A02

Mechanisms of vascular Wnt signaling during liver homeostasis and tumorigenesis

Funding period: 2017-2025

Project Leaders

Prof. Dr. Hellmut G. Augustin

Project Leader A02

Abstract

Wnt signaling controls growth, maturation and remodeling of blood vessels. Moreover, vascular cell-derived Wnt signals exert regulatory functions on their microenvironment in a paracrine (angiocrine) manner. The liver has become a model organ for the study of angiocrine signaling mechanisms. Recently, a high-resolution map of liver endothelial cell signaling was established and the Tie receptor was identified as a specific and selective regulator of liver vascular Wnt ligand production and signaling. Based on this work, the role of vascular Wnt signaling in regulating the crosstalk between endothelial cells and hepatocytes will be analyzed, during homeostasis and pathological challenges, including tumor growth.

Project-related Publications

A spatial vascular transcriptomic, proteomic, and phosphoproteomic atlas unveils an angiocrine Tie–Wnt signaling axis in the liver

Inverso D, Shi J, Lee KH, Jakab M, Ben-Moshe S, Kulkarni SR, Schneider M, Wang G, Komeili M, Vélez PA, Riedel M, Spegg C, Ruppert T, Schaeffer-Reiss C, Helm D, Singh I, Boutros M, Chintharlapalli S, Heikenwalder M, Itzkovitz S, Augustin HG. Dev Cell. 2021 Jun 7;56(11):1677-1693.e10. PMID: 34038707

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Understanding angiodiversity: Insights from single cell biology

Jakab M, Augustin HG. Development. 2020 Aug 12;147(15):dev146621. doi: 10.1242/dev.146621. PMID: 32792338

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Tumor cell-derived Angiopoietin-2 promotes metastasis in melanoma

Abdul Pari AA, Singhal M, Hübers C, Mogler C, Schieb B, Gampp A, Gengenbacher N, Reynolds LE, Terhardt D, Géraud C, Utikal J, Thomas M, Goerdt S, Hodivala-Dilke KM, Augustin HG#, Felcht M.# Cancer Res. 2020 Jun 15;80(12):2586-2598. doi: 10.1158/0008-5472.CAN-19-2660. Epub 2020 Apr 17. (#equally contributing last authors) PMID: 32303578

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Preclinical validation of a novelmetastasis inhibiting Tie1 function-blocking antibody

Singhal M, Gengenbacher N, La Porta S, Gehrs S, Shi J, Kamiyama M, Bodenmiller DM, Fischl A, Schieb B, Besemfelder E, Chintharlapalli S, Augustin HG. EMBO Mol Med. 2020 Jun 8;12(6):e11164. doi: 10.15252/emmm.201911164. Epub 2020 Apr 17. PMID: 32302470

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Endothelial cell fitness dictates the source of regenerating liver vasculature

Singhal, M.#, X. Liu#, D. Inverso, K. Jiang, J. Dai, H. He, S. Bartels, W. Li, A.A. Abdul Pari, N. Gengenbacher, E. Besemfelder, L. Hui, H.G. Augustin§, J. Hu§. J Exp Med. 2018 Oct 1;215(10):2497-2508. doi: 10.1084/jem.20180008. Epub 2018 Sep 7. (#equally contributing first authors; §equally contributing senior authors). PMID: 30194265.

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The transcriptomic and epigenetic map of vascular quiescence in the continuous lung endothelium

Schlereth K, Weichenhan D, Bauer T, Heumann T, Giannakouri E, Lipka D, Jaeger S, Schlesner M, Aloy P, Eils R, Plass C, Augustin HG. Elife. 2018 May 11;7. PMID:29749927

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