Picture of two people in a microscopy laboratory
© EIMI

Intravital Molecular Imaging Lab (Prof. Friedemann Kiefer)

We are interested in the morphogenetic processes that shape and maintain the vascular systems, especially lymphatic vessels, during development but also in healthy and diseased adult life. In particular, we are interested by the interplay of blood and lymphatic vessels, tissue oxygenation (or the lack thereof i.e. hypoxia) and leukocytes and its relevance for organ function in various developmental and pathological settings. Our work rests on the intense use and refinement of cutting edge microscopy in combination with reporter models to visualize the individual actors of this ménage à trois within the context of the intact tissue or even dynamically in the living organism.

  • Research News & Views

     

  • Projects

    Imaging of inflammation using microscopy (left) and whole-body imaging (PET-CT, right)
    © Uni MS – AG Kiefer/AG Schäfers

    Collaborative Research Centre “inSight – Multiscale imaging of organ-specific inflammation” (CRC 1450)

    In this collaborative research project, we focus on the question of how the body regulates inflammation in different organs and, to this end, develop a specific imaging methodology that brings together information from single cells to entire organisms.

    Spokesperson: Michael Schäfers (EIMI), Deputy Spokesperson: Friedemann Kiefer (EIMI)
    Project term: 01/2021 - 12/2024
    Project number: CRC/1450 | DFG

     

    Atherom
    © EIMI

    Assessing macrophage activation, migration and fate during a novel anti-atherosclerotic intervention

    Atherosclerosis is a chronic inflammatory disease of the vessel wall characterized by lipid accumulation and macrophage infiltration, which is attributed to hypercholesterolemia, smoking and obesity. Ultimately, atherosclerosis may cause thrombotic events making it the leading cause of ischemic heart disease, stroke and peripheral vascular disease. In this research project, novel reagents to influence the polarization of macrophages are tested as a potential tools to change macrophage migration and thereby attenuate atherosclerotic plaque formation in mouse models.

    Principal investigators: Friedemann Kiefer (EIMI)
    Project term: 01/2020 - 12/2022
    Project number: Kief1/019/20 | Medical Faculty, University of Münster

    Distribution of immune cells in the body of a mouse, imaged with optical imaging
    © S. Gran & L. Honold et al./Theranostics 2018(8)

    Immune-Image

    In this project, we develop methods for monitoring immune cells before, during and after immune treatment. Initially, we will look at these processes in animal models for different diseases – with the aim of translating the results and methods to patients mid-term enabling us to establish image-guided immunotherapies with improved efficacy in diseases such as cancer or inflammation.

    Coordinator: Albert D. Windhorst (Amsterdam University Medical Centre, the Netherlands)
    EIMI members involved as partners: Michael Schäfers, Andreas Jacobs, Andreas Faust, Sven Hermann, Friedemann Kiefer, Sabine Stötzer
    Project term: 10/2019 - 09/2024
    Project number: Innovative Medicines Initiative 2 Joint Undertaking, grant agreement No 831514

    Lymphatic vessel development in mouse embryo
    © EIMI

    Morphogenetic Mechanisms During Lymphatic Vessel Formation

    Lymphatic vessels are indispensable for tissue homeostasis and implicated in the development of several pathologies including edema, hypertension, chronic inflammation and tumour metastasis. Presently there is no pharmacological treatment for malfunctions of the lymphatic vessel system. Many regenerative processes would greatly benefit, if it were possible to stimulate and ensure proper lymph vessel formation. This requires a detailed understanding of the molecular regulation of their underlying morphogenetic mechanisms which we study here during mouse development.

    Principal investigators:  Friedemann Kiefer (EIMI)
    Project term: 01/2018 - 12/2021
    Project number: CRC/1348 B07 | DFG Collaborative Research Centre / 1348 “Dynamic Cellular Interfaces”

  • Team

  • Publications

    2025

    Kunisch M, Beutler S, Pilger C, Kiefer F, Huser T, Wirth B. Active axial motion compensation in multiphoton-excited fluorescence microscopy. Opt Express 2025;33: 3620-3636. Abstract
    Lupu I-E, Grainger DE, Kirschnick N, Weischer S, Zhao E, Martinez-Corral I, Schoofs H, Vanhollebeke M, Jones G, Godwin J, Forrow A, Lahmann I, Riley PR, Zobel T, Alitalo K, Makinen T, Kiefer F, Stone OA. Direct specification of lymphatic endothelium from mesenchymal progenitors. Nat Cardiovasc Res 2025;4: 45-63. Abstract

    2024

    Bauer N, Beckmann D, Reinhardt D, Frost N, Bobe S, Erapaneedi R, Risse B, Kiefer F. Therapy-induced modulation of tumor vasculature and oxygenation in a murine glioblastoma model quantified by deep learning-based feature extraction. Sci Rep 2024;14: 2034. Abstract
    Bauer N, Kiefer F. Genetically Encoded Reporters to Monitor Hypoxia. Methods Mol Biol 2024;2755: 3-29. Abstract
    Wen J, Pilger C, Wang W, Erapaneedi R, Xiu H, Fan Y, Hu X, Huser T, Kiefer F, Wei X, Yang Z. Watt-level all polarization-maintaining femtosecond fiber laser source at 1100  nm. Opt. Express 2024;32: 9625. Abstract

    2023

    Bauer N, Maisuls I, Pereira da Graca A, Reinhardt D, Erapaneedi R, Kirschnick N, Schäfers M, Grashoff C, Landfester K, Vestweber D, Strassert CA, Kiefer F. Genetically encoded dual fluorophore reporters for graded oxygen-sensing in light microscopy. Biosens Bioelectron 2023;221: 114917. Abstract
    Beckmann D, Kockwelp J, Gromoll J, Kiefer F, Risse B. SAM meets Gaze: Passive Eye Tracking for Prompt-based Instance Segmentation. NeuRIPS. 2023 Workshop on Gaze Meets ML 2023

    2022

    Bobe S, Beckmann D, Klump DM, Dierkes C, Kirschnick N, Redder E, Bauer N, Schäfers M, Erapaneedi R, Risse B, van de Pavert SA, Kiefer F. Volumetric imaging reveals VEGF-C-dependent formation of hepatic lymph vessels in mice. Front Cell Dev Biol 2022;10: 949896. Abstract
    Eliat F, Sohn R, Renner H, Kagermeier T, Volkery S, Brinkmann H, Kirschnick N, Kiefer F, Grabos M, Becker K, Bedzhov I, Schöler 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, Neudörfl 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
    Siret C, van Lessen M, Bavais J, Jeong HW, Reddy Samawar SK, Kapupara K, Wang S, Simic M, de Fabritus L, Tchoghandjian A, Fallet M, Huang H, Sarrazin S, Sieweke MH, Stumm R, Sorokin L, Adams RH, Schulte-Merker S, Kiefer F, van de Pavert SA. Deciphering the heterogeneity of the Lyve1(+) perivascular macrophages in the mouse brain. Nat Commun 2022;13: 7366. Abstract

    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, Lämmermann 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
    Drees D, Scherzinger A, Hägerling 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, Schäfers 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, Øie CI, Kirschnick N, Mönkemöller V, Hübner W, Förster C, Schüttpelz 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, Hägerling 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, Müschen M. Developmental partitioning of SYK and ZAP70 prevents autoimmunity and cancer. Mol Cell 2021;81: 2094-2111.e9. Abstract

    2020

    Macchi M, Magalon K, Zimmer C, Peeva E, El Waly B, Brousse B, Jaekel S, Grobe K, Kiefer F, Williams A, Cayre M, Durbec P. Mature oligodendrocytes bordering lesions limit demyelination and favor myelin repair via heparan sulfate production. Elife 2020;9: e51735. Abstract
    Martens R, Permanyer M, Werth K, Yu K, Braun A, Halle O, Halle S, Patzer GE, Bosnjak B, Kiefer F, Janssen A, Friedrichsen M, Poetzsch J, Kohli K, Lueder Y, Gutierrez Jauregui R, Eckert N, Worbs T, Galla M, Forster R. Efficient homing of T cells via afferent lymphatics requires mechanical arrest and integrin-supported chemokine guidance. Nat Commun 2020;11: 1114. Abstract

    2019

    Ghaffari A, Hoskin V, Turashvili G, Varma S, Mewburn J, Mullins G, Greer PA, Kiefer F, Day AG, Madarnas Y, SenGupta S, Elliott BE. Intravital imaging reveals systemic ezrin inhibition impedes cancer cell migration and lymph node metastasis in breast cancer. Breast Cancer Res 2019;21: 12. Abstract
    Hunter MC, Teijeira A, Montecchi R, Russo E, Runge P, Kiefer F, Halin C. Dendritic Cells and T Cells Interact Within Murine Afferent Lymphatic Capillaries. Front. Immunol. 2019;10: 11 pp. Abstract

    2018

    Bovay E, Sabine A, Prat-Luri B, Kim S, Son K, Willrodt A-H, Olsson C, Halin C, Kiefer F, Betsholtz C, Jeon NL, Luther SA, Petrova TV. Multiple roles of lymphatic vessels in peripheral lymph node development. J Exp Med 2018;215: 2760-2777. Abstract
    Dierkes C, Scherzinger A, Kiefer F. Three-Dimensional Visualization of the Lymphatic Vasculature. Methods Mol Biol 2018;1846: 1-18. Abstract
    Frye M, Taddei A, Dierkes C, Martinez-Corral I, Fielden M, Ortsater H, Kazenwadel J, Calado DP, Ostergaard P, Salminen M, He L, Harvey NL, Kiefer F, Makinen T. Matrix stiffness controls lymphatic vessel formation through regulation of a GATA2-dependent transcriptional program. Nat Commun 2018;9: 1511. Abstract
    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
    Lopez Tobon A, Suresh M, Jin J, Vitriolo A, Pietralla T, Tedford K, Bossenz M, Mahnken K, Kiefer F, Testa G, Fischer K-D, Puschel AW. The guanine nucleotide exchange factor Arhgef7/betaPix promotes axon formation upstream of TC10. Sci Rep 2018;8: 8811. Abstract
    Orlich M, Kiefer F. A qualitative comparison of ten tissue clearing techniques. Histol Histopathol 2018;33: 181-199. Abstract
    Seifert R, Kuhlmann MT, Eligehausen S, Kiefer F, Hermann S, Schafers M. Molecular imaging of MMP activity discriminates unstable from stable plaque phenotypes in shear-stress induced murine atherosclerosis. PLoS One 2018;13: e0204305. Abstract

    2017

    Hägerling R, Drees D, Scherzinger A, Dierkes C, Martin-Almedina S, Butz S, Gordon K, Schäfers 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
    Karpanen T, Padberg Y, van de Pavert SA, Dierkes C, Morooka N, Peterson-Maduro J, van de Hoek G, Adrian M, Mochizuki N, Sekiguchi K, Kiefer F, Schulte D, Schulte-Merker S. An Evolutionarily Conserved Role for Polydom/Svep1 During Lymphatic Vessel Formation. Circ Res 2017;120: 1263-1275. Abstract
    Seifert R, Scherzinger A, Kiefer F, Hermann S, Jiang X, Schafers MA. Statistical Permutation-based Artery Mapping (SPAM): a novel approach to evaluate imaging signals in the vessel wall. BMC Med Imaging 2017;17: 36. Abstract
    Weis V, Konigsberger S, Amler S, Wienands J, Kiefer F. Unperturbed Immune Function despite Mutation of C-Terminal Tyrosines in Syk Previously Implicated in Signaling and Activity Regulation. Mol Cell Biol 2017;37Abstract

    2016

    Erapaneedi R, Belousov VV, Schäfers 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
    Scherzinger A, Kleene F, Dierkes C, Kiefer F, Hinrichs K, Jiang X. Automated Segmentation of Immunostained Cell Nuclei in 3D Ultramicroscopy Images. In: Pattern Recognition - 38th German Conference, GCPR 2016, Hannover, Germany, Sept. 12-15, 2016;Springer: 105-116. Abstract

    2015

    Bălan M, Kiefer F. A novel model for ectopic, chronic, intravital multiphoton imaging of bone marrow vasculature and architecture in split femurs. IntraVital 2015;4: e1066949. Abstract
    Helker CSM, Schuermann A, Pollmann C, Chng SC, Kiefer F, Reversade B, Herzog W. The hormonal peptide Elabela guides angioblasts to the midline during vasculogenesis. Elife 2015;4: e06726. Abstract

    2014

    Born G, Breuer D, Wang S, Rohlmann A, Coulon P, Vakili P, Reissner C, Kiefer F, Heine M, Pape H-C, Missler M. Modulation of synaptic function through the alpha-neurexin-specific ligand neurexophilin-1. Proc Natl Acad Sci U S A 2014;111: E1274-83. Abstract
    D'Amico G, Korhonen EA, Anisimov A, Zarkada G, Holopainen T, Hägerling R, Kiefer F, Eklund L, Sormunen R, Elamaa H, Brekken RA, Adams RH, Koh GY, Saharinen P, Alitalo K. Tie1 deletion inhibits tumor growth and improves angiopoietin antagonist therapy. J Clin Invest 2014;124: 824-834. Abstract
    Dartsch N, Schulte D, Hägerling R, Kiefer F, Vestweber D. Fusing VE-Cadherin to alpha-Catenin Impairs Fetal Liver Hematopoiesis and Lymph but Not Blood Vessel Formation. Mol Cell Biol 2014;34: 1634-1648. Abstract
    Pollmann C, Hägerling R, Kiefer F. Visualization of lymphatic vessel development, growth, and function. Adv Anat Embryol Cell Biol 2014;214: 167-186. 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
    Pollmann C, Hägerling R, Andreas M, Kiefer F. Ultramikroskopische Darstellung von Lymphgefäßen während der Fötalentwicklung und im Erwachsenenstadium der Maus. LymphForsch 2013;17: 6-12.
    Wang L, Benedito R, Bixel MG, Zeuschner D, Stehling M, Savendahl L, Haigh JJ, Snippert H, Clevers H, Breier G, Kiefer F, Adams RH. Identification of a clonally expanding haematopoietic compartment in bone marrow. EMBO J 2013;32: 219-230. Abstract

    2012

    Königsberger S, Prodöhl J, Stegner D, Weis V, Andreas M, Stehling M, Schumacher T, Böhmer R, Thielmann I, van Eeuwijk JMM, Nieswandt B, Kiefer F. Altered BCR signalling quality predisposes to autoimmune disease and a pre-diabetic state. EMBO J 2012;31: 3363-3374. Abstract
    Sabine A, Agalarov Y, Maby-El Hajjami H, Jaquet M, Hägerling R, Pollmann C,Bebber D, Pfenniger A, Miura N, Dormond O, Calmes JM, Adams RH, Mäkinen T, Kiefer F, Kwak BR, Petrova TV. Mechanotransduction, PROX1, and FOXC2 Cooperate to Control Connexin37 and Calcineurin during Lymphatic-Valve Formation. Dev Cell 2012: 430-45. Abstract

    2011

    Hägerling R, Pollmann C, Kremer L, Andresen V, Kiefer F. Intravital two-photon microscopy of lymphatic vessel development and function using a transgenic Prox1 promoter-directed mOrange2 reporter mouse. Biochem Soc Trans 2011;39: 1674-1681. Abstract
    Kiefer F, Siekmann AF. The role of chemokines and their receptors in angiogenesis. Cell Mol Life Sci 2011;68: 2811-2830. Abstract
    Neuhaus B, Buhren S, Bock B, Alves F, Vogel WF, Kiefer F. Migration inhibition of mammary epithelial cells by Syk is blocked in the presence of DDR1 receptors. Cell Mol Life Sci 2011;68: 3757-70. Abstract
    Schulte D, Kuppers V, Dartsch N, Broermann A, Li H, Zarbock A, Kamenyeva O, Kiefer F, Khandoga A, Massberg S, Vestweber D. Stabilizing the VE-cadherin-catenin complex blocks leukocyte extravasation and vascular permeability. EMBO J 2011: 4157-70. Abstract

    2010

    Böhmer R, Neuhaus B, Bühren S, Zhang D, Stehling M, Böck B, Kiefer F. Regulation of developmental lymphangiogenesis by Syk(+) leukocytes. Dev Cell 2010;18: 437-449. Abstract
    Patzak IM, Königsberger S, Suzuki A, Mak TW, Kiefer F. HPK1 competes with ADAP for SLP-76 binding and via Rap1 negatively affects T-cell adhesion. Eur J Immunol 2010;40: 3220-3225. Abstract

    2009

    Winderlich M, Keller L, Cagna G, Broermann A, Kamenyeva O, Kiefer F, Deutsch U, Nottebaum AF, Vestweber D. VE-PTP controls blood vessel development by balancing Tie-2 activity. J Cell Biol 2009;185: 657-671. Abstract

    2007

    Arnold R, Frey CR, Muller W, Brenner D, Krammer PH, Kiefer F. Sustained JNK signaling by proteolytically processed HPK1 mediates IL-3 independent survival during monocytic differentiation. Cell Death Differ 2007;14: 568-575. Abstract

    2005

    Arnold R, Patzak IM, Neuhaus B, Vancauwenbergh S, Veillette A, Van Lint J, Kiefer F. Activation of hematopoietic progenitor kinase 1 involves relocation, autophosphorylation, and transphosphorylation by protein kinase D1. Mol Cell Biol 2005;25: 2364-2383. Abstract