Lymphovaskuläre Medizin und Translationale 3D-Histopathologie

We develop and implement novel methods for three-dimensional tissue analysis, enabling unprecedented insights into tissue architecture and disease mechanisms through the integration of spatial information with multi-omics data.

Key Research Areas:

• Development of tissue clearing and bleaching protocols
• Light sheet microscopy-based optical sectioning
• AI-powered 3D tissue analysis
• Real-time organoid imaging
• Spatial multi-omics integration
• Deep tissue phenotyping

Technology Platforms:

• Nanobody-based Tissue Staining Protocols
• Light sheet microscopy
• AI-based image analysis
• High-throughput screening systems

PRessemitteilung One million euros for histology in 3D

We leverage our multi-modal diagnostic approach to advance cancer diagnosis and treatment, combining spatial information with molecular profiles.

Key Research Areas:

• Multi-dimensional tumor analysis
• Integration of genomics and 3D-histology
• Development of novel diagnostic workflows
• AI-driven pattern recognition
• Liquid biopsy approaches
• Patient Stratification

Key Research Areas:

• Novel Nanobody Screening Platform
• Reversible, multiplex Stainings (>20 markers)
• Diagnostic Imaging Tools
• Targeted therapeutic approaches

Applications:

• 3D-Histology and Molecular Imaging
• Diagnostic Markers
• Nanobodies for therapeutic interventions

Our group specializes in the diagnosis and treatment of vascular anomalies, developing innovative approaches to improve patient care through comprehensive molecular and imaging diagnostics. We focus on translating research findings into targeted therapeutic strategies for these rare conditions.

Key Research Areas:

• Genetic basis of vascular anomalies
• Lymphatic malformation mechanisms
• Gene therapy approaches
• Biomarker development
• Clinical phenotyping
• Organoid and Mouse models
• ICG Lymphography
• Patient Stratification
• Molecular Diagnostic test development
• Liquid Biopsies
• Whole Genome Sequencing

Our specialized clinics serve as central reference centers for patients with rare vascular diseases, providing comprehensive care through (Clinical Integration):

• Expert consultation for complex cases
• Advanced diagnostic services
• Personalized therapy approaches
• International patient registry
• Multi-disciplinary treatment strategies

Core Technologies

• Light sheet microscopy
• 3D tissue clearing
• Nanobody development platform
• AI-powered image analysis
• Liquid Biopsies
• Whole Genome Sequencing
• High-throughput screening

Method Development

• Novel tissue clearing protocols
• Automated sample preparation
• AI-based analysis pipelines
• Nanobody modification techniques
• Integrative data analysis workflows
• Molecular diagnostic development (liquid Biopsy)

Group Leader

Dr. Dr. René Hägerling, MD PhD

• Board-certified Human Geneticist
• President, Deutsche Gesellschaft für Lymphologie
• Spokesman Section Lymphology, Deutsche Gesellschaft für Phlebologie und Lymphologie
• Founding Member, International Lipedema Association
• Co-Founder LIMAA Technologies GmbH

Clinical Team ‘Lymphovascular Medicine’

• Sarina Schwartzmann, Registrar Human Genetics, MD
• Magdalena Danyel, board-certified Human Geneticist, Clinician Scientist MD
• Charlotte Kemper, Registrar Human Genetics, MD

Research Group

• Rose Behncke, M.Sc., PhD Student
• Dr. Nils Hansmeier, Postdoc
• Abhimanyu Singh, M.Sc., PhD student
• Sascha Ulferts, Bio-technician
• Lea Amina Kalayci, M.Sc., PhD Student
• Valentin Fabricius, M.Sc., MD student
• Eva-Maria Funk, MD student
• Ina Büschlen, MD student
• Ines Grigorova, MD student
• Lea Rissmann, MD student

Huang X, Henck J, Qiu C, Sreenivasan VKA, Balachandran S, Amarie OV, Hrabě de Angelis M, Behncke RY, Chan WL, Despang A, Dickel DE, Duran M, Feuchtinger A, Fuchs H, Gailus-Durner V, Haag N, Hägerling R, Hansmeier N, Hennig F, Marshall C, Rajderkar S, Ringel A, Robson M, Saunders LM, da Silva-Buttkus P, Spielmann N, Srivatsan SR, Ulferts S, Wittler L, Zhu Y, Kalscheuer VM, Ibrahim DM, Kurth I, Kornak U, Visel A, Pennacchio LA, Beier DR, Trapnell C, Cao J, Shendure J, Spielmann M. Single-cell, whole-embryo phenotyping of mammalian developmental disorders. Nature. 2023 Nov;623(7988):772-781. doi: 10.1038/s41586-023-06548-w. Epub 2023 Nov 15. PMID: 37968388; PMCID: PMC10665194.

Heron C, Dumesnil A, Houssari M, Renet S, Lemarcis T, Lebon A, Godefroy D, Schapman D, Henri O, Riou G, Nicol L, Henry JP, Valet M, Pieronne-Deperrois M, Ouvrard-Pascaud A, Hagerling R, Chiavelli H, Michel JB, Mulder P, Fraineau S, Richard V, Tardif V, Brakenhielm E. Regulation and impact of cardiac lymphangiogenesis in pressure-overload-induced heart failure. Cardiovasc Res. 2023 Mar 31;119(2):492-505. doi: 10.1093/cvr/cvac086. PMID: 35689481; PMCID: PMC10064842.

Hägerling R, Van Zanten M, Behncke RY, Ulferts S, Hansmeier NR, Märkl B, Witzel C, Ho B, Keeley V, Riches K, Mansour S, Gordon K, Ostergaard P, Mortimer PS. Erythematous capillary-lymphatic malformations mimicking blood vascular anomalies. JCI Insight. 2023 Oct 23;8(20):e172179. doi: 10.1172/jci.insight.172179. PMID: 37698920; PMCID: PMC10619487.

Cornely M, Hägerling R. Lymphologie und Dermatologie : Warum sollten diese beiden Fachbereiche der Medizin in einem Leitthemenheft gewürdigt werden? [Lymphology and dermatology : Why should these two medical specialties be honored in a special issue?]. Dermatologie (Heidelb). 2023 Aug;74(8):563-565. German. doi: 10.1007/s00105-023-05190-x. Epub 2023 Jul 24. PMID: 37486384.

Hägerling R. Genetik, Diagnostik und Klinik des primären Lymphödems [Genetics, diagnostics and clinical presentation of primary lymphoedema]. Dermatologie (Heidelb). 2023 Aug;74(8):594-604. German. doi: 10.1007/s00105-023-05183-w. Epub 2023 Jul 4. PMID: 37402871.

Hramyka D, Sczakiel HL, Zhao MX, Stolpe O, Nieminen M, Adam R, Danyel M, Einicke L, Hägerling R, Knaus A, Mundlos S, Schwartzmann S, Seelow D, Ehmke N, Mensah MA, Boschann F, Beule D, Holtgrewe M. REEV: review, evaluate and explain variants. Nucleic Acids Res. 2024 Jul 5;52(W1):W148-W158. doi: 10.1093/nar/gkae366. PMID: 38769069; PMCID: PMC11223839.

Lampejo AO, Ghavimi SAA, Hägerling R, Agarwal S, Murfee WL. Lymphatic/blood vessel plasticity: motivation for a future research area based on present and past observations. Am J Physiol Heart Circ Physiol. 2023 Jan 1;324(1):H109-H121. doi: 10.1152/ajpheart.00612.2022. Epub 2022 Dec 2. PMID: 36459445; PMCID: PMC9829479.

Freise L, Behncke RY, Allerkamp HH, Sandermann TH, Chu NH, Funk EM, Hondrich LJ, Riedel A, Witzel C, Hansmeier NR, Danyel M, Gellhaus A, Dechend R, Hägerling R. Three-Dimensional Histological Characterization of the Placental Vasculature Using Light Sheet Microscopy. Biomolecules. 2023 Jun 17;13(6):1009. doi: 10.3390/biom13061009. PMID: 37371590; PMCID: PMC10296419.

Boschann F, Cogulu O, Pehlivan D, Balachandran S, Vallecillo-Garcia P, Grochowski CM, Hansmeier NR, Coban Akdemir ZH, Prada-Medina CA, Aykut A, Fischer-Zirnsak B, Badura S, Durmaz B, Ozkinay F, Hägerling R, Posey JE, Stricker S, Gillessen-Kaesbach G, Spielmann M, Horn D, Brockmann K, Lupski JR, Kornak U, Schmidt J. Biallelic variants in ADAMTS15 cause a novel form of distal arthrogryposis. Genet Med. 2023 May;25(5):100799. doi: 10.1016/j.gim.2023.100799. Epub 2023 Feb 28. Erratum for: Genet Med. 2022 Oct;24(10):2187-2193. doi: 10.1016/j.gim.2022.07.012. PMID: 36853234.

Boschann F, Cogulu MÖ, Pehlivan D, Balachandran S, Vallecillo-Garcia P, Grochowski CM, Hansmeier NR, Coban Akdemir ZH, Prada-Medina CA, Aykut A, Fischer-Zirnsak B, Badura S, Durmaz B, Ozkinay F, Hägerling R, Posey JE, Stricker S, Gillessen-Kaesbach G, Spielmann M, Horn D, Brockmann K, Lupski JR, Kornak U, Schmidt J. Biallelic variants in ADAMTS15 cause a novel form of distal arthrogryposis. Genet Med. 2022 Oct;24(10):2187-2193. doi: 10.1016/j.gim.2022.07.012. Epub 2022 Aug 13. Erratum in: Genet Med. 2023 May;25(5):100799. doi: 10.1016/j.gim.2023.100799. PMID: 35962790; PMCID: PMC9982667.

Vallecillo-García P, Kühnlein MN, Orgeur M, Hansmeier NR, Kotsaris G, Meisen ZG, Timmermann B, Giesecke-Thiel C, Hägerling R, Stricker S. Mesenchymal Osr1+ cells regulate embryonic lymphatic vessel formation. Development. 2024 Sep 1;151(17):dev202747. doi: 10.1242/dev.202747. Epub 2024 Sep 2. PMID: 39221968; PMCID: PMC11441984.

Hansmeier NR, Büschlen IS, Behncke RY, Ulferts S, Bisoendial R, Hägerling R. 3D Visualization of Human Blood Vascular Networks Using Single-Domain Antibodies Directed against Endothelial Cell-Selective Adhesion Molecule (ESAM). Int J Mol Sci. 2022 Apr 15;23(8):4369. doi: 10.3390/ijms23084369. PMID: 35457187; PMCID: PMC9028812.