Morghan C. Lucas
A5074452786- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Cancer-related molecular mechanisms research
- Cancer Cells and Metastasis
- RNA Research and Splicing
- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- Cancer Research and Treatments
- Genomics and Phylogenetic Studies
- Molecular Biology Techniques and Applications
- Cancer-related gene regulation
- Microtubule and mitosis dynamics
- Mitochondrial Function and Pathology
- Phagocytosis and Immune Regulation
- Neurogenetic and Muscular Disorders Research
- Microbial metabolism and enzyme function
- Pancreatic function and diabetes
- Genetic Neurodegenerative Diseases
- Cell death mechanisms and regulation
- Cytomegalovirus and herpesvirus research
- Neuroscience of respiration and sleep
- Single-cell and spatial transcriptomics
- Cell Adhesion Molecules Research
- Treatment of Major Depression
- Plant Micronutrient Interactions and Effects
LMU Klinikum
2024-2025
Ludwig-Maximilians-Universität München
2024-2025
Medical Genetics Center
2024-2025
Universitat Pompeu Fabra
2019-2024
Garvan Institute of Medical Research
2015-2024
UNSW Sydney
2015-2024
Centre for Genomic Regulation
2019-2024
The Kinghorn Cancer Centre
2015-2024
Friedrich Baur Stiftung
2024
St Vincent's Clinic
2015-2021
Abstract The epitranscriptomics field has undergone an enormous expansion in the last few years; however, a major limitation is lack of generic methods to map RNA modifications transcriptome-wide. Here, we show that using direct sequencing, N 6 -methyladenosine (m A) can be detected with high accuracy, form systematic errors and decreased base-calling qualities. Specifically, find our algorithm, trained m A-modified unmodified synthetic sequences, predict A ~90% accuracy. We then extend...
Fine-tuned manipulation of tumor tension and vasculature enhances response to chemotherapy impairs metastatic spread in pancreatic cancer.
Abstract Heterogeneous subtypes of cancer-associated fibroblasts (CAFs) coexist within pancreatic cancer tissues and can both promote restrain disease progression. Here, we interrogate how cells harboring distinct alterations in p53 manipulate CAFs. We reveal the existence a p53-driven hierarchy, where with gain-of-function (GOF) mutant educate dominant population CAFs that establish pro-metastatic environment for GOF null alike. also demonstrate educated by may be reprogrammed either or...
The tumour stroma, and in particular the extracellular matrix (ECM), is a salient feature of solid tumours that plays crucial role shaping their progression. Many desmoplastic including breast cancer involve significant accumulation type I collagen. However, recently it has become clear precise distribution organisation molecules such as collagen equally important abundance. Cancer-associated fibroblasts (CAFs) coexist within tissues play both pro- anti-tumourigenic roles through remodelling...
Abstract The concept that extracellular vesicles (EVs) from the diet can be absorbed by intestinal tract of consuming organism, bioavailable in various organs, and in-turn exert phenotypic changes is highly debatable. Here, we isolate EVs both raw commercial bovine milk characterize them electron microscopy, nanoparticle tracking analysis, western blotting, quantitative proteomics small RNA sequencing analysis. Orally administered milk-derived survive harsh degrading conditions gut, mice,...
Transfer RNAs (tRNAs) play a central role in protein translation. Studying them has been difficult part because simple method to simultaneously quantify their abundance and chemical modifications is lacking. Here we introduce Nano-tRNAseq, nanopore-based approach sequence native tRNA populations that provides quantitative estimates of both abundances modification dynamics single experiment. We show default nanopore sequencing settings discard the vast majority reads, leading poor yields...
Abstract The lysyl oxidase family represents a promising target in stromal targeting of solid tumors due to the importance this crosslinking and stabilizing fibrillar collagens its known role tumor desmoplasia. Using small-molecule drug-design approaches, we generated validated PXS-5505, first-in-class highly selective potent pan-lysyl inhibitor. We demonstrate vitro vivo that inhibition decreases chemotherapy-induced pancreatic desmoplasia stiffness, reduces cancer cell invasion metastasis,...
Lysyl Oxidase-like 2 (LOXL2), a member of the lysyl oxidase family amine oxidases is known to be important in normal tissue development and homeostasis, as well onset progression solid tumors. Here we tested anti-tumor properties two generations novel small molecule LOXL2 inhibitor MDA-MB-231 human model breast cancer. We confirmed functional role for activity primary Inhibition inhibited growth tumors reduced tumor angiogenesis. Dual inhibition LOX showed greater effect also led lower...
Highlights•Live quantification of RhoA activity during development and disease progression•Real-time visualization signaling in normal skin, osteocytes, neutrophils•Monitoring deregulation invasive mammary pancreatic cancers•Longitudinal vivo imaging inhibition using optical windowsSummaryThe small GTPase is involved a variety fundamental processes tissue. Spatiotemporal control thought to govern mechanosensing, growth, motility cells, while its associated with development. Here, we describe...
Pancreatic cancer has a devastating prognosis, with an overall 5-year survival rate of ~8%, restricted treatment options and characteristic molecular heterogeneity. SerpinB2 expression, particularly in the stromal compartment, is associated reduced metastasis prolonged pancreatic ductal adenocarcinoma (PDAC) our genomic analysis revealed that SERPINB2 frequently deleted PDAC. We show required by cells for normal collagen remodelling vitro, regulating fibroblast interaction engagement...
RNA modifications play central roles in cellular fate and differentiation. However, the machinery responsible for placing, removing, recognizing more than 170 remains largely uncharacterized poorly annotated, we currently lack integrative studies that identify which modification-related proteins (RMPs) may be dysregulated each cancer type.
Nanopore sequencing enables direct measurement of RNA molecules without conversion to cDNA, thus opening the gates a new era for biology. However, lack molecular barcoding nanopore data sets severely affects applicability this technology biological samples, where availability is often limited. Here, we provide first experimental protocol and associated algorithm barcode demultiplex sets. Specifically, present novel robust approach accurately classify raw signal by transforming current...
The existence of naturally occurring ribosome heterogeneity is now a well-acknowledged phenomenon. However, whether this leads to functionally diverse 'specialized ribosomes' still controversial topic. Here, we explore the biological function RPL3L (uL3L), ribosomal protein (RP) paralogue RPL3 (uL3) that exclusively expressed in skeletal muscle and heart tissues, by generating viable homozygous Rpl3l knockout mouse strain. We identify rescue mechanism which, upon depletion, becomes...
In recent years, nanopore direct RNA sequencing (DRS) became a valuable tool for studying the epitranscriptome, owing to its ability detect multiple modifications within same full-length native molecules. Although can be identified in form of systematic basecalling "errors" DRS data sets,
E-cadherin-mediated cell-cell junctions play a prominent role in maintaining the epithelial architecture. The disruption or deregulation of these adhesions cancer can lead to collapse tumor epithelia that precedes invasion and subsequent metastasis. Here we generated an E-cadherin-GFP mouse enables intravital photobleaching quantification E-cadherin mobility live tissue without affecting normal biology. We demonstrate broad applications this by examining regulation multiple tissues,...
<ns4:p>Tumour metastasis is a dynamic and systemic process. It no longer seen as tumour cell-autonomous program but multifaceted complex series of events, which influenced by the intrinsic cellular mutational burden cancer cells numerous bidirectional interactions between malignant non-malignant fine-tuned various extrinsic cues extracellular matrix. In biology, process one most technically challenging aspects biology to study. As result, new platforms technologies are continually being...
Metastatic disease is largely resistant to therapy and accounts for almost all cancer deaths. Myeloid cell leukemia-1 (MCL-1) an important regulator of survival chemo-resistance in a wide range malignancies, thus its inhibition may prove be therapeutically useful. To examine whether targeting MCL-1 provide effective treatment breast cancer, we constructed inducible models BIMs2A expression (a specific inhibitor) MDA-MB-468 (MDA-MB-468-2A) MDA-MB-231 (MDA-MB-231-2A) cells. caused apoptosis...
<ns4:p>Tumour metastasis is a dynamic and systemic process. It no longer seen as tumour cell-autonomous program but multifaceted complex series of events, which influenced by the intrinsic cellular mutational burden cancer cells numerous bidirectional interactions between malignant non-malignant fine-tuned various extrinsic cues extracellular matrix. In biology, process one most technically challenging aspects biology to study. As result, new platforms technologies are continually being...
Intravital imaging guides a personalized medicine approach to target mechanoreciprocity in pancreatic cancer.
Mammalian ribosomal RNA (rRNA) molecules are highly abundant RNAs, decorated with over 220 rRNA modifications. Previous works have shown that some modification types can be dynamically regulated; however, how and when the mammalian landscape is remodeled remains largely unexplored. Here, we employ direct nanopore sequencing to chart human mouse epitranscriptome across tissues, developmental stages, cell disease. Our analyses reveal multiple sites differentially modified in a tissue- and/or...
Hintergrund: Die Myotone Dystrophie Typ 2 (DM2) ist eine Multisystemerkrankung für deren Diagnose molekulargenetische Untersuchung zum Nachweis einer ursächlichen (CCTG)n-Repeatexpansion im CNBP Gen essenziell ist. Struktur der Repeatexpansionen aufgrund ihres ausgeprägten somatischen Mosaiks und hohen Länge bisher nur eingeschränkt charakterisiert worden. Diagnostik bedarf besonderer Methoden.
Hintergrund: Trotz ihrer hohen Prävalenz in der europäischen Population ist die Testung auf FSHD derzeit nur mit eingeschränkter Genauigkeit möglich. Die Methylierung wurde kürzlich als präziseste Marker validiert und ihre Verwendung konnte Diagnostik wesentlich verbessern, jedoch Messung aufwändig teilweise technisch limitiert.