ORCID Profile
0000-0001-6486-2003
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Publisher: Cold Spring Harbor Laboratory
Date: 17-01-2023
DOI: 10.1101/2023.01.17.524363
Abstract: Different signaling mechanisms concur to ensure robust tissue patterning and cell fate instruction during animal development. Most of these mechanisms rely on signaling proteins that are produced, transported and detected. The spatiotemporal dynamics of signaling molecules is largely unknown, yet it determines signal activity’s range and time frame. Here, we use the Caenorhabditis elegans embryo to study how Wnt ligands, an evolutionarily conserved family of signaling proteins, dynamically organize to establish cell polarity in a developing tissue. We identify how locally produced Wnt ligands spread to transmit information to distant target cells. With quantitative live imaging, we show that the Wnt ligands diffuse extracellularly through the embryo over a timescale shorter than the cell cycle. We extract diffusion coefficients of Wnt ligands and their receptor Frizzled (Fz) and characterize their co-localization. Integrating our different measurements and observations in a simple computational framework, we show how fast diffusion in the embryo can polarize target cells. Our results support diffusion-based long-range Wnt signaling, which is consistent with the dynamics of developing processes.
Publisher: eLife Sciences Publications, Ltd
Date: 09-07-2018
DOI: 10.7554/ELIFE.35800
Abstract: Intravital microscopy can provide unique insights into the function of biological processes in a native context. However, physiological motion caused by peristalsis, respiration and the heartbeat can present a significant challenge, particularly for functional readouts such as fluorescence lifetime imaging (FLIM), which require longer acquisition times to obtain a quantitative readout. Here, we present and benchmark Galene, a versatile multi-platform software tool for image-based correction of s le motion blurring in both time resolved and conventional laser scanning fluorescence microscopy data in two and three dimensions. We show that Galene is able to resolve intravital FLIM-FRET images of intra-abdominal organs in murine models and NADH autofluorescence of human dermal tissue imaging subject to a wide range of physiological motions. Thus, Galene can enable FLIM imaging in situations where a stable imaging platform is not always possible and rescue previously discarded quantitative imaging data.
Publisher: Elsevier BV
Date: 06-1993
Publisher: The Company of Biologists
Date: 2020
DOI: 10.1242/DEV.183186
Abstract: Wnt/β-catenin signaling has been implicated in the terminal asymmetric isions of neuronal progenitors in vertebrates and invertebrates. However, the role of Wnt ligands in this process remains poorly characterized. Here we used the terminal isions of the embryonic neuronal progenitors in C. elegans to characterize the role of Wnt ligands during this process focusing on a lineage that produces the cholinergic interneuron AIY. We observed that during interphase the neuronal progenitor is elongated along the anteroposterior axis, then ides along its major axis, generating an anterior and a posterior daughter with different fates. Using time-controlled perturbations, we show that three Wnt ligands, which are transcribed at higher levels at the posterior of the embryo, regulate the orientation of the neuronal progenitor and its asymmetric ision. We also identified a role for a Wnt receptor (MOM-5) and a cortical transducer APC (APR-1), which are respectively enriched at the posterior and anterior poles of the neuronal progenitor. Our study establishes a role for Wnt ligands in the regulation of the shape and terminal asymmetric isions of neuronal progenitors, and identifies downstream components.
Publisher: Springer Science and Business Media LLC
Date: 12-08-2019
DOI: 10.1038/S41467-019-10968-6
Abstract: Heterogeneous subtypes of cancer-associated fibroblasts (CAFs) coexist within pancreatic cancer tissues and can both promote and restrain disease progression. Here, we interrogate how cancer cells harboring distinct alterations in p53 manipulate CAFs. We reveal the existence of a p53-driven hierarchy, where cancer cells with a gain-of-function (GOF) mutant p53 educate a dominant population of CAFs that establish a pro-metastatic environment for GOF and null p53 cancer cells alike. We also demonstrate that CAFs educated by null p53 cancer cells may be reprogrammed by either GOF mutant p53 cells or their CAFs. We identify perlecan as a key component of this pro-metastatic environment. Using intravital imaging, we observe that these dominant CAFs delay cancer cell response to chemotherapy. Lastly, we reveal that depleting perlecan in the stroma combined with chemotherapy prolongs mouse survival, supporting it as a potential target for anti-stromal therapies in pancreatic cancer.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 05-04-2017
DOI: 10.1126/SCITRANSLMED.AAI8504
Abstract: Fine-tuned manipulation of tumor tension and vasculature enhances response to chemotherapy and impairs metastatic spread in pancreatic cancer.
Publisher: Springer Science and Business Media LLC
Date: 10-09-2020
DOI: 10.1038/S41586-020-2750-6
Abstract: The DNA sensor cyclic GMP-AMP synthase (cGAS) initiates innate immune responses following microbial infection, cellular stress and cancer
Publisher: Elsevier BV
Date: 06-2015
Publisher: American Association for the Advancement of Science (AAAS)
Date: 28-04-2023
Abstract: Aberrant AKT activation occurs in a number of cancers, metabolic syndrome, and immune disorders, making it an important target for the treatment of many diseases. To monitor spatial and temporal AKT activity in a live setting, we generated an Akt-FRET biosensor mouse that allows longitudinal assessment of AKT activity using intravital imaging in conjunction with image stabilization and optical window technology. We demonstrate the sensitivity of the Akt-FRET biosensor mouse using various cancer models and verify its suitability to monitor response to drug targeting in spheroid and organotypic models. We also show that the dynamics of AKT activation can be monitored in real time in erse tissues, including in in idual islets of the pancreas, in the brown and white adipose tissue, and in the skeletal muscle. Thus, the Akt-FRET biosensor mouse provides an important tool to study AKT dynamics in live tissue contexts and has broad preclinical applications.
Location: Switzerland
No related grants have been discovered for Pauline Melenec.