- Malaria Research and Control
- Bioactive natural compounds
- Phytochemicals and Antioxidant Activities
- Multiple Myeloma Research and Treatments
- Mosquito-borne diseases and control
- Synthesis of Organic Compounds
- Trypanosoma species research and implications
- Genomics, phytochemicals, and oxidative stress
- Cell death mechanisms and regulation
- Oral Health Pathology and Treatment
- Immunotherapy and Immune Responses
- RNA and protein synthesis mechanisms
- Cancer-related Molecular Pathways
- Complement system in diseases
- Immune Cell Function and Interaction
- Enzyme Production and Characterization
- Pharmacogenetics and Drug Metabolism
- Viral gastroenteritis research and epidemiology
- Cancer therapeutics and mechanisms
- Drug Transport and Resistance Mechanisms
- Berry genetics and cultivation research
- Synthesis and Biological Evaluation
- Retinoids in leukemia and cellular processes
- Carcinogens and Genotoxicity Assessment
- RNA Research and Splicing
Penn State Milton S. Hershey Medical Center
2015-2025
Pennsylvania State University
2015-2025
Lucigen Corporation
2010-2017
Aurigene Discovery Technologies (India)
2017
Johns Hopkins Medicine
2013-2016
Johns Hopkins University
2013-2016
Great Lakes Bioenergy Research Center
2010-2016
University of Wisconsin–Madison
2016
Hershey (United States)
2007-2014
National Chemical Laboratory
2008-2013
The glycosylphosphatidylinositol (GPI) anchors of Plasmodium falciparum have been proposed to be the major factors that contribute malaria pathogenesis through their ability induce proinflammatory responses. In this study we identified receptors for P. GPI-induced cell signaling leads responses and studied GPI structure-activity relationship. data show is mediated mainly recognition by TLR2 a lesser extent TLR4. activity sn-2-lyso-GPIs comparable with intact GPIs, whereas Man(3)-GPIs about...
Abstract Ligand activation of the aryl hydrocarbon (AHR) has profound effects upon immunological status gastrointestinal tract, establishing and maintaining signaling networks, which facilitate host-microbe homeostasis at mucosal interface. However, identity ligand(s) responsible for such AHR-mediated within gut remains to be firmly established. Here, we combine in vitro ligand binding, quantitative gene expression, protein-DNA interaction structure activity analyses together with silico...
High enzyme loading is a major economic bottleneck for the commercial processing of pretreated lignocellulosic biomass to produce fermentable sugars. Optimizing cocktail specific types allows significant reduction in without sacrificing hydrolysis yield. This especially important alkaline pretreatments such as Ammonia fiber expansion (AFEX) corn stover. Hence, diverse set hemicellulases supplemented along with cellulases necessary high recovery monosaccharides.The core fungal optimal include...
Commensal microbiota-dependent tryptophan catabolism within the gastrointestinal tract is known to exert profound effects upon host physiology, including maintenance of epithelial barrier and immune function. A number abundant microbiota-derived metabolites exhibit activation potential for aryl hydrocarbon receptor (AHR). Gene expression facilitated by AHR through presence dietary or microbiota-generated can influence homeostasis confer protection from intestinal challenges. Utilizing...
The anti-apoptotic Bcl-2 family of proteins, including Bcl-2, Bcl-X<sub>L</sub> and Mcl-1, are well-validated drug targets for cancer treatment. Several small molecules have been designed to interfere with its fellow pro-survival members. While ABT-737 orally active analog ABT-263 the most potent specific inhibitors date that bind high affinity but a much lower they not very effective as single agents in certain types because elevated levels Mcl-1. Accordingly, compounds specifically target...
Dendritic cells (DCs) play a crucial role in the development of protective immunity to malaria. However, it remains unclear how malaria parasites trigger immune responses DCs. In this study, we purified merozoites, food vacuoles, and parasite membrane fragments released during Plasmodium falciparum schizont burst homogeneity tested for activation bone marrow-derived DCs from wild-type TLR2(-/-), TLR4(-/-), TLR9(-/-), MyD88(-/-) C57BL/6J mice. The results demonstrate that protein-DNA complex...
The signal recognition particle (SRP) is a ribonucleoprotein composed of an Alu domain and S domain. contains unique sequence SRP RNA four proteins: SRP19, SRP54, SRP68, SRP72. interacts with ribosomes to bring translating membrane secreted proteins the endoplasmic reticulum (ER) for proper processing. Additionally, member family small nonribosomal RNAs found recently in nucleolus, suggesting that nucleolus more plurifunctional than previously realized. It was therefore interest determine...
The glycosylphosphatidylinositol (GPI) anchors of Plasmodium falciparum have been proposed to be the major factors that contribute malaria pathogenesis by eliciting production proinflammatory cytokines and nitric oxide host innate immune system. In this study we demonstrate parasite GPIs can effectively induce TNF-α at 5-20 nm concentrations in interferon-γ-primed monocytes macrophages. potency activity is physiologically relevant their ability severe pathogenesis. More importantly,...
The concept of selective receptor modulators has been established for the nuclear steroid hormone receptors. Such have used therapeutically with great success in treatment cancer. However, this not examined regard to aryl hydrocarbon (AHR) because latent toxicity commonly associated AHR activation. AHR-mediated is primarily derived from binding its dioxin response element (DRE) and driving expression CYP1 family members, which capacity metabolize procarcinogens genotoxic carcinogens. Recent...
Effective resolution of malaria infection by avoiding pathogenesis requires regulated pro- to anti-inflammatory responses and the development protective immunity. TLRs are known be critical for initiating innate immune responses, but their roles in regulation immunity remain poorly understood. In this study, using wild-type, TLR2(-/-), TLR4(-/-), TLR9(-/-), MyD88(-/-) mice infected with Plasmodium yoelii, we show that TLR9 MyD88 regulate pro/anti-inflammatory cytokines, Th1/Th2 development,...
ABSTRACT Malaria parasite ( Plasmodium spp.) infection in the mosquito Anopheles stephensi induces significant expression of A. nitric oxide synthase (AsNOS) midgut epithelium as early 6 h postinfection and intermittently thereafter. This induction results synthesis inflammatory levels (NO) blood-filled that adversely impact development. In mammals, P. falciparum glycosylphosphatidylinositols (PfGPIs) can induce NOS immune endothelial cells are sufficient to reproduce major effects...
Human rotaviruses were isolated from asymptomatic neonates at various hospitals and clinics in the city of Bangalore, India, found to be subgroup I specific possess long RNA patterns (M. Sukumaran, K. Gowda, P. Maiya, T. Srinivas, M. S. Kumar, Aijaz, R. Reddy, L. Padilla, H. B. Greenberg, C. D. Rao, Arch. Virol. 126:239-251, 1992). Three these strains adapted tissue culture by serotype analysis neutralization assays 10, a commonly cattle but infrequently humans not previously identified...
The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin. However, role AHR in normal physiology still an area intense investigation. For example, this plays important certain immune responses. We have previously determined can mediate repression acute-phase genes liver. observation to be therapeutically useful, selective activation would likely necessary. Recently, estrogen ligand WAY-169916 has also...
The aryl hydrocarbon receptor (AhR) has been shown to play a role in an increasing number of cellular processes. Recent reports have linked the AhR cell proliferation, cytoskeletal arrangement, and tumor invasiveness various types. plays de-repression interleukin (IL)6 promoter certain lines, allowing for increased transcriptional activation by cytokines. Here, we show that there is significant level constitutive cells isolated from patients with head neck squamous carcinoma (HNSCC)....
Viral metagenomic libraries are a promising but previously untapped source of new reagent enzymes. Deep sequencing and functional screening viral DNA from near-boiling thermal pool identified clones expressing thermostable polymerase (Pol) activity. Among these, 3173 Pol demonstrated both high thermostability innate reverse transcriptase (RT) We describe the biochemistry report its use in single-enzyme transcription PCR (RT-PCR). Wild-type contains proofreading 3′-5′ exonuclease domain that...
The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that plays an integral role in homeostatic maintenance by regulating cellular functions such as differentiation, metabolism, barrier function, and immune response. An important but poorly understood class of AHR activators are compounds derived from host bacterial metabolism tryptophan. commensal bacteria the gut microbiome major producers tryptophan metabolites known to activate AHR, while also produces through...
The systemic clinical symptoms of Plasmodium falciparum infection such as fever and chills correspond to the proinflammatory cytokines produced in response parasite components released during synchronized rupture schizonts. We recently demonstrated that, among schizont-released products, merozoites are predominant that activate dendritic cells (DCs) by TLR9-specific recognition induce maturation produce cytokines. also DNA is active constituent formation a DNA-protein complex essential for...
<h3>Objectives</h3> Rheumatoid Arthritis (RA) is a chronic inflammatory disease of unclear aetiology, which associated with inflamed human fibroblast-like synoviocytes (HFLS). Epidemiological studies have identified positive correlation between tobacco smoking (a rich source aryl hydrocarbon receptor (AHR) agonists) and aggressive RA phenotype. Thus, we hypothesise that antagonism AHR activity by potent antagonist GNF351 can attenuate the phenotype HFLS-RA cells. <h3>Methods</h3>...