Biology subjects

Kemp, V.

Publications and source records attributed to Kemp, V..

3 recordsLinked to original sources

bioRxiv2026

Bulk RNA sequencing deconvolution of pancreatic ductal adenocarcinoma identifies cancer-associated fibroblast subsets associated with survival and tumor microenvironment composition

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer characterized by a high abundance of cancer-associated fibroblasts (CAFs), which influence therapy response, tumor biology and tumor aggressiveness. CAFs are a heterogeneous cell type and previous single-cell RNA sequencing (scRNAseq) of PDAC tumors identified three main CAF subtypes: myofibroblastic, inflammatory and antigen-presenting CAFs (myCAF, iCAF, apCAF, respectively). However, scRNAseq on large patient cohorts is often not feasible due to costs and technical constraints. Therefore, bulk RNAseq deconvolution can be used to identify cell types within the heterogeneous tumor microenvironment. Here, Statescope deconvolution was used to identify different cell types of the tumor microenvironment within an early onset PDAC cohort, comprising 74 patients aged under 60. Three CAF populations were identified (iCAFs, myCAFs and desmoplastic CAFs), and their correlations with tumor microenvironment components, mutational signatures and survival were examined. iCAFs were associated with classical-like tumor cells, whereas myCAFs and desmoplastic CAFs correlated with basal-like tumor cells. Desmoplastic CAFs are associated with inflammatory granulocytes/neutrophils, while negatively associating with monocyte-derived macrophages and immature/transitional B cells. No associations were observed between mutational signatures and the abundance of CAF and epithelial tumor subtypes. Interestingly, a high abundance of CAFs, and specifically increased iCAF abundance, was associated with improved survival. This iCAF-mediated survival effect was predominantly apparent in female patients. All in all, deconvolution of bulk RNA sequencing data, followed by its integration with clinical and biological parameters, reveals the heterogeneity and prognostic implications of CAF subpopulations in the tumor microenvironment of early onset PDAC patients.

cancer biology↗

bioRxiv2025

ZEB1, a novel regulator of Junctional Adhesion Molecule A, impacts sensitivity of pancreatic cancer-associated fibroblasts to oncolytic reovirus

Oncolytic virus (OV) therapy is a promising treatment for various tumors. However, in pancreatic ductal adenocarcinoma (PDAC), the high abundance of cancer-associated fibroblasts (CAFs) can limit OV therapy efficacy by impairing viral spread and anti-tumor immunity. We have previously shown that oncolytic reovirus infection of CAFs depends on expression of the reovirus entry receptor Junctional Adhesion Molecule A (JAM-A), which is not or lowly expressed in most PDAC CAFs. We propose that increasing JAM-A expression on CAFs will boost viral spread in a tumor. However, there are currently no known regulators of JAM-A expression. Therefore, we performed a genome-wide CRISPR/Cas9 knock-out screen to identify regulators of JAM-A expression. Ablation of the top negative regulator, Zinc Finger E-Box binding Homeobox 1 (ZEB1), in pancreatic fibroblasts led to strong JAM-A upregulation. We show that ZEB1 directly regulates JAM-A expression by binding to the E-box regions located within the JAM-A promotor. Importantly, ZEB1 ablation increased the sensitivity of fibroblasts to reovirus infection and subsequent cell death. Our work provides a novel overview of genes regulating JAM-A expression and provides a rational approach of combining ZEB1 inhibition with reovirus therapy to target both CAFs and tumor cells in stroma-rich tumors such as PDAC.

cancer biology↗

bioRxiv2022

Logging alters tropical forest structure, while conversion reduces biodiversity and functioning

The impacts of degradation and deforestation on tropical forests are poorly understood, particularly at landscape scales. We present an extensive ecosystem analysis of the impacts of logging and conversion of tropical forest to oil palm from a large-scale study in Borneo, synthesizing responses from 82 variables categorized into four ecological levels spanning a broad suite of ecosystem properties: 1) structure and environment, 2) species traits, 3) biodiversity, and 4) ecosystem functions. Responses were highly heterogeneous and often complex and non-linear. Variables that were directly impacted by the physical process of timber extraction, such as soil structure, were sensitive to even moderate amounts of logging, whereas measures of biodiversity and ecosystem functioning were generally resilient to logging but more affected by conversion to oil palm plantation. One-Sentence SummaryLogging tropical forest mostly impacts structure while biodiversity and functions are more vulnerable to habitat conversion.

ecology↗