A5090856781- Single-cell and spatial transcriptomics
- Cancer Cells and Metastasis
- Genetic factors in colorectal cancer
- Gut microbiota and health
- Cancer Genomics and Diagnostics
- Helicobacter pylori-related gastroenterology studies
- Inflammatory Bowel Disease
- Innovative Microfluidic and Catalytic Techniques Innovation
- Colorectal Cancer Treatments and Studies
- Microscopic Colitis
- IL-33, ST2, and ILC Pathways
- Bacteriophages and microbial interactions
- CRISPR and Genetic Engineering
- Immune cells in cancer
- Epigenetics and DNA Methylation
- Cell Image Analysis Techniques
- Digestive system and related health
- AI in cancer detection
- Molecular Biology Techniques and Applications
- Pancreatic and Hepatic Oncology Research
- NF-κB Signaling Pathways
- Cancer Immunotherapy and Biomarkers
- Global Healthcare and Medical Tourism
- Colorectal and Anal Carcinomas
- Ferroptosis and cancer prognosis
Vanderbilt University
2019-2025
Vanderbilt University Medical Center
2019-2024
Universidad de Valladolid
2002
Colorectal cancers (CRCs) arise from precursor polyps whose cellular origins, molecular heterogeneity, and immunogenic potential may reveal diagnostic therapeutic insights when analyzed at high resolution. We present a single-cell transcriptomic imaging atlas of the two most common human colorectal polyps, conventional adenomas serrated their resulting CRC counterparts. Integrative analysis 128 datasets 62 participants reveals WNT-driven expansion stem cells, while derive differentiated...
Colorectal cancer exhibits dynamic cellular and genetic heterogeneity during progression from precursor lesions toward malignancy. Analysis of spatial multi-omic data 31 human colorectal specimens enabled phylogeographic mapping tumor evolution that revealed individualized trajectories accompanying microenvironmental clonal alterations. Phylogeographic ordered events, classified tumors by their evolutionary dynamics, placed regions along global pseudotemporal encompassing the chromosomal...
Crohn's disease (CD) is a complex chronic inflammatory disorder with both gastrointestinal and extra-intestinal manifestations associated immune dysregulation. Analyzing 202,359 cells from 170 specimens across 83 patients, we identify distinct epithelial cell type in terminal ileum ascending colon (hereon as 'LND') high expression of LCN2, NOS2, DUOX2 genes related to antimicrobial response immunoregulation. LND cells, confirmed by in-situ RNA protein imaging, are rare non-IBD controls but...
Abstract Increasingly, highly multiplexed tissue imaging methods are used to profile protein expression at the single‐cell level. However, a critical limitation is lack of robust cell segmentation tools for sections. We present Multiplexed Image Resegmentation Internal Aberrant Membranes (MIRIAM) that combines (a) pipeline and quantification incorporates machine learning‐based pixel classification define cellular compartments, (b) novel method extending incomplete membranes, (c) deep shape...
The structure and function of the mammalian gut vary by region, yet why inflammatory diseases manifest in specific regions not others remains unclear. We use a TNF–overexpressing Crohn′s disease (CD) model (Tnf ΔARE/+ ), which typically presents terminal ileum (TI), to investigate how environmental factors interact with host′s immune susceptibility drive region–specific disease. identified Chlamydia muridarum , an intracellular bacterium murine counterpart human sexually transmitted C....
Abstract Dysplasia is considered a key transition state between pre-cancer and cancer in gastric carcinogenesis. However, the cellular or phenotypic heterogeneity mechanisms of dysplasia progression have not been elucidated. We established metaplastic dysplastic organoid lines, derived from Mist1-Kras(G12D) mouse stomach corpus studied distinct behaviors characteristics organoids. also examined functional roles for Kras activation using Selumetinib, MEK inhibitor, which downstream mediator...
Anti-tumor necrosis factor (anti-TNF) therapy resistance is a major clinical challenge in inflammatory bowel disease (IBD), due, part, to insufficient understanding of disease-site, protein-level mechanisms. Although proteomics data from IBD mouse models exist, and phenotype discrepancies contribute confounding translation preclinical animal cohorts. We developed an approach called translatable components regression (TransComp-R) overcome interspecies trans-omic between human subjects....
The increasing demand of single-cell RNA-sequencing (scRNA-seq) experiments, such as the number experiments and cells queried per experiment, necessitates higher sequencing depth coupled to high data quality. New high-throughput sequencers, Illumina NovaSeq 6000, enables this be filled in a cost-effective manner. However, current scRNA-seq library designs present compatibility challenges with newer technologies, index-hopping, their ability generate quality has yet systematically evaluated....
The tumor microenvironment plays a key role in the pathogenesis of colorectal tumors and contains various cell types including epithelial, immune, mesenchymal cells. Characterization interactions between these is necessary for revealing complex nature tumors. In this study, we used single-cell RNA-seq (scRNA-seq) to compare microenvironments mouse model sporadic adenoma (Lrig1 CreERT2/+ ;Apc 2lox14/+ ) inflammation-driven cancer induced by azoxymethane dextran sodium sulfate (AOM/DSS). While...
Aberrant epithelial differentiation and regeneration contribute to colon pathologies, including inflammatory bowel disease (IBD) colitis-associated cancer (CAC). Myeloid translocation gene 16 (MTG16, also known as CBFA2T3) is a transcriptional corepressor expressed in the colonic epithelium. MTG16 deficiency mice exacerbates colitis increases tumor burden CAC, though underlying mechanisms remain unclear. Here, we identified central mediator of differentiation, promoting goblet restraining...
Crohn's disease (CD) is a complex chronic inflammatory disorder that may affect any part of gastrointestinal tract with extra-intestinal manifestations and associated immune dysregulation. To characterize heterogeneity in CD, we profiled single-cell transcriptomics 170 samples from 65 CD patients 18 non-inflammatory bowel (IBD) controls both the terminal ileum (TI) ascending colon (AC). Analysis 202,359 cells identified novel epithelial cell type TI AC, featuring high expression
Abstract Microbial influences on host cells depend upon the identities of microbes, their spatial localization, and responses they invoke specific cell populations. Multimodal analyses both microbes in a spatially resolved fashion would enable studies into these complex interactions native tissue environments, potentially clinical specimens. While techniques to preserve each microbial compartments have been used examine tissues separately, we endeavored develop approaches simultaneously...
Colorectal cancer exhibits dynamic cellular and genetic heterogeneity during progression from precursor lesions toward malignancy. Leveraging spatial molecular information to construct a phylogeographic map of tumor evolution can reveal individualized growth trajectories with diagnostic therapeutic potential. Integrative analysis multi-omic data 31 colorectal specimens revealed simultaneous microenvironmental clonal alterations as function progression. Copy number variation served...
Abstract Increasingly, highly multiplexed in situ tissue imaging methods are used to profile protein expression at the single-cell level. However, a critical limitation is lack of robust cell segmentation tools applicable for sections tissues with complex architecture and multiple types. Using human colorectal adenomas, we present pipeline quantification that utilizes machine learning-based pixel classification define cellular compartments, novel method extending incomplete membranes,...
This paper proposes a new fault detection and diagnosis (FDD) method based on the online parameter estimation using frequency contents of signals backpropagation neural networks. When occurs parameters in nonlinear mathematical model process change. A for detecting tracking different values is proposed, which tries to be robust with respect low disturbances. The FDD together classical are applied wastewater treatment plant, placed Manresa, Spain. set real experiments presented order compare...
Abstract BACKGROUND The majority of Crohn’s disease patients present with ileitis or ileocolitis, however, the factors that drive development inflammation in these different sites remain elusive. TnfΔARE mouse model recapitulates many features and is driven by systemic overexpression TNF. AIMS To-date, published as a spontaneous intestinal specific to ileum, we observe severe colonic dependent on murine housing facility. We aimed use experimental approaches investigate epithelial microbial...
Abstract Aberrant epithelial differentiation and regeneration contribute to colon pathologies including inflammatory bowel disease (IBD) colitis-associated cancer (CAC). MTG16 (CBFA2T3) is a transcriptional corepressor expressed in the colonic epithelium. deficiency mice exacerbates colitis increases tumor burden CAC, though underlying mechanisms remain unclear. Here, we identified as central mediator of differentiation, promoting goblet restraining enteroendocrine cell development...
Inflammatory Bowel Disease (IBD) and its subtype Crohn’s disease (CD) arise due to a loss of tolerance environmental antigens in genetically susceptible individuals. Longitudinal analysis CD incidence has identified an inverse correlation between rates communicable autoimmune disorders, particularly countries endemic for helminth infestation. A case report published by Broadhurst et al described the use eggs treat IBD patient with refractory disease. Induction type 2 immune response...
Cellular heterogeneity in cancer development is considered as a source of cell generation and drug resistance. However, cellular has not been fully eluciated during metaplasia progression to gastric pre-neoplasia neoplasia carcinogenesis. Recent investigations have suggested that Ras activation, rather than mutation, may promote the We recently established several vitro metaplastic/pre-neoplastic organoid lines; Meta3-metaplasia Meta4-pre-neoplasia, derived from mouse stomachs induced active...