A5086954734- Helicobacter pylori-related gastroenterology studies
- Galectins and Cancer Biology
- Gastric Cancer Management and Outcomes
- Gastrointestinal disorders and treatments
- RNA modifications and cancer
- Eosinophilic Esophagitis
- Cancer Research and Treatments
- MicroRNA in disease regulation
- Pancreatic and Hepatic Oncology Research
- Iron Metabolism and Disorders
- Veterinary medicine and infectious diseases
- Digestive system and related health
- Cancer, Hypoxia, and Metabolism
- Clostridium difficile and Clostridium perfringens research
- Cancer-related gene regulation
- IL-33, ST2, and ILC Pathways
- Gut microbiota and health
- Porphyrin Metabolism and Disorders
- Peptidase Inhibition and Analysis
- Diagnosis and treatment of tuberculosis
- Mycobacterium research and diagnosis
- Cancer-related molecular mechanisms research
- Folate and B Vitamins Research
- Kruppel-like factors research
- Potassium and Related Disorders
Vanderbilt University Medical Center
2014-2023
Vanderbilt University
2010-2018
Nashville Oncology Associates
2015
Virginia Commonwealth University Medical Center
2008-2012
VA Tennessee Valley Healthcare System
2010
Virginia Commonwealth University
2009
Gastric adenocarcinoma is strongly associated with Helicobacter pylori infection; however, most infected persons never develop this malignancy. H. strains harboring the cag pathogenicity island (cag+), which encodes CagA and a type IV secretion system (T4SS), induce more severe disease outcomes. infection also iron deficiency, similarly augments gastric cancer risk. To define influence of deficiency on microbial virulence in carcinogenesis, Mongolian gerbils were maintained iron-depleted...
Helicobacter pylori (Hp) injects the CagA effector protein into host epithelial cells and induces growth factor-like signaling, perturbs cell-cell junctions, alters cell polarity. This enables Hp to grow as microcolonies adhered surface even in conditions that do not support of free-swimming bacteria. We hypothesized physiology allow obtain specific nutrients from or across barrier. Using a polarized epithelium model system, we find isogenic ΔcagA mutants are defective microcolony formation,...
<h3>Objective</h3> <i>Helicobacter pylori</i> strains that express the oncoprotein CagA augment risk for gastric cancer. However, precise mechanisms through which <i>cag</i><sup>+</sup> heighten cancer have not been fully delineated and model systems recapitulate niche are critical understanding pathogenesis. Gastroids three-dimensional organ-like structures provide unique opportunities to study host-<i>H. interactions in a preclinical model. We used gastroids inform direct vitro studies...
The stem cell in the isthmus of gastric units continually replenishes epithelium. Atrophy acid-secreting parietal cells (PCs) frequently occurs during infection with Helicobacter pylori, predisposing patients to cancer. causes increased proliferation cells, yet little is known about how this process regulated. Here we show that CD44 labels a population small, undifferentiated unit where are reside. Loss vivo results decreased When induce PC atrophy by or tamoxifen treatment, CD44(+) expands...
Gastric carcinogenesis is mediated by complex interactions among Helicobacter pylori, host, and environmental factors. Here, we demonstrate that H. pylori augmented gastric injury in INS-GAS mice under iron-deficient conditions. Mechanistically, these phenotypes were not driven alterations the microbiota; however, discovery-based targeted metabolomics revealed bile acids significantly altered pylori–infected with iron deficiency, significant upregulation of deoxycholic acid (DCA), a...
<h3>Objective</h3> Infection with <i>Helicobacter pylori</i> is the strongest known risk factor for adenocarcinoma of stomach. Tumorigenic transformation gastric epithelium induced by <i>H. a highly complex process driven an active interplay between bacterial virulence and host factors, many aspects which remain obscure. In this work, we investigated degradation p53 tumour suppressor pylori</i>. <h3>Design</h3> Expression protein in biopsies was assessed immunohistochemistry. Gastric cells...
Chronic mucosal pathogens have evolved multiple strategies to manipulate the host immune response; consequently, microbes contribute development of >2 million cases cancer/year. Gastric adenocarcinoma is fourth leading cause cancer-related death and Helicobacter pylori confers highest risk for this disease. innate effectors can either eliminate bacteria or mobilize adaptive responses including Toll-like receptors (TLRs), cytosolic DNA sensor/adaptor proteins (e.g., stimulator interferon...
The p53 protein plays a central role in the prevention of tumorigenesis. Cellular stresses, such as DNA damage and aberrant oncogene activation, trigger induction that halts cellular proliferation allows cells to be repaired. If is beyond capability repair mechanisms, induces apoptosis or cell cycle arrest, preventing damaged from becoming cancerous. However, emerging evidence suggests function needs considered isoform-specific. Here, we report expression profile can shifted toward...
Helicobacter pylori is the strongest known risk factor for development of gastric adenocarcinoma. H. expresses a repertoire virulence factors that increase cancer risk, including cag pathogenicity island and vacuolating cytotoxin (VacA). One host element promotes carcinogenesis within gastrointestinal tract Krüppel-like 5 (KLF5), transcription mediates key cellular functions. To define role KLF5 context pylori-induced inflammation injury, human epithelial cells were co-cultured with...
Helicobacter pylori is the strongest risk factor for gastric cancer, and strains harboring cag pathogenicity island, which translocates oncoprotein CagA into host cells, further augment cancer risk. We previously reported that in vivo adaptation of a noncarcinogenic H. strain (B128) generated derivative (7.13) with ability to induce adenocarcinoma, providing unique opportunity define mechanisms mediate carcinogenesis. MicroRNAs (miRNAs) are small noncoding RNAs regulate expression oncogenes...
Spasmolytic polypeptide-expressing metaplasia (SPEM) and intestinal are considered neoplastic precursors of gastric adenocarcinoma in humans. Loss parietal cells causes the development SPEM corpus then chronic inflammation drives toward a more proliferative lineage. Mongolian gerbils infected with Helicobacter pylori develop gastritis metaplasia, mimicking aspects human H. infection. We therefore examined metaplastic lineages mucosa by strain 7.13, which produces rapid onset severe...
// Vikas Bhardwaj 1, 2 , Jennifer M. Noto 4 Jinxiong Wei Claudia Andl 2, 3 Wael El-Rifai Richard Peek 3, Alexander I. Zaika 1 Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, Tennessee, USA Surgery, Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center, Biology, Division Gastroenterology, Correspondence to: Zaika, e-mail: alex.zaika@vanderbilt.edu Keywords: p53, Helicobacter pylori gastric tumor, HDM2, CagA Abbreviations: -...
Helicobacter pylori-induced inflammation is the strongest known risk factor for gastric adenocarcinoma. Hypoxia-inducible factor-1 (HIF-1α) a key transcriptional regulator of immunity and carcinogenesis. To examine role this mediator within context H. injury, we first demonstrated that HIF-1α levels were significantly increased in parallel with severity lesions humans. In interventional studies targeting HIF-1α, pylori-infected mice treated ± dimethyloxalylglycine (DMOG), prolyl hydroxylase...
Acute Helicobacter pylori infection of gastric epithelial cells induces CagA oncoprotein- and peptidoglycan (SLT)-dependent mobilization NF-κB p50 homodimers that bind to H-K-ATPase α-subunit (HKα) promoter repress HKα gene transcription. This process may facilitate H. colonization by induction transient hypochlorhydria. We hypothesized also regulates expression posttranscriptionally miRNA interaction with mRNA. In silico analysis the 3′ untranslated region (UTR) identified miR-1289 as a...
Microbial communities are essential for the maintenance of human health, and when these altered, hosts can become susceptible to inflammation disease. Dysbiosis contributes gastrointestinal cancers, specific bacterial species associated with this phenotype. This study uses a robust reproducible animal model demonstrate that H. pylori infection induces gastric dysbiosis in cagA -dependent manner further altered microbial community structure parallel severity -induced injury. Ultimately, such...
Neisseria gonorrhoeae requires iron for survival in the human host and therefore expresses high-affinity receptors acquisition from iron-binding proteins. The gonococcal transferrin-iron uptake system is composed of two transferrin binding proteins, TbpA TbpB. a TonB-dependent, outer membrane transporter critical acquisition, while TbpB surface-exposed lipoprotein that increases efficiency uptake. precise mechanism by which mediates has not been elucidated; however, process distinct those...
Neisseria gonorrhoeae has the capacity to acquire iron from its human host by removing this essential nutrient serum transferrin. The transferrin binding proteins, TbpA and TbpB, constitute outer membrane receptor complex responsible for transferrin, extracting tightly bound host-derived molecule, transporting into periplasmic space of Gram-negative bacterium. Once is transported across membrane, ferric protein A (FbpA) moves initiates process transport bacterial cytosol. results studies...