Hypoxia is an efficient inducer of inflammation, resulting in immune cell invasion into the oxygen-deprived tissue. Accumulation of metabolically highly active immune cells increases oxygen consumption, aggravating hypoxia and tissue damage. The aim of this project is to generate new hypoxia reporters (1) and reporter mouse lines (2) based on the oxygen-independent fluorescent protein UnaG, as well as metabolic reporters (3), which will be functionally tested and applied in preclinical models of myocardial infarction (4), kidney ischemia and intestinal infection.
Using probabilistic machine learning on the imaging data generated, we will attempt to analyse quantitatively tissue hypoxia across multiple imaging scales (5) with a particular focus on the explainability of our deep learning models (6) to ensure trustworthy predictions. These insights will feed back into the sensor design and reporter mouse generation to further optimise our multi-scale analysis of hypoxia, metabolism and cell migration.
The names of the principal investigators in our network have been bolded. Publications released prior to 2021, when funding for our network commenced, represent previous project-related work.
Accepted for publication
Kockwelp J, Thiele S, Kockwelp P, Bartsch, J, Schliemann C, Angenendt L, Risse B. Cell Selection-based Data Reduction Pipeline for Whole Slide Image Analysis of Acute Myeloid Leukemia. IEEE Xplore: accepted for publication.
2022
Eliat F, Sohn R, Renner H, Kagermeier T, Volkery S, Brinkmann H, Kirschnick N, Kiefer F, Grabos M, Becker K, Bedzhov I, Scholer HR, Bruder JM. Tissue clearing may alter emission and absorption properties of common fluorophores. Sci Rep 2022;12: 5551. Abstract
Peil J, Bock F, Kiefer F, Schmidt R, Heindl LM, Cursiefen C, Schlereth SL. New Therapeutic Approaches for Conjunctival Melanoma-What We Know So Far and Where Therapy Is Potentially Heading: Focus on Lymphatic Vessels and Dendritic Cells. Int J Mol Sci 2022;23Abstract
Reimche I, Yu H, Ariantari NP, Liu Z, Merkens K, Rotfuss S, Peter K, Jungwirth U, Bauer N, Kiefer F, Neudorfl J-M, Schmalz H-G, Proksch P, Teusch N. Phenanthroindolizidine Alkaloids Isolated from Tylophora ovata as Potent Inhibitors of Inflammation, Spheroid Growth, and Invasion of Triple-Negative Breast Cancer. Int J Mol Sci 2022;23Abstract
2021
Arasa J, Collado-Diaz V, Kritikos I, Medina-Sanchez JD, Friess MC, Sigmund EC, Schineis P, Hunter MC, Tacconi C, Paterson N, Nagasawa T, Kiefer F, Makinen T, Detmar M, Moser M, Lammermann T, Halin C. Upregulation of VCAM-1 in lymphatic collectors supports dendritic cell entry and rapid migration to lymph nodes in inflammation. J Exp Med 2021;218Abstract
Bian A, Jiang X, Berh D, Risse B. Resolving Colliding Larvae by Fitting ASM to Random Walker-Based Pre-Segmentations. IEEE/ACM Trans Comput Biol Bioinform 2021;18: 1184-1194. Abstract
Drees D, Scherzinger A, Hagerling R, Kiefer F, Jiang X. Scalable robust graph and feature extraction for arbitrary vessel networks in large volumetric datasets. BMC Bioinformatics 2021;22: 346. Abstract
Kirschnick N, Drees D, Redder E, Erapaneedi R, Pereira da Graca A, Schafers M, Jiang X, Kiefer F. Rapid methods for the evaluation of fluorescent reporters in tissue clearing and the segmentation of large vascular structures. iScience 2021;24: 102650. Abstract
Kong C, Bobe S, Pilger C, Lachetta M, Oie CI, Kirschnick N, Monkemoller V, Hubner W, Forster C, Schuttpelz M, Kiefer F, Huser T, Schulte Am Esch J. Multiscale and Multimodal Optical Imaging of the Ultrastructure of Human Liver Biopsies. Front Physiol 2021;12: 637136. Abstract
Redder E, Kirschnick N, Bobe S, Hagerling R, Hansmeier NR, Kiefer F. Vegfr3-tdTomato, a reporter mouse for microscopic visualization of lymphatic vessel by multiple modalities. PLoS One 2021;16: e0249256. Abstract
Sadras T, Martin M, Kume K, Robinson ME, Saravanakumar S, Lenz G, Chen Z, Song JY, Siddiqi T, Oksa L, Knapp AM, Cutler J, Cosgun KN, Klemm L, Ecker V, Winchester J, Ghergus D, Soulas-Sprauel P, Kiefer F, Heisterkamp N, Pandey A, Ngo V, Wang L, Jumaa H, Buchner M, Ruland J, Chan W-C, Meffre E, Martin T, Muschen M. Developmental partitioning of SYK and ZAP70 prevents autoimmunity and cancer. Mol Cell 2021;81: 2094-2111.e9. Abstract
2018
Hägerling R, Hoppe E, Dierkes C, Stehling M, Makinen T, Butz S, Vestweber D, Kiefer F. Distinct roles of VE‐cadherin for development and maintenance of specific lymph vessel beds. EMBO J 2018: e98271. Abstract
Klemm S, Jiang X, Risse B. Deep distance transform to segment visually indistinguishable merged objects. In: Proc. of 40th German Conference on Pattern Recognition (GCPR), Stuttgart 2018: 422-433.
Orlich M, Kiefer F. A qualitative comparison of ten tissue clearing techniques. Histol Histopathol 2018;33: 181-199. Abstract
2017
Hagerling R, Drees D, Scherzinger A, Dierkes C, Martin-Almedina S, Butz S, Gordon K, Schafers M, Hinrichs K, Ostergaard P, Vestweber D, Goerge T, Mansour S, Jiang X, Mortimer PS, Kiefer F. VIPAR, a quantitative approach to 3D histopathology applied to lymphatic malformations. JCI Insight 2017;2: e93424. Abstract
2016
Erapaneedi R, Belousov VV, Schafers M, Kiefer F. A novel family of fluorescent hypoxia sensors reveal strong heterogeneity in tumor hypoxia at the cellular level. Embo J 2016;35: 102-113. Abstract
2014
Lammel U, Bechtold M, Risse B, Berh D, Fleige A, Bunse I, Jiang X, Klambt C, Bogdan S. The Drosophila FHOD1-like formin Knittrig acts through Rok to promote stress fiber formation and directed macrophage migration during the cellular immune response. Development 2014;141: 1366-1380. Abstract
2013
Hägerling R, Pollmann C, Andreas M, Schmidt C, Nurmi H, Adams RH, Alitalo K, Andresen V, Schulte-Merker S, Kiefer F. A novel multistep mechanism for initial lymphangiogenesis in mouse embryos based on ultramicroscopy. EMBO J 2013;32: 629-644. Abstract
Risse B, Thomas S, Otto N, Lopmeier T, Valkov D, Jiang X, Klambt C. FIM, a novel FTIR-based imaging method for high throughput locomotion analysis. PLoS One 2013;8: e53963. Abstract
Sander M, Squarr AJ, Risse B, Jiang X, Bogdan S. Drosophila pupal macrophages--a versatile tool for combined ex vivo and in vivo imaging of actin dynamics at high resolution. Eur J Cell Biol 2013;92: 349-354. Abstract
