A5071238971- HIV Research and Treatment
- Folate and B Vitamins Research
- Power System Optimization and Stability
- Porphyrin Metabolism and Disorders
- HIV/AIDS drug development and treatment
- Trypanosoma species research and implications
- Research on Leishmaniasis Studies
- Power Systems Fault Detection
- Metabolism and Genetic Disorders
- Machine Fault Diagnosis Techniques
- Immune Cell Function and Interaction
- Power Quality and Harmonics
- Smart Grid Security and Resilience
- Immunotherapy and Immune Responses
- Monoclonal and Polyclonal Antibodies Research
- Power System Reliability and Maintenance
- Fault Detection and Control Systems
- Advanced Electrical Measurement Techniques
- Power Line Communications and Noise
- Biochemical and Molecular Research
- Ion channel regulation and function
- vaccines and immunoinformatics approaches
- PARP inhibition in cancer therapy
- T-cell and B-cell Immunology
- Smart Grid Energy Management
Oak Ridge National Laboratory
2020-2025
New York Medical College
2025
University of Tennessee at Knoxville
2020-2023
International AIDS Vaccine Initiative
2009-2022
Knoxville College
2020
University of Tennessee at Chattanooga
2018-2019
Virginia Commonwealth University
2015-2019
University of Toronto
1998-2012
University of Washington
1997-2005
Fred Hutch Cancer Center
2001-2004
Methionine synthase catalyzes the remethylation of homocysteine to methionine via a reaction in which methylcobalamin serves as an intermediate methyl carrier. Over time, cob(I)alamin cofactor becomes oxidized cob(II)alamin rendering enzyme inactive. Regeneration functional requires reductive methylation S -adenosylmethionine is utilized donor. Patients cblE complementation group disorders folate/cobalamin metabolism who are defective activation exhibit megaloblastic anemia, developmental...
Vitamin B 12 (cobalamin) is an essential cofactor of two enzymes, methionine synthase and methylmalonyl-CoA mutase. The conversion the vitamin to its coenzymes requires a series biochemical modifications for which several genetic diseases are known, comprising eight complementation groups ( cblA through cblH ). objective this study was clone gene responsible group thought represent mitochondrial cobalamin reductase. Examination bacterial operons containing genes in close proximity mutase...
Muscle contraction and relaxation is regulated by transient elevations of myoplasmic Ca(2+). Ca(2+) released from stores in the lumen sarco(endo)plasmic reticulum (SER) to initiate formation activation a class release channels referred as ryanodine receptors (RyRs) pumped back into SER Ca(2+)-ATPases (SERCAs) terminate transient. Mutations type 1 receptor gene, RYR1, are associated with 2 skeletal muscle disorders, malignant hyperthermia (MH), central core disease (CCD). The evaluation...
α-Crystallin B (cryAB) is the most abundant small heat shock protein in cardiomyocytes (CMs) and has been shown to have potent antiapoptotic properties. Because mechanism by which cryAB prevents apoptosis not fully characterized, we examined its protective effects at cellular level silencing mouse neonatal CMs using lentivector-mediated transduction of short hairpin RNAs. Subcellular fractionation whole hearts showed that cytosolic under control conditions, after H(2)O(2) exposure, it...
DNA priming has previously been shown to elicit augmented immune responses when administered by electroporation (EP) or codelivered with a plasmid encoding interleukin-12 (pIL-12). We hypothesized that the efficacy of prime and recombinant adenovirus 5 boost vaccination regimen (DNA/rAd5) would be improved incorporating these strategies into phase, as determined pathogenic simian immunodeficiency virus SIVmac239 challenge outcome. The whole proteome was delivered in separate plasmids...
Broadly neutralizing antibodies (bNAbs) PG9 and PG16 were isolated from an International AIDS Vaccine Initiative (IAVI) Protocol G subject infected with human immunodeficiency virus type 1 (HIV-1) clade A. Both are highly potent neutralize greater than 70% of viruses tested. We sought to begin immunogen design based on viral sequences this patient; however, pseudoviruses prepared 19 envelope resistant neutralization by PG16. Therefore, we used a bioinformatics approach identify closely...
SummaryBackgroundLassa fever (LF) is a zoonotic haemorrhagic disease caused by Lassa virus (LASV), which endemic in West African countries. The multimammate rat the main animal reservoir and its geographic range expected to expand due influences like climate change land usage, this will place larger parts of Africa at risk. We conducted preclinical development on promising experimental vaccine that allowed advancement into human trials.MethodsThe LF based vesicular stomatitis (VSV) vector...
Methionine synthase reductase (MSR) deficiency is an autosomal recessive disorder of folate/cobalamin metabolism leading to hyperhomocysteinemia, hypo-methioninemia and megaloblastic anemia. Deficiency in MSR activity occurs as the result a defect enzyme, which required for reductive activation methionine (MS). MS itself responsible folate/cobalamin-dependent conversion homo-cysteine methionine. We have recently cloned cDNA corresponding protein, novel member ferredoxin-NADP+ (FNR) family...
The ryanodine receptor (RyR) is a large, homotetrameric sarcoplasmic reticulum membrane protein that essential for Ca(2+) cycling in both skeletal and cardiac muscle. Genetic mutations RyR1 are associated with severe conditions including malignant hyperthermia (MH) central core disease. One phosphorylation site (Ser 2843) has been identified segment of flanked by two RyR motifs, which found exclusively all isoforms as closely tandem (or paired) named after the itself. These motifs also...
Electric power utilities employ "smart" re-closing devices capable of capturing electrical disturbance (ED) waveforms in real-time. These are digitally sampled, transmitted back to the utility, and stored text files that comply with IEEE COMmon format for TRAnsient Data Exchange (COMTRADE) standard. An average 2,100 ED events recorded, by 850 devices, on a monthly basis within Power Board's distribution network. Due operational restraints such as: time, money, person power, only 2% these...
To investigate a vaccine technology with potential to protect against coronavirus disease 2019 (COVID-19) and reduce transmission of severe acute respiratory syndrome 2 (SARS-CoV-2) single dose, we developed SARS-CoV-2 candidate using the live vesicular stomatitis virus (VSV) chimeric approach previously used develop licensed Ebola vaccine.We generated replication-competent VSV-SARS-CoV-2 by replacing VSV glycoprotein (G) gene coding sequence for Spike (S). Immunogenicity lead...
ABSTRACT The pathogenesis of tissue damage in chronic Trypanosoma cruzi infection has been a subject long-standing debate. Conventional staining methods reveal paucity parasites tissues from chronically infected individuals, which led to the theory that pathologic findings may be primarily autoimmune origin. Immunostaining for T. antigens or situ PCR show evidence parasite components tissues; however, these do not address whether stained material represents debris live organisms. An improved...
ABSTRACT Trypanosoma cruzi is the protozoan parasite that causes Chagas’ disease, a frequently fatal illness affecting heart and gastrointestinal systems. An estimated 16 million to 18 people in Latin America 50,000 100,000 United States are infected with this pathogen. Treatment options for T. infections suboptimal due toxicities limited effectiveness of available drugs. Azole antimicrobial agents have been discovered antitrypanosomal activity by inhibition ergosterol synthesis. The...
An estimated 12 million persons throughout the world suffer from protozoan disease leishmaniasis. Current treatments have liabilities including poor activity against some forms of leishmaniasis, toxicity, or need for parenteral administration. Higher throughput methods to screen chemical compounds are needed facilitate search new antileishmania drugs. In mammalian host, Leishmania parasites exist as amastigotes that replicate within macrophages. Therefore, an in vitro screening assay using...
ABSTRACT Trypanosoma cruzi is the protozoan agent that causes Chagas' disease, a major health problem in Latin America. Better drugs are needed to treat infected individuals. The sterol biosynthesis pathway potentially excellent target for drug therapy against T. . In this study, we investigated antitrypanosomal activities of series compounds designed inhibit key enzyme biosynthesis, oxidosqualene cyclase. This converts 2,3-oxidosqualene tetracyclic product, lanosterol. lead compound, N -(4...
Human immunodeficiency virus type 2 (HIV-2) infection is typically less virulent than HIV-1 infection, which may permit the host to mount more effective, sustained T-cell immunity. We investigated antiviral gamma interferon-secreting responses by an ex vivo Elispot assay in 68 HIV-1- and 55 HIV-2-infected Senegalese patients determine if differences relate efficient HIV-2 control. Homologous HIV-specific T cells were detected similar frequencies (79% versus 76%, P = 0.7) magnitude (3.12 3.08...
Abstract Naturally acquired cellular immunity in individuals who have been exposed to HIV-1 but remained uninfected may hold clues for the design of an effective HIV vaccine. To determine presence and nature such HIV-1-specific immune response, we evaluated quantity fine specificity HIV-1-reactive IFN-γ-secreting T cells a group highly seronegative men having sex with men. All 46 ES reported frequent unprotected anal known HIV-1-infected partners at enrollment, high risk activities continued...
Idiotypic IgM derived from a B cell lymphoma can act as tumor-associated Ag, in that immunization with this purified protein generates an anti-idiotypic immune response specifically suppresses tumor development. Spleens of mice contain T cells proliferate to idiotypic IgM. However, Ag is presented the most efficiently its natural form at surface cells, than soluble plus presenting cells. Variant tumors display either little or no surface, but which are otherwise indistinguishable parental...
Though vaccination with live-attenuated SIV provides the greatest protection from progressive disease caused by challenge in rhesus macaques, attenuated HIV presents safety concerns as a vaccine; therefore, live viral vectors carrying immunogens must be considered. We have designed replication-competent vesicular stomatitis virus (VSV) displaying immunogenic HIV-1 Env trimers and attenuating quantities of native surface glycoprotein (G). The clade B immunogen is an Env-VSV G hybrid (EnvG)...