A5086482018- Zebrafish Biomedical Research Applications
- Cell Image Analysis Techniques
- Hippo pathway signaling and YAP/TAZ
- Mathematical Biology Tumor Growth
- CRISPR and Genetic Engineering
- Bacterial biofilms and quorum sensing
- Bacteriophages and microbial interactions
- Molecular Biology Techniques and Applications
- Congenital heart defects research
- Single-cell and spatial transcriptomics
- Image Retrieval and Classification Techniques
- 3D Printing in Biomedical Research
- Receptor Mechanisms and Signaling
- Microbial Community Ecology and Physiology
- Pancreatic function and diabetes
- AI in cancer detection
- Mathematical and Theoretical Epidemiology and Ecology Models
- Evolution and Genetic Dynamics
- Cellular Mechanics and Interactions
- Vibrio bacteria research studies
- Melanoma and MAPK Pathways
- Cancer Genomics and Diagnostics
- Diabetes and associated disorders
- Topological and Geometric Data Analysis
- Evolutionary Game Theory and Cooperation
University of Copenhagen
2010-2023
Roskilde University
2022
Technical University of Denmark
2022
Memorial Sloan Kettering Cancer Center
2013-2021
Novo Nordisk Foundation
2019-2021
Kettering University
2015-2020
Berlin Institute of Health at Charité - Universitätsmedizin Berlin
2018
Charité - Universitätsmedizin Berlin
2018
Abstract Cellular plasticity is a state in which cancer cells exist along reversible phenotypic spectrum, and underlies key traits such as drug resistance metastasis. Melanoma linked to phenotype switching, where the microenvironment induces switches between invasive/MITF LO versus proliferative/MITF HI states. Since MITF also pigmentation, we hypothesize that macrometastatic success should be favoured by microenvironments induce /differentiated/proliferative state. Zebrafish imaging...
Metastasis is the defining feature of advanced malignancy, yet remains challenging to study in laboratory environments. Here, we describe a high-throughput zebrafish system for comprehensive, vivo assessment metastatic biology. First, generated several stable cell lines from melanomas transgenic mitfa-BRAF(V600E);p53(-/-) fish. We then transplanted melanoma cells into transparent casper strain enable highly quantitative measurement process at single-cell resolution. Using computational image...
Bacteriophage are voracious predators of bacteria and a major determinant in shaping bacterial life strategies. Many phage species virulent, meaning that infection leads to certain death the host immediate release large batch progeny. Despite this apparent voraciousness, have stably coexisted with virulent phages for eons. Here, using individual-based stochastic spatial models, we study conditions achieving coexistence on edge between two habitats, one which is refuge hostile whereas other...
Many bacteria secrete compounds, which act as public goods. Such compounds are often under quorum sensing (QS) regulation, yet it is not understood exactly when may gain from having a good QS regulation. Here, we show that the optimal production rate per cell function of population size (the curve, OPC) depend crucially on cost and benefit functions OPC will fall into one two categories: Either continuous or jumps zero discontinuously at critical size. If, e.g., has accelerating returns...
Virulent phages and their bacterial hosts represent an unusual sort of predator-prey system where each time a prey is eaten, hundreds new predators are born. It puzzling how, despite the apparent effectiveness phage predators, they manage to avoid driving extinction. Here we consider phage-bacterial ecosystem on two-dimensional (2-d) surface show that homogeneous space in itself enhances coexistence. We analyze different behavioral mechanisms can facilitate coexistence spatial environment....
SUMMARY In melanoma, transcriptional profiling has revealed multiple co-existing cell states, including proliferative versus invasive sub-populations that have been posited to represent a “go or grow” tradeoff. Both of these populations are maintained in tumors, but how they physically interact promote metastasis is unknown. We demonstrate subpopulations form spatially structured heterotypic clusters cooperate the seeding metastasis. unexpectedly found INV cells were tightly adherent each...
Abstract Metastasis is the primary cause of cancer death, yet we know little about what determines its timing and aggressiveness. In melanoma, transcriptional profiling has revealed multiple co-existing cell states, including proliferative (PRO) versus invasive (INV) subpopulations that have been posited to represent a “go or grow” tradeoff in etiology metastasis. Although both these populations are present tumors metastases, known how they physically interact with each other tumor...
Abstract The genetic and environmental heterogeneity associated with tumors makes cancer treatment recovery a difficult unpredictable process. Patients initially similar disease can experience vastly different outcomes including sustained recovery, refractory or, remarkably, recurrence years after treatment. Mathematical models informed animal human data provide tools for theoretical clinical understanding of progression the causes highly variant outcomes. This work postulates population...
Motivated by the challenging segmentation task of pancreatic tubular networks, this paper tackles two commonly encountered problems in biomedical imaging: Topological consistency segmentation, and expensive or difficult annotation. Our contributions are following: a) We propose a topological score which measures both geometric between predicted ground truth segmentations, applied to model selection validation. b) provide full deep-learning methodology for noisy on time-series image data. In...
We have developed a protocol to quantify the position of cell in branched structure based on two-dimensional microscopy images tissue sections. Biological structures include organs such as lungs, kidneys, and pancreas. In these organs, fate has been correlated with position, qualitative estimate. However, quantitative means evaluating lacking. With this protocol, correlation between was measured mouse embryonic For complete details use execution please refer Nyeng et al. (2019).
<p>Supplemental Table 3. This provides all of the features initially extracted from zebrafish images and an explanation how each was used or not.</p>
<p>These are the legends for Supplemental Figures 1-20</p>
<p>Supplemental Video 1: 12 hours post-transplantation of ZMEL1-GFP cells into larval zebrafish showing in widespread circulation</p>
<p>Supplemental Figures 1-20. Supplemental Figure 1: Metastatic behavior of primary melanoma transplants. 2: Demonstration cDNA overexpression in the ZMEL1 line. 3: CRISPR/Cas9-mediated mutation 4: SURVEYOR assay to assess rates cells nucleofected with CRISPR/Cas9 constructs. 5: Gene Set Enrichment Analysis (GSEA) for transcriptional signature compared NCI60 human cancer cell lines (dataset NCI60GSE5846). 6: Heatmap plot 7: transgenic mitf-BRAF;p53 tumors. 8: 9: Ingenuity Pathway...
<p>Supplemental Video 2: Time-lapse video from 1-21 days post transplantation of ZMEL1-GFP cells into adult zebrafish showing primary growth and metastatic spread.</p>
<p>This file provides additional information on reagents and software analysis of images.</p>
<p>Supplemental Table 2. This data provides transcriptomic analysis of the ZMEL1 line (RNA-seq) along with GSEA comparing to either human melanomas or primary zebrafish transgenic melanomas.</p>
<p>Supplemental Table 1. This is data on the number of attempted zebrafish cell lines and our success rates in terms long term propagation weaning off fibronectin.</p>
Abstract During embryogenesis dynamic changes in tissue architecture transform primitive anlages to functional organs. Here we document real time how pancreatic lumens are derived and transformed using a new apical-polarity mouse reporter. Our 4D imaging data reveals remodeling of apical proteins primarily drive each stage duct development. Furthermore, pinpoint two unique transitions during lumenogenesis. Contrary current “ de novo ” models polarity acquisition, show that expansion...