A5067376769- Pancreatic and Hepatic Oncology Research
- Epigenetics and DNA Methylation
- Cancer Cells and Metastasis
- Genetics and Neurodevelopmental Disorders
- Pancreatic function and diabetes
- Single-cell and spatial transcriptomics
- Hedgehog Signaling Pathway Studies
- Cancer Genomics and Diagnostics
- Immune cells in cancer
- Advanced biosensing and bioanalysis techniques
- DNA and Nucleic Acid Chemistry
- Phagocytosis and Immune Regulation
- Cancer Immunotherapy and Biomarkers
- Genomics and Rare Diseases
- Ferroptosis and cancer prognosis
- Cancer, Hypoxia, and Metabolism
- RNA Interference and Gene Delivery
- Digestive system and related health
- Cancer Mechanisms and Therapy
- Click Chemistry and Applications
- Pancreatitis Pathology and Treatment
- Microbial Metabolism and Applications
- Caveolin-1 and cellular processes
- Cancer-related gene regulation
- Ubiquitin and proteasome pathways
University of Cambridge
2012-2025
Cancer Research UK
2012-2024
Cancer Research UK Cambridge Center
2014-2024
Lustgarten Foundation
2014-2021
Cold Spring Harbor Laboratory
2014-2020
Massachusetts Institute of Technology
2020
Cancer Center at Cold Spring Harbor Laboratory
2018
Euroitalia (Italy)
1954
Pancreatic stellate cells (PSCs) differentiate into cancer-associated fibroblasts (CAFs) that produce desmoplastic stroma, thereby modulating disease progression and therapeutic response in pancreatic ductal adenocarcinoma (PDA). However, it is unknown whether CAFs uniformly carry out these tasks or if subtypes of with distinct phenotypes PDA exist. We identified a CAF subpopulation elevated expression α-smooth muscle actin (αSMA) located immediately adjacent to neoplastic mouse human...
Cancer-associated fibroblasts (CAF) are major players in the progression and drug resistance of pancreatic ductal adenocarcinoma (PDAC). CAFs constitute a diverse cell population consisting several recently described subtypes, although extent CAF heterogeneity has remained undefined. Here we use single-cell RNA sequencing to thoroughly characterize neoplastic tumor microenvironment content human mouse PDAC tumors. We corroborate presence myofibroblastic inflammatory define their unique gene...
Abstract Pancreatic ductal adenocarcinoma (PDAC) is poorly responsive to therapies and histologically contains a paucity of neoplastic cells embedded within dense desmoplastic stroma. Within the stroma, cancer-associated fibroblasts (CAF) secrete tropic factors extracellular matrix components, have been implicated in PDAC progression chemotherapy resistance. We recently identified two distinct CAF subtypes characterized by either myofibroblastic or inflammatory phenotypes; however,...
Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease characterized by an extensive fibroinflammatory stroma, which includes abundant cancer-associated fibroblast (CAF) populations. PDAC CAFs are heterogeneous, but the nature of this heterogeneity incompletely understood. The Hedgehog pathway functions in paracrine manner, with ligands secreted cancer cells signaling to stromal microenvironment. Previous reports investigating role have been contradictory, alternately...
Four-stranded G-quadruplex DNA secondary structures have recently been visualized in the nuclei of human cultured cells. Here, we show that BG4, a G-quadruplex-specific antibody, can be used to stain patient-derived tissues using immunohistochemistry. We observe significantly elevated number G-quadruplex-positive cancers liver and stomach as compared background non-neoplastic tissue. Our results suggest formation detected measured material may characteristic some cancers.
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. Cancer-associated fibroblasts (CAFs) are recognized potential therapeutic targets, but poor understanding of these heterogeneous cell populations limited the development effective treatment strategies. We previously identified transforming growth factor beta (TGF-β) as main driver myofibroblastic CAFs (myCAFs). Here, we show that epidermal receptor/Erb-B2 receptor (EGFR/ERBB2) signaling is induced by TGF-β in myCAFs through an...
It all clicks into place: A potent telomere-targeting small molecule has been identified by using the copper-free 1,3-dipolar cycloaddition of a series alkyne and azide building blocks catalyzed non-Watson-Crick DNA secondary structure (see picture). This method rapidly identifies, otherwise unanticipated, small-molecule probes to selectively target given RNA or DNA.
Telomeric repeat-containing RNA (TERRA) is important for telomere regulation, but the structural basis how TERRA localizes to chromosome ends unknown. Here we report on studies exploring whether G-quadruplex structure critical binding telomeres. We demonstrate that telomeric protein TRF2 binds via interactions necessitate formation of a rather than sequence per se. also show simultaneously and duplex or DNA. These observations suggest key feature organization.
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, and new therapies are needed. Altered metabolism is cancer vulnerability, several metabolic pathways have been shown to promote PDAC. However, the changes in cholesterol their role during PDAC progression remain largely unknown. Here we used organoid mouse models determine drivers of altered consequences its disruption on tumor progression. We identified sterol O-acyltransferase 1 (SOAT1) as key player sustaining mevalonate...
Tumors are composed of many different cell types including cancer cells, fibroblasts, and immune cells. Dissecting functional metabolic differences between within a mixed population can be challenging due to the rapid turnover metabolites relative time needed isolate To overcome this challenge, we traced isotope-labeled nutrients into macromolecules that turn over more slowly than metabolites. This approach was used assess fibroblast metabolism in murine pancreatic organoid-fibroblast...
A highly aggressive subset of pancreatic ductal adenocarcinomas undergo trans-differentiation into the squamous lineage during disease progression. Here, we investigated whether human and mouse cancer cells can influence phenotype non-neoplastic in tumor microenvironment. Conditioned media experiments revealed that secrete factors recruit neutrophils convert stellate cancer-associated fibroblasts (CAFs) express inflammatory cytokines at high levels. We use gain- loss-of-function approaches...
The pleural lining of the thorax regulates local immunity, inflammation and repair. A variety conditions, both benign malignant, including mesothelioma, can affect this tissue. lack knowledge concerning mesothelial stromal cells comprising pleura has hampered development targeted therapies. Here, we present first comprehensive single-cell transcriptomic atlas human parietal demonstrate its utility in elucidating biology. We confirm presence known universal fibroblasts describe novel,...
Abstract Our knowledge of the origins, heterogeneity, and functions cancer-associated fibroblasts (CAF) in pancreatic ductal adenocarcinoma (PDAC) has exponentially increased over last two decades. This been facilitated by implementation new models single-cell technologies. However, a few key studies preceded current exciting times CAF research were fundamental initiating investigation CAFs their roles PDAC. With study published Cancer Research 2008, Hwang colleagues have first to...
Alles klickt zusammen: Mittels kupferfreier 1,3-dipolarer Cycloaddition einer Serie von Alkin- und Azid-Bausteinen mit nicht-Watson-Crick-artigen DNA-Sekundärstruktur als Katalysator gelang die Identifizierung potenten Telomer-erkennenden niedermolekularen Verbindung (siehe Bild). Die Methode ist allgemein anwendbar liefert niedermolekulare Sonden, selektiv zwischen gegebenen RNA oder DNA unterscheiden können. Click chemistry has been broadly defined as chemical reactions capable of...
Abstract Pancreatic ductal adenocarcinoma (PDAC) contains an extensive stroma that modulates response to therapy, contributing the dismal prognosis associated with this cancer. Evidence suggests PDAC stromal composition is shaped by mutations within malignant cells, but most previous work has focused on pre-clinical models driven KrasG12D and mutant Trp53. Elucidation of contribution additional known oncogenic drivers, including KrasG12V mutation Smad4 loss, needed increase understanding...
<div>Abstract<p>Pancreatic ductal adenocarcinoma (PDAC) contains an extensive stroma that modulates response to therapy, contributing the dismal prognosis associated with this cancer. Evidence suggests PDAC stromal composition is shaped by mutations within malignant cells, but most previous work has focused on preclinical models driven <i>Kras</i><sup><i>G12D</i></sup> and mutant <i>Trp53</i>. Elucidation of contribution additional...
<p>Table S11</p>
<p>Table S12</p>