A5018586893- FOXO transcription factor regulation
- Inflammatory Bowel Disease
- Lipid metabolism and biosynthesis
- Escherichia coli research studies
- Gut microbiota and health
- Musculoskeletal synovial abnormalities and treatments
- Sarcoma Diagnosis and Treatment
- Ear and Head Tumors
- Helicobacter pylori-related gastroenterology studies
- Cancer, Lipids, and Metabolism
- Cancer-related molecular mechanisms research
- Cancer Immunotherapy and Biomarkers
- Viral gastroenteritis research and epidemiology
- Cancer, Hypoxia, and Metabolism
- Diet and metabolism studies
- Clostridium difficile and Clostridium perfringens research
- Bacterial Genetics and Biotechnology
- Cancer Cells and Metastasis
- Mycobacterium research and diagnosis
- Probiotics and Fermented Foods
- Metabolism, Diabetes, and Cancer
- Heat shock proteins research
- Ferroptosis and cancer prognosis
- Microscopic Colitis
- MicroRNA in disease regulation
Tulane University
2015-2024
NorthShore University HealthSystem
2009-2013
Evanston Hospital
2011
University Gastroenterology
2010
Western Research Institute
2008
Jesse Brown VA Medical Center
1997-2005
University of Illinois Chicago
1996-2004
Argonne National Laboratory
1996
The initial response to infection is recruitment of acute inflammatory cells the involved site. Interleukin (IL)-8 prototypical effector molecule for this process. Transcription IL-8 gene primarily governed by nuclear transcription factor (NF)-κB. Intestinal epithelial produce in enteric pathogens yet remain quiescent a milieu where they are literally bathed normal bacterial flora. We therefore sought investigate NF-κB activation enteropathogenic Escherichia coli (EPEC), nonpathogenic E....
An intense inflammatory cell infiltrate, consisting primarily of polymorphonuclear leukocytes (PMN), accompanies enteric infection by enteropathogenic Escherichia coli (EPEC). The mechanism(s) which this pathogen elicits PMN recruitment has not been studied. To determine whether EPEC intestinal epithelial cells induces to transmigrate, an in vitro model cultured human monolayers (T84), a strain (E2348/69), and isolated was used. Results these studies showed that attachment T84 stimulated the...
Soy consumption is associated with a lower incidence of colon cancer which believed to be mediated by one its components, genistein. Genistein may inhibit progression inducing apoptosis or inhibiting proliferation, but mechanisms are not well understood. Epidermal growth factor (EGF)-induced proliferation cells plays an important role in and loss tumor suppressor FOXO3 activity. The aim this study was assess if genistein exerts anti-proliferative properties attenuating the negative effect...
Abstract Desmoplastic small round cell tumors (DSRCT) are a type of aggressive, pediatric sarcoma characterized by the EWSR1::WT1 fusion oncogene. Targeted therapies for DSRCT have not been developed, and standard multimodal therapy is insufficient, leading to 5-year survival rate only 15% 25%. Here, we depleted in established its essentiality vivo. Transcriptomic analysis revealed that induces unique transcriptional alterations compared with WT1 other oncoproteins binding directly mediates...
ABSTRACT Enteropathogenic Escherichia coli (EPEC) is an important cause of diarrhea in humans. EPEC infection cultured intestinal epithelial cells induces attaching and effacing (A/E) lesions, alters ion transport, increases paracellular permeability, stimulates inflammation. The lack a small-animal model has restricted vivo studies examining EPEC-host interactions. aim this study was to characterize the C57BL/6J mouse as infection. We have shown that can adhere colonize epithelium mice....
Enteropathogenic Escherichia coli (EPEC) alters many functions of the host intestinal epithelia. Inflammation is initiated by activation nuclear factor (NF)-κB, and paracellular permeability enhanced via a Ca 2+ - myosin light-chain kinase (MLCK)-dependent pathway. The aims this study were to identify signaling pathways which EPEC triggers inflammation determine whether these parallel or diverge from those that alter permeability. EPEC-induced phosphorylation degradation primary inhibitor...
We showed previously that enteropathogenic Escherichia coli (EPEC) infection of intestinal epithelial cells induces inflammation by activating NF-κB and upregulating IL-8 expression. also reported extracellular signal-regulated kinases (ERKs) participate in EPEC-induced activation but other signaling molecules such as PKCζ may be involved. The aim this study was to determine whether is activated EPEC investigate it plays a role EPEC-associated inflammation. induced the translocation from...
Enteric bacteria and their products play an important role in intestinal inflammation; however, the complete mechanisms are not elucidated yet. Tumor suppressor Foxo3a regulates gene expression nucleus, its translocation to cytosol leads inactivation. Proximally, is regulated by different pathways including phosphoinositide 3-kinase (PI3K) pathway. The aim of this study was determine effect bacterial infection on epithelial cells examine contribution inflammation. Bacterial...
Obesity, an immense epidemic affecting approximately half a billion adults, has doubled in prevalence the last several decades. Epidemiological data support that obesity, due to intake of high-fat, western diet, increases risk colon cancer; however, mechanisms underlying this remain unclear. Here, utilizing next generation RNA sequencing, we aimed determine high-fat diet (HFD) mediated expression profile mouse and azoxymethane/dextran sulfate sodium model cancer. Mice on HFD had...
Intestinal inflammation is associated with low levels of mucosal ATP, highlighting the importance mitochondrial function ATP production in pathophysiology disease. In inflamed colon humans and mice, we found decreased complex cytochrome c oxidase I/IV lower levels. Thus, generated colonic ρ0 cells reduced linked to by selective depletion DNA. these cells, RNA sequencing revealed a substantial number differentially expressed transcripts, among which 240 belonged inflammatory pathways...
Hydrogels serve as three-dimensional scaffolds whose composition can be customized to allow attachment and proliferation of several different cell types. Extracellular matrix-derived hydrogels are considered close replicates the tissue microenvironment. They for in vitro engineering a useful tool study cell-scaffold interaction. The aim present was analyze effect adipose-derived stromal/stem cells (ASCs) decellularized adipose tissue-derived (DAT) hydrogel interaction on ASC morphology,...
Background & AimsDiminished forkhead box O3 (FOXO3) function drives inflammation and cancer growth; however, mechanisms fostering these pathobiologies are unclear. Here, we aimed to identify in colon loss of FOXO3-dependent cellular molecular changes that facilitate inflammation-mediated tumor growth.MethodsFOXO3 knockout (KO) wild-type (WT) mice were used the AOM/DSS model cancer. Bioinformatics for profiling mRNA sequencing data from human mouse tumors; specific targets validated cells...
Abstract The heterogeneous pathobiology underlying Ulcerative Colitis (UC) is not fully understood. Using publicly available transcriptomes from adult UC patients, we identified the immune cell landscape, molecular pathways, and differentially expressed genes (DEGs) across patient cohorts their association with treatment outcomes. global landscape of tissue included increased neutrophils, T CD4 memory activated cells, active dendritic cells (DC), M0 macrophages, as well reduced trends in...
Abstract Obesity is a worldwide epidemic associated with increased risk and progression of colon cancer. Here, we aimed to determine the role adipose triglyceride lipase (ATGL), responsible for intracellular lipid droplet (LD) utilization, in obesity-driven colonic tumorigenesis. In local cancer patients, significantly ATGL levels tumor tissue, compared controls, were augmented obese individuals. Elevated human cells (CCC) relative non-transformed by an obesity mediator, oleic acid (OA). CCC...
Epithelial proliferation, critical for homeostasis, healing, and colon cancer progression, is in part controlled by epidermal growth factor receptor (EGFR). Proliferation of colonic epithelia can be induced Citrobacter rodentium infection, we have demonstrated that activity tumor suppressor FOXO3 was attenuated after this infection. Thus the aim study to determine contribution EGFR-dependent proliferation intestinal cell lines. In show that, during infection with C. rodentium, EGFR...
Intestinal inflammation has been recently characterized by the dysregulation of lipids as metabolic and energy sources, revealing a novel feature its pathophysiology. Because intracellular lipids, stored in dynamic lipid droplets (LDs), provide for cellular needs, we investigated whether they play role intestinal inflammation. In inflamed intestine mice, elevated LDs were found colonic infiltrating immune cells shown staining LD coat protein PLIN2 with BODIPY. cells, TNF stimulated increases...
Inflammatory bowel disease (IBD), characterized by infiltration of polymorphonuclear neutrophils (PMNs), increases the risk colon cancer. PMN activation corresponds to accumulation intracellular Lipid Droplets (LDs). As increased LDs are negatively regulated transcription factor Forkhead Box O3 (FOXO3), we aim determine significance this regulatory network in PMN-mediated IBD and tumorigenesis. Affected tissue cancer patients, colonic infiltrated immune cells, have LDs' coat protein, PLIN2....
Head and neck squamous cell carcinoma (HNSCC) is a major cause of morbidity mortality underscoring the need for safe effective chemopreventive strategies. Targeting epidermal growth factor receptor (EGFR) attractive in that it an early critical event HNSCC pathogenesis. However, current agents lack efficacy or have unacceptable toxicity. Several groups demonstrated over-the-counter medication, polyethylene glycol (PEG) has remarkable against colon carcinogenesis. Importantly, we reported...
Obesity, characterized by augmented inflammation and tumorigenesis, is linked to genetic predispositions, such as FOXO3 polymorphisms. As obesity associated with aberrant macrophages infiltrating different tissues, including the colon, we aimed identify FOXO3-dependent transcriptomic changes in that drive obesity-mediated colonic tumorigenesis. We found mouse high-fat-diet-(HFD)-related led diminished levels increased macrophages. Transcriptomic analysis of peritoneal FOXO3-deficient showed...
Inflammatory bowel disease (IBD) has been linked to active signaling with bacterial components and reduced mitochondrial ATP production; however, synergism between both of these characteristics remains unclear. We aimed determine in human IBD transcriptomes the link a transcriptional signature unique intestinal cells (ICs) production (Mito-0) bacteria triggered using bioinformatics approach. generated an IC Mito-0 panel comprised 199 differentially expressed (DE) transcripts mediated by...