A5080873765- Malaria Research and Control
- Ubiquitin and proteasome pathways
- Multiple Myeloma Research and Treatments
- Enzyme Structure and Function
- Trypanosoma species research and implications
- Protein Degradation and Inhibitors
- Mosquito-borne diseases and control
- Biochemical and Molecular Research
- Toxoplasma gondii Research Studies
- Peptidase Inhibition and Analysis
- Autophagy in Disease and Therapy
- COVID-19 epidemiological studies
- Glycosylation and Glycoproteins Research
- SARS-CoV-2 and COVID-19 Research
- RNA Interference and Gene Delivery
- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- Research on Leishmaniasis Studies
- Neuroblastoma Research and Treatments
- Cancer Cells and Metastasis
- Enzyme Production and Characterization
- Cancer-related gene regulation
- Vaccine Coverage and Hesitancy
- Viral Infectious Diseases and Gene Expression in Insects
- 3D Printing in Biomedical Research
Case Western Reserve University
2017-2025
Center for Global Health
2021-2024
University School
2017-2024
Brown University
2023
Intralytix (United States)
2017-2021
Johns Hopkins University
2011-2020
Pulmonary Associates
2020
Ashland (United States)
2018
University of Baltimore
2013
National Institute of Malaria Research
2013
A major cause of the paucity new starting points for drug discovery is lack interaction between academia and industry. Much global resource in biology present universities, whereas focus medicinal chemistry still largely within Open source discovery, with sharing information, clearly a first step towards overcoming this gap. But interface could especially be bridged through scale-up open physical compounds, which would accelerate finding discovery. The Medicines Malaria Venture Box...
Soluble egg antigens of the parasitic helminth Schistosoma mansoni (S. antigen [SEA]) induce strong Th2 responses both in vitro and vivo. However, specific molecules that prime development have not been identified. We report omega-1, a glycoprotein which is secreted from S. eggs present SEA, capable conditioning human monocyte-derived dendritic cells to drive T helper 2 (Th2) polarization with similar characteristics as whole SEA. Furthermore, using IL-4 dual reporter mice, we show natural...
Introduction of monovalent COVID-19 mRNA vaccines in late 2020 helped to mitigate disproportionate COVID-19-related morbidity and mortality U.S. nursing homes (1); however, reduced effectiveness during the period Omicron variant predominance led recommendations for booster doses with bivalent that include an BA.4/BA.5 spike protein component broaden immune response improve vaccine against circulating variants (2). Recent studies suggest provide substantial additional protection SARS-CoV-2...
A gradient of microcapillary networks and microfluidic anastomoses enable standardized quantitative assessment red blood cell mediated microvascular occlusion.
Emerging and re-emerging viral diseases pose continuous public health threats, effective control requires a combination of non-pharmacologic interventions, treatment with antivirals, prevention vaccines. The COVID-19 pandemic has demonstrated that the world was least prepared to provide treatments. This lack preparedness been due, in large part, investment developing diverse portfolio antiviral agents, particularly those ready combat viruses potential. Here, we focus on drug target called...
An actomyosin motor located underneath the plasma membrane drives motility and host-cell invasion of apicomplexan parasites such as Plasmodium falciparum vivax, causative agents malaria. Aldolase connects actin filaments to transmembrane adhesive proteins thrombospondin-related anonymous protein (TRAP) family transduces force across parasite surface. The TRAP-aldolase interaction is a distinctive critical trait host hepatocyte by sporozoites, with likely similar crucial for erythrocyte...
Latent cytomegalovirus (CMV) infection is immunomodulatory and could affect mRNA vaccine responsiveness. We sought to determine the association of CMV serostatus prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with antibody (Ab) titers after primary booster BNT162b2 vaccinations in healthcare workers (HCWs) nursing home (NH) residents. Nursing residents (N = 143) HCWs 107) were vaccinated serological responses monitored by serum neutralization activity against Wuhan...
Background: The COVID-19 pandemic has greatly affected nursing home residents (NHRs), a vulnerable group with high rates of illness and death. While vaccination is essential for reducing infections severe outcomes in the short term, it important to understand how long antibody levels neutralizing activity last. This understanding will help us create effective public health strategies term. According current CDC guidelines, individuals over age 65 should receive booster dose six months after...
Abstract Background The FDA recently approved the first monovalent XBB1.5 booster vaccine. However, mechanism by which this vaccine stimulates mucosal and systemic immune responses has been understudied.Figure 1.Impact of XBB 1.5 vaccination on viral neutralization titers using pseudo virus assay (left panel) ACE2 inhibition (right panel).Each dot (white) represents a single serum sample tested in parallel with post-vaccination (colored dot) for each 28 participants. mean fold increase pre-...
The causative agents of malaria have developed a sophisticated machinery for entering multiple cell types in the human and insect hosts. In this machinery, critical interaction occurs between unusual myosin motor MyoA MyoA-tail Interacting Protein (MTIP). Here we present one crystal structure that shows three different conformations Plasmodium MTIP, these complex with MyoA-tail, which reveal major conformational changes C-terminal domain MTIP upon binding helix, thereby creating several...
The temperature dependence of fatty acid spin label resonance spectra and freeze fracture micrographs sonicated dipalmitoylphosphatidylcholine vesicles in the absence presence concanavalin A demonstrate a strong interaction with these lipid membranes, which results fusion vesicles. rate this reaction as followed use magnetic exhibits pronounced maximum at 36 degrees, midpoint phase transition range This is discussed terms structural fluctuations, are maximal membranes.
Atg8 is a ubiquitin-like autophagy protein in eukaryotes that covalently attached (lipidated) to the elongating autophagosomal membrane. Autophagy increasingly appreciated as target diverse diseases from cancer eukaryotic parasitic infections. Some of machinery conserved malaria parasite, Plasmodium. Although Atg8's function parasite not well understood, it essential for Plasmodium growth and survival partially localizes apicoplast, an indispensable organelle apicomplexans. Here, we describe...
Abstract The Chromobacterium sp . Panama bacterium has in vivo and vitro anti- Plasmodium properties. To assess the nature of -produced factors, chemical partition was conducted by bioassay-guided fractionation where different fractions were assayed for activity against asexual stages P. falciparum isolated compounds further partitioned reversed-phase FPLC followed size-exclusion chromatography; high resolution UPLC ESI/MS data then collected revealed that most active fraction contained a...
The 1.8 Å resolution de novo structure of nucleoside 2-deoxyribosyltransferase (EC 2.4.2.6) from Trypanosoma brucei (TbNDRT) has been determined by SADa phasing in an unliganded state and several ligand-bound states. This enzyme is important the salvage pathway recycling. To identify novel lead compounds, we exploited "fragment cocktail soaks". Out 304 compounds tried 31 cocktails, four could be identified crystallographically active site. In addition, demonstrated that very short soaks ∼10...
Plasmodium parasites successfully colonize different habitats within mammals and mosquitoes, adaptation to various environments is accompanied by changes in their organelle composition size. Previously, we observed that during hepatocyte infection, discards organelles involved invasion expands those implicated biosynthetic pathways. We hypothesized this process regulated autophagy. spp. possess a rudimentary set of known autophagy-related proteins includes the ortholog yeast Atg8. In study,...
Abstract 1‐Deoxy‐ D ‐xylulose 5‐phosphate (DXP) synthase catalyzes the first step in nonmammalian isoprenoid biosynthetic pathway to form DXP from pyruvate and ‐glyceraldehyde 3‐phosphate ( ‐GAP) a thiamin diphosphate‐dependent manner. Its unique structure mechanism distinguish its homologues suggest that it should be pursued as an anti‐infective drug target. However, few reports describe any development of selective inhibitors this enzyme. Here, we reveal CN bond formation exploit aromatic...
S-nitroso-l-cysteine (L-CSNO) behaves as a ligand. Its soluble guanylate cyclase-independent (sGC-independent) effects are stereoselective - that is, not recapitulated by S-nitroso-d-cysteine (D-CSNO) and inhibited chemical congeners. However, candidate L-CSNO receptors have been identified. Here, we used 2 complementary affinity chromatography assays followed unbiased proteomic analysis to identify voltage-gated K+ channel (Kv) proteins binding partners for L-CSNO. Stereoselective L-CSNO-Kv...