A5015906208- Viral gastroenteritis research and epidemiology
- Developmental Biology and Gene Regulation
- Retinal Development and Disorders
- Animal Virus Infections Studies
- Genomics and Chromatin Dynamics
- Virus-based gene therapy research
- Digestive system and related health
- Escherichia coli research studies
- Neurobiology and Insect Physiology Research
- Viral Infections and Immunology Research
- Clostridium difficile and Clostridium perfringens research
- 3D Printing in Biomedical Research
- Infant Nutrition and Health
- Protein Kinase Regulation and GTPase Signaling
- Animal Genetics and Reproduction
- Gut microbiota and health
- Microtubule and mitosis dynamics
- Pancreatic function and diabetes
- RNA Research and Splicing
- Axon Guidance and Neuronal Signaling
- Clinical Nutrition and Gastroenterology
- Chemokine receptors and signaling
- Genetics and Neurodevelopmental Disorders
- Advanced Thermodynamic Systems and Engines
- 14-3-3 protein interactions
Baylor College of Medicine
2013-2024
West Virginia University
2001-2009
Morgantown High School
2005
University of California, San Diego
2005
Hebrew University of Jerusalem
2005
The major barrier to research and development of effective interventions for human noroviruses (HuNoVs) has been the lack a robust reproducible in vitro cultivation system. HuNoVs are leading cause gastroenteritis worldwide. We report successful multiple HuNoV strains enterocytes stem cell–derived, nontransformed intestinal enteroid monolayer cultures. Bile, critical factor milieu, is required strain-dependent replication. Lack appropriate histoblood group antigen expression cells restricts...
Human gastrointestinal tract research is limited by the paucity of in vitro intestinal cell models that recapitulate cellular diversity and complex functions human physiology disease pathology. enteroid (HIE) cultures contain multiple epithelial types comprise epithelium (enterocytes goblet, enteroendocrine, Paneth cells) are physiologically active based on responses to agonists. We evaluated these nontransformed, three-dimensional HIE as for pathogenic infections small intestine examining...
The intestinal epithelium can limit enteric pathogens by producing antiviral cytokines, such as IFNs. Type I IFN (IFN-α/β) and type III (IFN-λ) function at the epithelial level, their respective efficacies depend on specific pathogen site of infection. However, roles in restricting human viruses are poorly characterized a result difficulties cultivating these vitro directly obtaining control infected small tissue. We nontransformed enteroid cultures from multiple individuals with rotavirus...
Human noroviruses (HuNoVs) can often cause chronic infections in solid organ and haematopoietic stem cell transplant (HSCT) patients. Based on histopathological changes observed during HuNoV infections, the intestine is presumed site of virus replication patients; however, types infected by HuNoVs remain unknown. The objective this study was to characterize infection determine that may be permissive for We analysed biopsies from HuNoV-infected non-infected (control) patients assess...
Significance Many viral pathogens replicate in the human small intestine where they must invade epithelial barrier that has evolved to protect host against microbial assaults. Using a norovirus strain requires bile stem cell-derived intestinal enteroid cultures, we found conjugated hydrophobic acids and ceramide are critical allow virus entry subsequent replication jejunal enteroids. Glycochenodeoxycholic acid treatment of enteroids below micellar concentration leads multiple cellular...
Several studies have demonstrated that secretor status is associated with susceptibility to human norovirus (HuNoV) infection; however, previous reports found FUT2 expression not sufficient allow infection HuNoV in a variety of continuous laboratory cell lines. Which cellular factor(s) regulates remains unknown. We used genetic manipulation HIE cultures show determined by gene necessary and support replication based on analyses isogenic lines lack or express FUT2. Fucosylation HBGAs critical...
Human noroviruses (HuNoVs) are the leading cause of viral gastroenteritis worldwide; yet currently, no vaccines or FDA-approved antiviral drugs available to counter these pathogens. To understand HuNoV biology and epithelial response infection, we performed transcriptomic analyses, RT-qPCR, CRISPR-Cas9 modification human intestinal enteroid (HIE) cultures, functional studies with two virus strains (a pandemic GII.4 a bile acid-dependent GII.3 strain). We identified predominant type III...
Enteroendocrine cells (EECs) are specialized epithelial that produce molecules vital for intestinal homeostasis, but because of their limited numbers, in-depth functional studies have remained challenging. Human enteroids (HIEs) derived from crypt stem biologically relevant in an vitro model the epithelium. HIEs contain all cell types; however, similar to intestine, spontaneously few EECs, which limits study.
Abstract Globally, most cases of gastroenteritis are caused by pandemic GII.4 human norovirus (HuNoV) strains with no approved therapies or vaccines available. The cellular pathways that these exploit for cell entry and internalization unknown. Here, using nontransformed jejunal enteroids (HIEs) recapitulate the physiology gastrointestinal tract, we show infectious virions virus-like particles endocytosed a unique combination endosomal acidification-dependent clathrin-independent carriers...
Gastroenteritis is among the leading causes of mortality globally in infants and young children, with rotavirus (RV) causing ~258 million episodes diarrhea ~128,000 deaths annually children. RV-induced mechanisms that result are not completely understood, but malabsorption a contributing factor. RV alters cellular lipid metabolism by inducing droplet (LD) formation as platform for replication factories named viroplasms. A link between LD gastroenteritis has been identified. We found...
Enteroaggregative Escherichia coli (EAEC) is a significant cause of acute and chronic diarrhea, foodborne outbreaks, infections the immunocompromised, growth stunting in children developing nations. There no vaccine resistance to antibiotics rising. Unlike related E. pathotypes that are often associated with bouts infection, EAEC persistent diarrhea subclinical long-term colonization. Several secreted virulence factors have been pathogenesis linked disease humans, less certain molecular...
Mechanistic investigation of host-microbe interactions in the human gut are hindered by difficulty co-culturing microbes with intestinal epithelial cells. On one hand bacteria a mix facultative, aerotolerant or obligate anaerobes, while epithelium requires oxygen for growth and function. Thus, coculture system that can recreate these contrasting requirements is critical step towards our understanding microbial-host gut. Here, we demonstrate Intestinal Organoid Physoxic Coculture (IOPC)...
Drosophila Groucho, like its vertebrate Transducin-like Enhancer-of-split homologues, is a corepressor that silences gene expression in numerous developmental settings.Groucho itself does not bind DNA but recruited to target promoters by associating with large number of DNA-binding negative transcriptional regulators.These repressors tether Groucho via short conserved polypeptide sequences, which two have been defined.First, WRPW and related tetrapeptide motifs well characterized several...
In vitro data suggest that the human RbAp46 and RbAp48 genes encode proteins involved in multiple chromatin remodeling complexes are likely to play important roles development tumor suppression. However, date, our understanding of role RbAp46/RbAp48 its homologs metazoan disease has been hampered by a lack insect mammalian mutant models, as well redundancy due orthologs most organisms studied. Here, we report first mutations single Drosophila homolog Caf1, identified strong suppressors...
Homeodomain transcription factors of the Sine oculis (SIX) family direct multiple regulatory processes throughout metazoans. (So) was first characterized in fruit fly Drosophila melanogaster, where it is both necessary and sufficient for eye development, regulating cell survival, proliferation, differentiation. Despite its key role only a few targets So have been described previously. In current study, we aim to expand our knowledge So-mediated transcriptional regulation developing using...
In Drosophila, development of the compound eye is orchestrated by a network highly conserved transcriptional regulators known as retinal determination (RD) network. The gene eyes absent (eya) expressed in most cells within developing field, from undifferentiated progenitors to photoreceptor whose differentiation begins at morphogenetic furrow (MF). Loss eya expression leads an early block development, making it impossible study role during later steps differentiation. We have identified two...
The eye of the fruit fly Drosophila melanogaster provides a highly tractable genetic model system for study animal development, and many genes that regulate formation have homologs implicated in human development disease. Among these is homeobox gene sine oculis (so), which encodes homeodomain transcription factor (TF) both necessary sufficient to reprogram subset cells outside normal field toward an fate. We performed genome-wide analysis So binding DNA prepared from developing tissue order...