A5076831810- Cancer Research and Treatments
- Genetic factors in colorectal cancer
- Colorectal Cancer Treatments and Studies
- Cancer Immunotherapy and Biomarkers
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Gut microbiota and health
- Cancer Genomics and Diagnostics
- Polyamine Metabolism and Applications
- Molecular Biology Techniques and Applications
- Clostridium difficile and Clostridium perfringens research
- Cannabis and Cannabinoid Research
- Prostate Cancer Treatment and Research
- Mycobacterium research and diagnosis
- Amino Acid Enzymes and Metabolism
- Histone Deacetylase Inhibitors Research
- Ubiquitin and proteasome pathways
- Immune cells in cancer
- Carcinogens and Genotoxicity Assessment
- Cancer-related gene regulation
- Cancer-related molecular mechanisms research
- Colorectal and Anal Carcinomas
- PARP inhibition in cancer therapy
- Helicobacter pylori-related gastroenterology studies
- Microscopic Colitis
Johns Hopkins University
2011-2023
Sidney Kimmel Comprehensive Cancer Center
2013-2023
Johns Hopkins Medicine
2016-2023
Bloomberg (United States)
2016-2018
University of Baltimore
2010
University of California, Davis
2008-2009
Individuals with sporadic colorectal cancer (CRC) frequently harbor abnormalities in the composition of gut microbiome; however, microbiota associated precancerous lesions hereditary CRC remains largely unknown. We studied colonic mucosa patients familial adenomatous polyposis (FAP), who develop benign precursor (polyps) early life. identified patchy bacterial biofilms composed predominately
It is estimated that the etiology of 20–30% epithelial cancers directly associated with inflammation, although direct molecular events linking inflammation and carcinogenesis are poorly defined. In context gastrointestinal disease, bacterium enterotoxigenic Bacteroides fragilis (ETBF) a significant source chronic has been implicated as risk factor for colorectal cancer. Spermine oxidase (SMO) polyamine catabolic enzyme highly inducible by inflammatory stimuli resulting in increased reactive...
Colorectal cancer is multifaceted, with subtypes defined by genetic, histologic, and immunologic features that are potentially influenced inflammation, mutagens, and/or microbiota. cancers activating mutations in BRAF associated distinct clinical characteristics, although the pathogenesis not well understood. The Wnt-driven multiple intestinal neoplasia (MinApcΔ716/+) enterotoxigenic Bacteroides fragilis (ETBF) murine model characterized IL17-dependent, distal colon adenomas. Herein, we...
Background. Chronic inflammation and composition of the colon microbiota have been associated with colorectal cancer in humans. The human commensal enterotoxigenic Bacteroides fragilis (ETBF) is linked to both inflammatory bowel disease and, our murine model, causes interleukin 17A (IL-17A)–dependent tumors. In these studies, we hypothesized that persistent colonization by ETBF required for tumorigenesis. Methods. We established a method clearing mice, using antibiotic cefoxitin. Multiple...
Abstract Aberrant silencing of genes by DNA methylation contributes to cancer, yet how this process is initiated remains unclear. Using a murine model inflammation-induced tumorigenesis, we tested the hypothesis that inflammation promotes recruitment epigenetic proteins chromatin, initiating and gene in tumors. Compared with normal epithelium noninflammation-induced tumors, tumors gained at CpG islands, some which are associated putative tumor suppressor genes. Hypermethylated exhibited...
Polyamines have been implicated in numerous biological processes, including inflammation and carcinogenesis. Homeostatic regulation leads to interconversion of the polyamines putrescine, downstream metabolites spermidine spermine. The enzyme spermine oxidase (SMOX), which back-converts spermidine, contributes polyamine levels, but can also other effects. We SMOX gastric carcinogenesis due infection by pathogen Helicobacter pylori. Additionally, we reported that be upregulated humans with...
Cisplatin-induced nephrotoxicity limits its use in many cancer patients. The expression of enzymes involved polyamine catabolism, spermidine/spermine N1-acetyltransferase (SSAT) and spermine oxidase (SMOX) increase the kidneys mice treated with cisplatin. We hypothesized that enhanced catabolism contributes to tissue damage cisplatin acute kidney injury (AKI). Using gene knockout chemical inhibitors, role AKI was examined. Deficiency SSAT, SMOX or neutralization toxic products degradation,...
Naphthalene is a volatile hydrocarbon that causes dose-, species-, and cell type-dependent cytotoxicity after acute exposure hyperplasia/neoplasia lifetime exposures in rodents. Toxicity depends on metabolic activation, reactive metabolite binding correlates with tissue site susceptibility.We compared proteins adducted nasal epithelium from rats rhesus macaques vitro.Adducted recovered incubations of 14C-naphthalene were separated by two-dimensional (2D) gel electrophoresis imaged to...
Pro-carcinogenic bacteria have the potential to initiate and/or promote human colon cancer. However, mechanism(s) by which a bacterium may trigger carcinogenesis remains unclear. Herein, we show Bacteroides fragilis toxin (BFT) secretion pathobiont enterotoxigenic (ETBF) triggers in Min Apc /- mice ETBF pro- carcinogenic inflammatory cascade requiring IL-17R, NF-κB, and Stat3 signaling colonic epithelial cells (CEC). This promotes chemokine-dependent recruitment of pro-tumoral myeloid cells....
Abstract Background Polyamine catabolism plays a key role in maintaining intracellular polyamine pools, yet its physiological significance is largely unexplored. Here, we report that the disruption of leads to severe cerebellar damage and ataxia, demonstrating fundamental maintenance function integrity. Methods Mice with simultaneous deletion two principal catabolic enzymes, spermine oxidase spermidine/spermine N 1 -acetyltransferase ( Smox / Sat1 -dKO), were generated by crossbreeding -KO −...
A limited number of cell lines have fueled the majority preclinical prostate cancer research, but their genomes remain incompletely characterized. Here, we utilized whole-genome linked-read sequencing for comprehensive characterization phased mutations and rearrangements in most commonly used research including PC3, LNCaP, DU145, CWR22Rv1, VCaP, LAPC4, MDA-PCa-2b, RWPE-1, four derivative castrate-resistant (CR) LNCaP_Abl, LNCaP_C42b, VCaP-CR, LAPC4-CR. Phasing allowed determination...
Abstract It is estimated that the etiology of 20-30% epithelial cancers directly associated with inflammation, though molecular events linking inflammation and necessary carcinogenic mutations remain to be clarified. In context gastrointestinal disease, bacterial pathogens Helicobacter pylori enterotoxigenic Bacteroides fragilis (ETBF) are significant sources chronic have been implicated as risk factors for development gastric colorectal cancer, respectively. We previously demonstrated H....
Sporadic colorectal cancer (CRC) remains a global health burden with rising incidence in younger patients (<50 years), enhancing the need to identify novel targets for diagnosis and treatment. Certain T cell subsets appear be associated CRC prognosis; Th1 subsets, marked by interferon gamma (IFNγ), better prognoses, Th17, interleukin‐17 (IL‐17), worse prognoses. Several studies have shown that Fusobacteria (Fuso), specifically Fusobacterium nucleatum (Fn), are prevalent tissues despite...
<div>Abstract<p>Aberrant silencing of genes by DNA methylation contributes to cancer, yet how this process is initiated remains unclear. Using a murine model inflammation-induced tumorigenesis, we tested the hypothesis that inflammation promotes recruitment epigenetic proteins chromatin, initiating and gene in tumors. Compared with normal epithelium noninflammation-induced tumors, tumors gained at CpG islands, some which are associated putative tumor suppressor genes....
<p>Supplemental Methods for the MBD-seq analysis and Table S1, which provides primer sequences assays used Taqman pyrosequencing.</p>
<p>Figure S1 provides additional analysis of DMRs, including genic location, bivalent status, methylation validation, and IPA analysis. Figure S2 evidence supporting the finding that oxidative damage-induced gene expression changes occur in epithelial cells. S3 demonstrates inflammatory response to ETBF is similar WT Msh2 deficient mice. S4 Min mice have higher CFU/g their stool than S5 DNA validation for MBD-seq data presented 5.</p>
<p>Process gene ontologies with significant enrichment in the sets differential methylation.</p>