A5103036463- Viral Infections and Outbreaks Research
- Viral Infections and Vectors
- SARS-CoV-2 and COVID-19 Research
- Hepatitis B Virus Studies
- Radiopharmaceutical Chemistry and Applications
- COVID-19 Clinical Research Studies
- Head and Neck Cancer Studies
- Viral gastroenteritis research and epidemiology
- Lung Cancer Research Studies
- Medical Imaging Techniques and Applications
- Thyroid Cancer Diagnosis and Treatment
- Neuroendocrine Tumor Research Advances
- Animal Disease Management and Epidemiology
- Digestive system and related health
- Neuroblastoma Research and Treatments
- Mosquito-borne diseases and control
- Salivary Gland Tumors Diagnosis and Treatment
- Hematological disorders and diagnostics
- Viral Infections and Immunology Research
- Single-cell and spatial transcriptomics
- Vector-Borne Animal Diseases
- Immune Cell Function and Interaction
- interferon and immune responses
- Medical Imaging and Pathology Studies
- Genetic and phenotypic traits in livestock
The University of Texas Medical Branch at Galveston
2016-2024
Galveston College
2018-2024
Seqirus (United States)
2024
University of Virginia
2023
Oak Ridge Institute for Science and Education
2019
Oak Ridge Associated Universities
2019
All India Institute of Medical Sciences
2012-2018
DR. B.R.A. Institute Rotary Cancer Hospital
2014-2017
Institute of Medical Sciences
2017
Plum Island Animal Disease Center
2015
Most current Ebola virus (EBOV) vaccine candidates are based on viral vectors, some of which cause side effects or require complex manufacturing. Modified mRNA vaccines easily produced, safe, and highly immunogenic. We developed 2 the EBOV envelope glycoprotein, differed by nature signal peptide for improved glycoprotein post-translational translocation. The mRNAs were formulated with lipid nanoparticles to facilitate delivery. Vaccination guinea pigs induced EBOV-specific IgG neutralizing...
ABSTRACT Ebola virus (EBOV) disease (EVD) results from an exacerbated immunological response that is highlighted by a burst in the production of inflammatory mediators known as “cytokine storm.” Previous reports have suggested nonspecific activation T lymphocytes may play central role this phenomenon. T-cell immunoglobulin and mucin domain-containing protein 1 (Tim-1) has recently been shown to interact with virion-associated phosphatidylserine promote infection. Here, we demonstrate Tim-1...
African swine fever (ASF) is a disease caused by large, structurally complex, double-stranded DNA virus, virus (ASFV). In domestic pigs, acute infection highly virulent ASF viruses causes hemorrhagic and death. Previous work has suggested that ASFV pathogenesis primarily mediated host cytokines produced infected monocytes macrophages. To better understand molecular mechanisms mediating immune evasion, we used transcriptome analysis to identify gene expression changes after in ex vivo Our...
Highlights•mAbs from filovirus human survivors tested for their ability to facilitate ADE•ADE is not restricted a particular epitope, neutralizing capacity, or subclass•Lower-affinity interactions still cause counteracts antibody-mediated protection and facilitates infectionSummarySome monoclonal antibodies (mAbs) recovered of infections can protect against infection. It currently unknown whether natural infection also induces some with the capacity antibody-dependent enhancement (ADE). A...
Insulin is known to be an important regulator of milk secretion in the lactating mammary gland. Here we examine role insulin signaling development pregnancy using a mouse with floxed receptor (IR) crossed expressing Cre specifically In glands these IR(fl/fl) Cre(+) mice, expression IR significantly diminished throughout development. Glands from mice had 50% fewer alveoli at midpregnancy; casein and lipid droplets were by 60 75%, respectively, indicating for both alveolar differentiation....
The 2013-2016 outbreak of Ebola virus (EBOV) in West Africa, which has seen intermittent reemergence since it was officially declared over February 2016, demonstrated the need for rapid development therapeutic intervention strategies. Indirect evidence suggested that EBOV infection shares several commonalities associated with onset bacterial sepsis, including a "cytokine storm." Eritoran, Toll-like receptor 4 (TLR4) antagonist, previously shown to result protection mice against lethal...
Abstract Protective immunity against COVID-19 likely depends on the production of SARS-CoV-2–specific plasma cells and memory B postinfection or postvaccination. Previous work has found that germinal center reactions are disrupted in severe COVID-19. This may adversely affect long-term reinfection. Consistent with an extrafollicular cell response, patients have elevated frequencies clonally expanded, class-switched, unmutated plasmablasts. However, it is unclear whether populations...
Ebola virus (EBOV) infections are characterized by a pronounced lymphopenia that is highly correlative with fatalities. However, the mechanisms leading to T-cell depletion remain largely unknown. Here, we demonstrate both viral mRNAs and antigens detectable in CD4+ T cells despite absence of productive infection. A protein phosphatase 1 inhibitor, 1E7-03, siRNA-mediated suppression were used de novo synthesis RNAs cells, respectively. Cell-to-cell fusion permissive Huh7 non-permissive Jurkat...
The mRNA-1273 vaccine is effective against SARS-CoV-2 and was granted emergency use authorization by the FDA. Clinical studies, however, cannot provide controlled response to infection complex immunological insight that are only possible with preclinical studies. Hamsters model reliably exhibits severe disease similar in hospitalized patients, making them pertinent for evaluation. We demonstrate prime or prime-boost administration of hamsters elicited robust neutralizing antibodies,...
Ebola virus (EBOV) genome and mRNAs contain long, structured regions that could hijack host RNA-binding proteins to facilitate infection. We performed RNA affinity chromatography coupled with mass spectrometry identify bind EBOV RNAs identified four high-confidence proviral factors, including Staufen1 (STAU1), which specifically binds both 3' 5' extracistronic of the genome. confirmed infection rate production infectious particles were significantly reduced in STAU1-depleted cells. STAU1 was...
The filoviruses Marburg virus (MARV) and Ebola (EBOV) cause hemorrhagic fever in humans nonhuman primates, with high case fatality rates. MARV VP30 is known to be phosphorylated interact nucleoprotein (NP), but its role regulation of viral transcription disputed. Here, we analyzed phosphorylation by mass spectrometry, which resulted identification multiple amino acids. Modeling the full-length three-dimensional structure mapping identified sites showed that all lie disordered regions, mostly...
HIV-1 viral protein R (Vpr) is a virion-associated gene product that profoundly affects T cell proliferation, induces apoptosis and can affect cytokine production in part through interfering with NF-kappa B-mediated transcription from host cells. Collectively, these effects support Vpr could influence immune activation vivo. However, this effect of has not been explored previously. Here we examined the expression an vivo model system on induction antigen-specific responses using DNA vaccine...
Profiling of RNA from mouse mammary epithelial cells (MECs) isolated on pregnancy day (P)14 and lactation (L)2 revealed that the majority differentially expressed microRNA declined precipitously between late lactation. The decline in miR-150, which exhibited greatest fold-decrease, was verified quantitatively qualitatively. To test hypothesis miR-150 is crucial for lactation, MEC-specific constitutive achieved by crossing ROSA26-lox-STOP-lox-miR-150 mice with WAP-driven Cre recombinase mice....
The lysosomal storage disease, canine fucosidosis, is caused by the absence of enzyme α-<i>L</i>-fucosidase with undegraded fucose-rich material in different organs. Canine fucosidosis a severe, progressive, fatal neurological disease which results death or euthanasia and only available animal model for this human disease. We analysed progressive neuropathology from birth to severe clinical related signs. At no vacuolation was observed brain; however, complex presence well...
Viral apoptotic mimicry, which is defined by exposure of phosphatidylserine (PtdSer) into the outer leaflet budding enveloped viruses, increases viral tropism, infectivity and promotes immune evasion. Here, we report that calcium (Ca2+)-dependent scramblase, transmembrane protein 16F (TMEM16F), responsible for incorporation PtdSer virion membranes during Ebola virus infection. Infection Huh7 cells with resulted in a pronounced increase plasma membrane-associated PtdSer, was demonstrated to...
ABSTRACT The mRNA-1273 vaccine was recently determined to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from interim Phase 3 results. Human studies, however, cannot provide the controlled response infection and complex immunological insight that are only possible with preclinical studies. Hamsters model reliably exhibit more SARS-CoV-2 disease similar hospitalized patients, making them pertinent for evaluation. We demonstrate prime or prime-boost...
Respiratory tract vaccination has an advantage of needle-free delivery and induction mucosal immune response in the portal SARS-CoV-2 entry. We utilized human parainfluenza virus type 3 vector to generate constructs expressing full spike (S) protein SARS-CoV-2, its S1 subunit, or receptor-binding domain, tested them hamsters as single-dose intranasal vaccines. The construct bearing full-length S induced high titers neutralizing antibodies specific domains critical functions. Robust memory T...
Mammary transcriptome analyses across the lactation cycle and transgenic animal studies have identified candidate genes for mammogenesis, lactogenesis involution; however, there is a lack of information on pathways that contribute to performance. Previously we shown significant differences in performance, mammary gland histology, gene expression profiles during [lactation day 9 (L9)] between CBA/CaH (CBA) superior performing QSi5 strains mice. In present study, compared these at midpregnancy...
Abstract Background Highly fecund mouse strains provide an ideal model to understand the factors affecting maternal performance. The QSi5 inbred strain of mice was selected for high fecundity and low inter-litter interval, is very successful at weaning large numbers offspring when compared other strains. Results Post-natal pup weight gain used estimate mammary gland output compare performance CBA mice. Cumulative litter weights individual significantly higher throughout first eight days...
The outer leaflet of the viral membrane Ebola virus (EBOV) virions is enriched with phosphatidylserine (PtdSer), which thought to play a central role in tropism, entry, and virus-associated immune evasion. We investigated effects inhibiting synthesis and/or export PtdSer cell surface infected cells on infectivity. Knockdown both synthase enzymes, PTDSS1 PTDSS2, effectively decreased production. Decreased expression resulted an accumulation at plasma adjacent intracellular organelles,...
Comparative immune response profiling is important for selecting next-generation vaccines. We comprehensively evaluated the antibody responses from a panel of nine respiratory vaccines against Ebola virus (EBOV) derived human and avian paramyxoviruses expressing EBOV glycoprotein (GP). Most were protective in guinea pigs but yielded repertoires that differed proportion targeting key antigenic regions, avidity, neutralizing specificities, linear epitope preferences. Competition studies with...