Sean Warren
A5033579370- Advanced Fluorescence Microscopy Techniques
- Cell Image Analysis Techniques
- Advanced Biosensing Techniques and Applications
- Optical Coherence Tomography Applications
- Cancer Cells and Metastasis
- Optical Imaging and Spectroscopy Techniques
- Photoacoustic and Ultrasonic Imaging
- Cellular Mechanics and Interactions
- 3D Printing in Biomedical Research
- Photodynamic Therapy Research Studies
- Receptor Mechanisms and Signaling
- Bone health and treatments
- Pancreatic and Hepatic Oncology Research
- Pancreatic function and diabetes
- Biotin and Related Studies
- Microtubule and mitosis dynamics
- Bone Metabolism and Diseases
- Hippo pathway signaling and YAP/TAZ
- Biomarkers in Disease Mechanisms
- Phagocytosis and Immune Regulation
- Random lasers and scattering media
- Advanced biosensing and bioanalysis techniques
- bioluminescence and chemiluminescence research
- Angiogenesis and VEGF in Cancer
- Retinal Development and Disorders
Garvan Institute of Medical Research
2015-2024
The Kinghorn Cancer Centre
2015-2024
UNSW Sydney
2015-2024
St Vincent's Clinic
2015-2023
University of Nebraska–Lincoln
2021
EMBL Australia
2021
Imperial College London
2009-2020
Georgia Institute of Technology
2019
Photonics (United States)
2017
Osteoclasts are large multinucleated bone-resorbing cells formed by the fusion of monocyte/macrophage-derived precursors that thought to undergo apoptosis once resorption is complete. Here, intravital imaging, we reveal RANKL-stimulated osteoclasts have an alternative cell fate in which they fission into daughter called osteomorphs. Inhibiting RANKL blocked this cellular recycling and resulted osteomorph accumulation. Single-cell RNA sequencing showed osteomorphs transcriptionally distinct...
Fine-tuned manipulation of tumor tension and vasculature enhances response to chemotherapy impairs metastatic spread in pancreatic cancer.
Fluorescence lifetime imaging (FLIM) is widely applied to obtain quantitative information from fluorescence signals, particularly using Förster Resonant Energy Transfer (FRET) measurements map, for example, protein-protein interactions. Extracting FRET efficiencies or population fractions typically entails fitting data complex decay models but such experiments are frequently photon constrained, live cell in vivo imaging, and this leads unacceptable errors when analysing on a pixel-wise...
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...
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,...
How cancer cells adapt to stress Bacteria harsh conditions such as antibiotic exposure by acquiring new mutations, a process called stress-induced mutagenesis. Cipponi et al. investigated whether similar programs of mutagenesis play role in the response targeted therapies. Using vitro models intense drug selection and genome-wide functional screens, authors found evidence for an analogous showed that it is regulated mammalian target rapamycin (mTOR) signaling pathway. This pathway appears...
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...
(Cell 184, 1330–1347.e1–e13; March 4, 2021) As a result of an author oversight in the originally published version this article, name author, Alexander Corr, did not appear list. This error has now been corrected article online, and contributions have updated accordingly to reflect Corr’s scRNA-seq analysis. Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorptionMcDonald et al.CellFebruary 25, 2021In BriefTracking osteoclasts cycles fission fusion reveals...
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,...
Application of advanced intravital imaging facilitates dynamic monitoring pathway activity upon therapeutic inhibition. Here, we assess resistance to inhibition the PI3K within hypoxic microenvironment pancreatic ductal adenocarcinoma (PDAC) and identify a phenomenon whereby pronounced hypoxia-induced is observed for three clinically relevant inhibitors. To address this clinical problem, have mapped tumor hypoxia by both immunofluorescence phosphorescence lifetime oxygen-sensitive...
Abstract A fluorescence lifetime imaging (FLIM) technology platform intended to read out changes in Förster resonance energy transfer (FRET) efficiency is presented for the study of protein interactions across drug‐discovery pipeline. FLIM provides a robust, inherently ratiometric modality drug discovery that could allow same sensor constructs be translated from automated cell‐based assays through small transparent organisms such as zebrafish mammals. To this end, an multiwell‐plate reader...
We present the first detailed study using multispectral multiphoton fluorescence lifetime imaging to differentiate basal cell carcinoma cells (BCCs) from normal keratinocytes. Images were acquired 19 freshly excised BCCs and 27 samples of skin (in & ex vivo). Features images used discriminate with a sensitivity/specificity 79%/93% respectively. A mosaic BCC covering >1 mm2 is also presented, demonstrating potential for tumour margin delineation. Using 10,462 manually segmented image data, we...
Multiplexed imaging of Förster Resonance Energy Transfer (FRET)-based biosensors potentially presents a powerful approach to monitoring the spatio-temporal correlation signalling pathways within single live cell. Here, we discuss potential homo-FRET based facilitate multiplexed imaging. We demonstrate that between pleckstrin homology domains Akt (Akt-PH) labelled with mCherry may be used monitor 3'-phosphoinositide accumulation in cells and show how global analysis time resolved fluorescence...
Intravital imaging guides a personalized medicine approach to target mechanoreciprocity in pancreatic cancer.
Intravital microscopy can provide unique insights into the function of biological processes in a native context. However, physiological motion caused by peristalsis, respiration and heartbeat present significant challenge, particularly for functional readouts such as fluorescence lifetime imaging (FLIM), which require longer acquisition times to obtain quantitative readout. Here, we benchmark Galene, versatile multi-platform software tool image-based correction sample blurring both time...
Fluorescence lifetime imaging (FLIM) combined with optical projection tomography (OPT) has the potential to map Förster resonant energy transfer (FRET) readouts in space and time intact transparent or near live organisms such as zebrafish larvae, thereby providing a means visualise cell signalling processes their physiological context. Here first application of FLIM OPT read out biological function transgenic larvae using genetically expressed FRET biosensor is reported. Apoptosis,...
This paper demonstrates multiphoton excited fluorescence imaging through a polarisation maintaining multicore fiber (PM-MCF) while the is dynamically deformed using all-proximal detection. Single-shot proximal measurement of relative optical path lengths all cores PM-MCF in double pass achieved Mach-Zehnder interferometer read out by scientific CMOS camera operating at 416 Hz. A non-linear least squares fitting procedure then employed to determine deformation-induced lateral shift excitation...
Pancreatic ductal adenocarcinoma (PDAC) is characterized by increasing fibrosis, which can enhance tumor progression and spread. Here, we undertook an unbiased temporal assessment of the matrisome highly metastatic KPC (
When performing multiphoton fluorescence lifetime imaging in multiple spectral emission channels, an instrument response function must be acquired each channel if accurate measurements of complex decays are to performed. Although this can achieved using the reference reconvolution technique, it is difficult identify suitable fluorophores with a mono-exponential decay across broad spectrum. We present solution problem by measuring IRF ultrafast luminescence from gold nanorods. show that...
We have compared the performance of two Troponin-C-based calcium FRET sensors using fluorescence lifetime read-outs. The first sensor, TN-L15, consists a Troponin-C fragment inserted between CFP and Citrine while second called mTFP-TnC-Cit, was realized by replacing in TN-L15 with monomeric Teal Fluorescent Protein (mTFP1). Using cytosol preparations transiently transfected mammalian cells, we measured decay profiles these at controlled concentrations time-correlated single photon counting....