candidate for an effective vaccine. Development Pentamer‐based subunit vaccine requires expression amounts functional...
The spike (S) protein of SARS-CoV-2 plays a crucial role in cell entry, and the nucleocapsid (N) is highly conserved among human coronavirus homologs. For potentially broad effectiveness against both original virus emerging variants, we developed Alphavirus-based self-amplifying mRNA (sa-mRNA) vaccines: an sa-mRNA S encoding full-length stabilized prefusion conformation S-N co-expressing N proteins for virus. We show that these vaccines raised potent neutralizing antibody responses mice not...
The RV144 Phase III clinical trial with ALVAC-HIV prime and AIDSVAX B/E subtypes CRF01_AE (A244) B (MN) gp120 boost vaccine regime in Thailand provided a foundation for the future development of improved strategies that may afford protection against human immunodeficiency virus type 1 (HIV-1). Results from this showed immune responses directed specific regions V1V2 viral envelope (Env) glycoprotein HIV-1, were inversely correlated to risk HIV-1 infection. Due low production proteins CHO...
We screened a human cDNA library for proteins that bind mRNA cap methyltransferase (MT) and isolated nuclear transporter importin-α (Impα). This direct association was confirmed by glutathione S -transferase (GST) pulldown, coimmunoprecipitation, colocalization. In gel shift assays, MT selectively bound RNA containing 5′-terminal GpppG, binding inhibited GpppG not m 7 GpppC. Impα markedly enhanced to GpppG-RNA stimulated activity. MT/RNA/Impα complexes were dissociated importin-β, which also...
Avian influenza viruses, such as A(H5N1) and A(H7N9), are primary public health concerns due to their pandemic potential. Influenza vaccines represent the most effective response this threat especially with timely provision. The current timelines require a substantial period for strain-specific reference antigen sera preparation use single-radial immunodiffusion (SRID), accepted vaccine potency assay. To address time lag, isotope dilution mass spectrometry (IDMS) method was developed...
Currently licensed influenza vaccines focus immune responses on viral hemagglutinin (HA), while the other major surface glycoprotein neuraminidase (NA) is not tightly controlled in inactivated vaccine formulations despite evidence that anti-NA antibodies reduce clinical disease. We utilized a bicistronic self-amplifying mRNA (sa-mRNA) platform encoding both HA and NA from four seasonal strains, creating quadrivalent vaccine. sa-mRNA an component induced production of NA-inhibiting CD4+...
Background Development of an effective vaccine against HIV-1 is challenging due to various viral evolutionary mechanisms evade human immune system. The partial efficacy the recent RV144 trial in Thailand provides hope for improvements regimens higher efficacy. A Phase IIb proof-of-concept clinical Republic South Africa (RSA) planned confirm and extend results with strategy poxvirus vector prime plus envelope protein boost.
Cyclic nucleotide phosphodiesterases (PDEs) play critical roles in maintaining the cellular concentration cGMP and cAMP. These key secondary messengers modify activation of cyclic dependent protein kinases that phosphorylate various substrates including ion channels transcription factors to regulate a myriad physiological processes. PDE4 is cAMP specific phosphodiesterase which has been suggested role regulation PKA/CREB pathway. The pathway impacts wide range responses, those involved...