Contact

  • Academic
    ceguo@stanford.edu
    University - Scholar Department: Surgery Position: Medical Fellow

All Publications

  • NFAT mediates pro-tumorigenic inflammation in cancer-associated fibroblasts in pancreatic ductal adenocarcinoma. Cell reports Guo, C., Griffin, M. F., Morgan, A. G., Foster, D. S., Parker, J. B., Januszyk, M., Lindsay, H. G., Guardino, N. J., Reveron-Thornton, R., Xie, P. Y., Valencia, C., Kuhnert, M. M., Korah, M., Gonçalves, A., Guo, J. L., Delitto, A. E., Agolia, J. P., Tabora, A. D., Dua, M. M., Visser, B. C., Poultsides, G. A., Delitto, D., Longaker, M. T., Norton, J. A. 2026; 45 (1): 116849

    Abstract

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense stroma, low immunogenicity, and resistance to therapy. Cancer-associated fibroblasts (CAFs) are key stromal cells within the tumor microenvironment (TME) that drive tumor progression. Interleukin-1 (IL-1) promotes fibrosis, pathogenic inflammation, and poor prognosis in PDAC. Using a single-cell multi-omic approach, we investigate the IL-1 signaling axis in human and mouse models of PDAC, identifying nuclear factor of activated T cells (NFAT) transcription factors as key mediators. IL1R1+ CAFs activate an inflammatory phenotype associated with elevated NFAT motif activity and gene expression. In vivo, NFAT inhibition in a mouse model of PDAC significantly reduces tumor weight and fibrosis, supporting its pro-tumorigenic role. Our findings suggest that NFAT mediates IL-1-induced inflammation in PDAC, highlighting its potential as a therapeutic target. This study demonstrates the power of multi-omic analyses to uncover therapeutic targets within the complex TME.

    View details for DOI 10.1016/j.celrep.2025.116849

    View details for PubMedID 41533513

  • Protocol for orthotopic implantation of a collagen hydrogel to model pancreatic ductal adenocarcinoma in mice. STAR protocols Agolia, J. P., Xie, P. Y., Korah, M., Fallah, M., Reveron-Thornton, R. F., Guo, C., Reddy, B., Sivasubramanian, R., Longaker, M. T., Chaudhuri, O., Foster, D. S., Delitto, D. 2026; 7 (1): 104337

    Abstract

    Available mouse models for pancreatic ductal adenocarcinoma (PDAC) are limited by slow tumor development and failure to recapitulate key stromal and immune characteristics. Here, we present a protocol for generating a collagen hydrogel mouse model for orthotopic PDAC. We describe steps for embedding mouse pancreatic cancer cells in a dense collagen hydrogel and surgically implanting it into the mouse pancreas. Mouse PDAC tumors typically reach 1 cm in diameter by 10 days after implantation and show immune and stromal cell recruitment. For complete details on the use and execution of this protocol, please refer to Korah et al.1.

    View details for DOI 10.1016/j.xpro.2025.104337

    View details for PubMedID 41533505

  • Disruption of fibroblast MYD88 signaling promotes antitumor immunity in pancreatic ductal adenocarcinoma. Cell reports Korah, M., Reveron-Thornton, R. F., Fallah, M., Xie, P. Y., Gonçalves, A., Guo, C., Agolia, J. P., Delitto, A. E., Flojo, R. A., Reddy, B., Yip, K. A., Lu, J. M., Tomasso, A., Tabora, A. D., Guo, J. L., Bauer-Rowe, K. E., Pham, B., Goyal, L., Kirane, A. R., Charville, G. W., Chaudhuri, O., Dua, M. M., Visser, B. C., Lee, B., Poultsides, G. A., Wan, D. C., Norton, J. A., Foster, D. S., Longaker, M. T., Delitto, D. 2025; 44 (10): 116347

    Abstract

    Pancreatic ductal adenocarcinoma (PDAC) continues to carry a dismal prognosis. The disease is characterized by a uniquely dense fibrotic matrix generated by cancer-associated fibroblasts (CAFs). We have previously demonstrated that fibroblast-driven chronic inflammation suppresses T cell function through a myeloid differentiation primary response protein 88 (MYD88)-dependent mechanism. While extensively studied in myeloid cells, the role of MYD88 signaling in CAFs and its effects on PDAC remain poorly understood. In this study, we identify a MYD88-driven inflammatory CAF population in PDAC using a combination of bulk, single-cell, and spatial transcriptomic studies. Using an innovative collagen gel implantation model, we demonstrate that loss of MYD88 in CAFs enhances T cell infiltration and suppresses tumor growth. Combining MYD88 inhibition with immune checkpoint blockade significantly reduces tumor size and enhances antitumor immune responses, underscoring its potential as a therapeutic target in PDAC.

    View details for DOI 10.1016/j.celrep.2025.116347

    View details for PubMedID 41004339

  • Simultaneous Multiomic Single-Cell Analysis Reveals Gene Regulatory Mechanism of Interleukin-Based Immunotherapy in Pancreatic Ductal Adenocarcinoma Guo, C., Morgan, A., Griffin, M., Parker, J. B. L., Januszyk, M., Foster, D., Delitto, D., Longaker, M. T., Norton, J. A. LIPPINCOTT WILLIAMS & WILKINS. 2024: S456

    View details for Web of Science ID 001348680703113

  • Organoid Assessment of IL-1 Inhibition in Human Pancreatic Ductal Adenocarcinoma Morgan, A., Griffin, M., Guo, C., Parker, J. B. L., Januszyk, M., Foster, D. S., Poultsides, G. A., Delitto, D., Longaker, M. T., Norton, J. A. LIPPINCOTT WILLIAMS & WILKINS. 2024: S451-S452

    View details for Web of Science ID 001348680703104

  • Self-Reporting Transposons Enable Simultaneous Readout of Gene Expression and Transcription Factor Binding in Single Cells CELL Moudgil, A., Wilkinson, M. N., Chen, X., He, J., Cammack, A. J., Vasek, M. J., Lagunas, T., Qi, Z., Lalli, M. A., Guo, C., Morris, S. A., Dougherty, J. D., Mitra, R. D. 2020; 182 (4): 992-+

    Abstract

    Cellular heterogeneity confounds in situ assays of transcription factor (TF) binding. Single-cell RNA sequencing (scRNA-seq) deconvolves cell types from gene expression, but no technology links cell identity to TF binding sites (TFBS) in those cell types. We present self-reporting transposons (SRTs) and use them in single-cell calling cards (scCC), a novel assay for simultaneously measuring gene expression and mapping TFBS in single cells. The genomic locations of SRTs are recovered from mRNA, and SRTs deposited by exogenous, TF-transposase fusions can be used to map TFBS. We then present scCC, which map SRTs from scRNA-seq libraries, simultaneously identifying cell types and TFBS in those same cells. We benchmark multiple TFs with this technique. Next, we use scCC to discover BRD4-mediated cell-state transitions in K562 cells. Finally, we map BRD4 binding sites in the mouse cortex at single-cell resolution, establishing a new method for studying TF biology in situ.

    View details for DOI 10.1016/j.cell.2020.06.037

    View details for Web of Science ID 000561488500018

    View details for PubMedID 32710817

    View details for PubMedCentralID PMC7510185

  • CellTag Indexing: genetic barcode-based sample multiplexing for single-cell genomics. Genome biology Guo, C., Kong, W., Kamimoto, K., Rivera-Gonzalez, G. C., Yang, X., Kirita, Y., Morris, S. A. 2019; 20 (1): 90

    Abstract

    High-throughput single-cell assays increasingly require special consideration in experimental design, sample multiplexing, batch effect removal, and data interpretation. Here, we describe a lentiviral barcode-based multiplexing approach, CellTag Indexing, which uses predefined genetic barcodes that are heritable, enabling cell populations to be tagged, pooled, and tracked over time in the same experimental replicate. We demonstrate the utility of CellTag Indexing by sequencing transcriptomes using a variety of cell types, including long-term tracking of cell engraftment and differentiation in vivo. Together, this presents CellTag Indexing as a broadly applicable genetic multiplexing tool that is complementary with existing single-cell technologies.

    View details for DOI 10.1186/s13059-019-1699-y

    View details for PubMedID 31072405

    View details for PubMedCentralID PMC6509836

  • Single-cell mapping of lineage and identity in direct reprogramming. Nature Biddy, B. A., Kong, W., Kamimoto, K., Guo, C., Waye, S. E., Sun, T., Morris, S. A. 2018; 564 (7735): 219-224

    Abstract

    Direct lineage reprogramming involves the conversion of cellular identity. Single-cell technologies are useful for deconstructing the considerable heterogeneity that emerges during lineage conversion. However, lineage relationships are typically lost during cell processing, complicating trajectory reconstruction. Here we present 'CellTagging', a combinatorial cell-indexing methodology that enables parallel capture of clonal history and cell identity, in which sequential rounds of cell labelling enable the construction of multi-level lineage trees. CellTagging and longitudinal tracking of fibroblast to induced endoderm progenitor reprogramming reveals two distinct trajectories: one leading to successfully reprogrammed cells, and one leading to a 'dead-end' state, paths determined in the earliest stages of lineage conversion. We find that expression of a putative methyltransferase, Mettl7a1, is associated with the successful reprogramming trajectory; adding Mettl7a1 to the reprogramming cocktail increases the yield of induced endoderm progenitors. Together, these results demonstrate the utility of our lineage-tracing method for revealing the dynamics of direct reprogramming.

    View details for DOI 10.1038/s41586-018-0744-4

    View details for PubMedID 30518857

    View details for PubMedCentralID PMC6635140

  • Engineering cell identity: establishing new gene regulatory and chromatin landscapes. Current opinion in genetics & development Guo, C., Morris, S. A. 2017; 46: 50-57

    Abstract

    Cellular reprogramming can be achieved by ectopically expressing transcription factors that directly convert one differentiated cell type into another, bypassing embryonic states. A number of different cell types have been generated by such 'direct lineage reprogramming' methods, but their practical utility has been limited because, in most protocols, the resulting populations are often partially differentiated or incompletely specified. Here, we review mechanisms of lineage reprogramming by pioneer transcription factors, a unique class of transcriptional regulators that has the capacity to engage with silent chromatin to activate target gene regulatory networks. We assess the possible barriers to successful reprogramming in the context of higher-order chromatin landscape, considering how the mechanistic relationship between nuclear organization and cell identity will be crucial to unlocking the full potential of cell fate engineering.

    View details for DOI 10.1016/j.gde.2017.06.011

    View details for PubMedID 28667865

  • Cardiomyocyte-specific role of miR-24 in promoting cell survival. Journal of cellular and molecular medicine Guo, C., Deng, Y., Liu, J., Qian, L. 2015; 19 (1): 103-12

    Abstract

    Cardiomyocyte cell death is a major contributing factor to various cardiovascular diseases and is therefore an important target for the design of therapeutic strategies. More recently, stem cell therapies, such as transplantation of embryonic or induced pluripotent stem (iPS) cell-derived cardiomyocytes, have emerged as a promising alternative therapeutic avenue to treating cardiovascular diseases. Nevertheless, survival of these introduced cells is a serious issue that must be solved before clinical application. We and others have identified a small non-coding RNA, microRNA-24 (miR-24), as a pro-survival molecule that inhibits the apoptosis of cardiomyocytes. However, these earlier studies delivered mimics or inhibitors of miR-24 via viral transduction or chemical transfection, where the observed protective role of miR-24 in cardiomyocytes might have partially resulted from its effect on non-cardiomyocyte cells. To elucidate the cardiomyocyte-specific effects of miR-24 when overexpressed, we developed a genetic model by generating a transgenic mouse line, where miR-24 expression is driven by the cardiac-specific Myh6 promoter. The Myh6-miR-24 transgenic mice did not exhibit apparent difference from their wild-type littermates under normal physiological conditions. However, when the mice were subject to myocardial infarction (MI), the transgenic mice exhibited decreased cardiomyocyte apoptosis, improved cardiac function and reduced scar size post-MI compared to their wild-type littermates. Interestingly, the protective effects observed in our transgenic mice were smaller than those from earlier reported approaches as well as our parallelly performed non-genetic approach, raising the possibility that non-genetic approaches of introducing miR-24 might have been mediated via other cell types than cardiomyocytes, leading to a more dramatic phenotype. In conclusion, our study for the first time directly tests the cardiomyocyte-specific role of miR-24 in the adult heart, and may provide insight to strategy design when considering miRNA-based therapies for cardiovascular diseases.

    View details for DOI 10.1111/jcmm.12393

    View details for PubMedID 25352422

    View details for PubMedCentralID PMC4288354

  • Direct Somatic Cell Reprogramming: Treatment of Cardiac Diseases CURRENT GENE THERAPY Guo, C., Patel, K., Qian, L. 2013; 13 (2): 133-138

    Abstract

    Cardiac diseases are the major causes of morbidity and mortality in the world. Cardiomyocyte death is a common consequence of many types of heart diseases and is usually irreversible. Scar tissues formed by cardiac fibroblasts serve compensatory roles for the injured heart but eventually weaken cardiac function and result in life-threatening heart failures. Unfortunately, adult human hearts have limited regenerative capacities. In the past decades, many interventional approaches have been taken in an attempt to restore functional cardiomyocytes in an injured heart. Promising advances have been made in directly reprogramming mouse fibroblasts into cardiomyocyte-like cells both in vitro and in vivo. Recently, several different methods have been reported, including the use of transcription factors and microRNAs. In addition, two in vivo studies showed heart function improvements with delivery of reprogramming factors in mouse infarcted hearts. Although many of these studies are at early preliminary stages, the plausibility of applying cardiac reprogramming on patients for regenerative purposes is exciting, and may lead to numerous novel research directions in the field. This review will discuss the history, recent advances and challenges of cellular reprogramming, specifically in the field of cardiac regeneration.

    View details for DOI 10.2174/1566523211313020007

    View details for Web of Science ID 000317846100007

    View details for PubMedID 23320478