A5054462317- Vibrio bacteria research studies
- Malaria Research and Control
- Salmonella and Campylobacter epidemiology
- HIV Research and Treatment
- Complement system in diseases
- Aquaculture disease management and microbiota
- Prenatal Screening and Diagnostics
- Escherichia coli research studies
- Hemoglobinopathies and Related Disorders
- Lipid Membrane Structure and Behavior
- Cassava research and cyanide
- Child Nutrition and Water Access
- Protein Degradation and Inhibitors
- PARP inhibition in cancer therapy
- Epigenetics and DNA Methylation
- Mosquito-borne diseases and control
- Yersinia bacterium, plague, ectoparasites research
- Calcium signaling and nucleotide metabolism
- Parvovirus B19 Infection Studies
Harvard University
2017-2021
University of Rochester
2011-2016
ABSTRACT AM-19226 is a pathogenic O39 serogroup Vibrio cholerae strain that lacks the typical virulence factors for colonization (toxin-coregulated pilus [TCP]) and toxin production (cholera [CT]) instead encodes type III secretion system (T3SS). The mechanism of pathogenesis unknown, few effector proteins have been identified. We therefore undertook survey open reading frames (ORFs) within ∼49.7-kb T3SS genomic island to identify potential proteins. identified 15 ORFs their ability inhibit...
Significance During malaria infections, Plasmodium falciparum parasites invade RBCs. Identification of host factors for parasite invasion guides the development vaccines and host-targeted therapeutics. Here we describe an in vitro culture system functional analysis RBC determinants using immortal erythroleukemia cell line JK-1. JK-1 cells can be induced to differentiate synchronously, support invasion, are amenable genetic manipulation. Using this system, validated two factors, basigin CD44,...
ABSTRACT Vibrio cholerae is a genetically diverse species, and pathogenic strains can encode different virulence factors that mediate colonization secretory diarrhea. Although the toxin-coregulated pilus (TCP) primary factor in epidemic-causing V. strains, other do not TCP instead promote via activity of type 3 secretion system (T3SS). Using infant mouse model T3SS-positive O39 serogroup strain AM-19226, we sought to determine which 12 previously identified, T3SS-translocated proteins (Vops)...
Abstract Malaria pathogenesis is caused by the replication of Plasmodium parasites within red blood cells (RBCs) vertebrate host. This selective pressure has favored evolution protective polymorphisms in erythrocyte proteins, a subset which serve as cognate receptors for parasite invasion ligands. Recently, generation RBCs from immortalized hematopoietic stem (HSCs) offered more tractable system genetic manipulation and long‐term vitro culture, enabling elucidation functional determinants...
Plasmodium vivax has 2 invasion ligand/host receptor pathways (P. Duffy-binding protein/Duffy antigen for chemokines [DARC] and P. reticulocyte binding protein 2b/transferrin [TfR1]) that are promising targets therapeutic intervention. We optimized assays with isogenic cultured reticulocytes. Using a blockade approach multiple isolates, we found all strains utilized both DARC TfR1, but significant variation in usage. This suggests vivax, like falciparum, uses alternative pathways,...
Human genetics has validated de-repression of fetal gamma globin (HBG) in adult erythroblasts as a powerful therapeutic paradigm diseases involving defective beta (HBB)1. To identify factors involved the switch from HBG to HBB expression, we performed Assay for Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq)2 on sorted erythroid lineage cells derived bone marrow (BM) or cord blood (CB), representing and states, respectively. BM CB cell ATAC-seq profile comparisons...
Plasmodium falciparum, the parasite that causes deadliest form of malaria, has evolved multiple proteins known as invasion ligands bind to specific erythrocyte receptors facilitate human erythrocytes. The EBA-175/glycophorin A (GPA) and Rh5/basigin ligand-receptor interactions, referred pathways, have been subject intense study. In this study, we focused on less-characterized sialic acid-containing glycophorin B (GPB) C (GPC). Through bioinformatic analysis, identified extensive variation in...
A subset of non-O1/non-O139 serogroup strains Vibrio cholerae cause disease using type 3 secretion system (T3SS)-mediated mechanisms. An ∼50-kb genomic island carries genes encoding the T3SS structural apparatus, effector proteins, and two transmembrane transcriptional regulators, VttR(A) VttR(B), which are ToxR homologues. Previous experiments demonstrated that VttR(B) necessary for colonization in vivo promote bile-dependent gene expression vitro. To better understand scope potential...
AM-19226 is a pathogenic, non-O1/non-O139 serogroup strain of Vibrio cholerae that uses Type 3 Secretion System (T3SS) mediated mechanism to colonize host tissues and disrupt homeostasis, causing cholera. Co-culturing the Caco2-BBE human intestinal epithelial cell line with in presence bile results rapid mammalian death requires functional T3SS. We examined role bile, sought identify mechanism, evaluated contributions T3SS translocated effectors vitro death. Our suggest cytotoxicity does not...
Abstract Cholesterol-rich microdomains are membrane compartments characterized by specific lipid and protein composition. These dynamic assemblies involved in several biological processes, including infection intracellular pathogens. This work provides a comprehensive analysis of the composition human erythrocyte microdomains. Based on their floating properties, we also categorized microdomain-associated proteins into clusters. Interestingly, include vast majority known to be invasion...