{"entity": "researcher", "timestamp": "2026-08-23T10:13:02.856Z", "family": "Claesson-Welsh", "given": "Lena", "initials": "L", "orcid": "0000-0003-4275-2000", "affiliations": ["Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/6b07fbf00dad4ac8a4a53402888d55ef.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/6b07fbf00dad4ac8a4a53402888d55ef"}}, "publications": [{"entity": "publication", "iuid": "a956e9d3498543299d484573e3f2c29e", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/a956e9d3498543299d484573e3f2c29e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/a956e9d3498543299d484573e3f2c29e"}}, "title": "VE-cadherin junction dynamics in initial lymphatic vessels promotes lymph node metastasis.", "authors": [{"family": "S\u00e1inz-Jaspeado", "given": "Miguel", "initials": "M"}, {"family": "Ring", "given": "Sarah", "initials": "S"}, {"family": "Proulx", "given": "Steven T", "initials": "ST"}, {"family": "Richards", "given": "Mark", "initials": "M"}, {"family": "Martinsson", "given": "Pernilla", "initials": "P"}, {"family": "Li", "given": "Xiujuan", "initials": "X"}, {"family": "Claesson-Welsh", "given": "Lena", "initials": "L", "orcid": "0000-0003-4275-2000", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6b07fbf00dad4ac8a4a53402888d55ef.json"}}, {"family": "Ulvmar", "given": "Maria H", "initials": "MH", "orcid": "0000-0002-9050-0978", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/081a6551b7b94c36b059410b02f25133.json"}}, {"family": "Jin", "given": "Yi", "initials": "Y", "orcid": "0000-0001-9704-973X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/69ee4790c8f24da08ba6cf7759d254db.json"}}], "type": "journal article", "published": "2024-03-00", "journal": {"title": "Life Sci. Alliance", "issn": "2575-1077", "volume": "7", "issue": "3", "issn-l": null}, "abstract": "The endothelial junction component vascular endothelial (VE)-cadherin governs junctional dynamics in the blood and lymphatic vasculature. Here, we explored how lymphatic junction stability is modulated by elevated VEGFA signaling to facilitate metastasis to sentinel lymph nodes. Zippering of VE-cadherin junctions was established in dermal initial lymphatic vessels after VEGFA injection and in tumor-proximal lymphatics in mice. Shape analysis of pan-cellular VE-cadherin fragments revealed that junctional zippering was accompanied by accumulation of small round-shaped VE-cadherin fragments in the lymphatic endothelium. In mice expressing a mutant VEGFR2 lacking the Y949 phosphosite (Vegfr2 ) required for activation of Src family kinases, zippering of lymphatic junctions persisted, whereas accumulation of small VE-cadherin fragments was suppressed. Moreover, tumor cell entry into initial lymphatic vessels and subsequent metastatic spread to lymph nodes was reduced in mutant mice compared with WT, after challenge with B16F10 melanoma or EO771 breast cancer. We conclude that VEGFA mediates zippering of VE-cadherin junctions in initial lymphatics. Zippering is accompanied by increased VE-cadherin fragmentation through VEGFA-induced Src kinase activation, correlating with tumor dissemination to sentinel lymph nodes.Y949F/Y949F", "doi": "10.26508/lsa.202302168", "pmid": "38148112", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10751244"}, {"db": "pii", "key": "7/3/e202302168"}], "notes": [], "created": "2026-08-21T12:56:26.546Z", "modified": "2026-08-21T12:56:26.626Z"}, {"entity": "publication", "iuid": "2d0268c3a5a9452e862dc7f4cf92be76", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/2d0268c3a5a9452e862dc7f4cf92be76.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/2d0268c3a5a9452e862dc7f4cf92be76"}}, "title": "Chylomicrons Regulate Lacteal Permeability and Intestinal Lipid Absorption.", "authors": [{"family": "Zarkada", "given": "Georgia", "initials": "G"}, {"family": "Chen", "given": "Xun", "initials": "X"}, {"family": "Zhou", "given": "Xuetong", "initials": "X"}, {"family": "Lange", "given": "Martin", "initials": "M", "orcid": "0009-0001-1798-3520", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3412b012bea54ed58d984f1a651195da.json"}}, {"family": "Zeng", "given": "Lei", "initials": "L"}, {"family": "Lv", "given": "Wenyu", "initials": "W", "orcid": "0009-0002-2523-448X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/461e580db5ca4546937e7082c948ac8f.json"}}, {"family": "Zhang", "given": "Xuan", "initials": "X"}, {"family": "Li", "given": "Yunhua", "initials": "Y"}, {"family": "Zhou", "given": "Weibin", "initials": "W"}, {"family": "Liu", "given": "Keli", "initials": "K"}, {"family": "Chen", "given": "Dongying", "initials": "D"}, {"family": "Ricard", "given": "Nicolas", "initials": "N", "orcid": "0000-0002-7572-173X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/79dc478ceaea44e886a3bc2c3275ea72.json"}}, {"family": "Liao", "given": "James", "initials": "J", "orcid": "0000-0001-9679-4252", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c6d7214cd4df43f4a748ac79a9e42e11.json"}}, {"family": "Kim", "given": "Young-Bum", "initials": "YB", "orcid": "0000-0001-9471-6330", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6c4d981679344ada8535b0bdc854ca12.json"}}, {"family": "Benedito", "given": "Rui", "initials": "R"}, {"family": "Claesson-Welsh", "given": "Lena", "initials": "L", "orcid": "0000-0003-4275-2000", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6b07fbf00dad4ac8a4a53402888d55ef.json"}}, {"family": "Alitalo", "given": "Kari", "initials": "K", "orcid": "0000-0002-7331-0902", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/d9a1a31264694e4fba6026b293655ff0.json"}}, {"family": "Simons", "given": "Michael", "initials": "M", "orcid": "0000-0003-0348-7734", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/39eb33a1709349e897bddeab1ccdb1ae.json"}}, {"family": "Ju", "given": "Rong", "initials": "R"}, {"family": "Li", "given": "Xuri", "initials": "X"}, {"family": "Eichmann", "given": "Anne", "initials": "A", "orcid": "0000-0001-5563-210X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c54a01fdba19484d8ab0bb594774f909.json"}}, {"family": "Zhang", "given": "Feng", "initials": "F", "orcid": "0000-0002-6103-1498", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8d634b6556574ea3bd8ffbf83f9a7303.json"}}], "type": "journal article", "published": "2023-08-04", "journal": {"title": "Circ. Res.", "issn": "1524-4571", "volume": "133", "issue": "4", "pages": "333-349", "issn-l": "0009-7330"}, "abstract": "Lymphatic vessels are responsible for tissue drainage, and their malfunction is associated with chronic diseases. Lymph uptake occurs via specialized open cell-cell junctions between capillary lymphatic endothelial cells (LECs), whereas closed junctions in collecting LECs prevent lymph leakage. LEC junctions are known to dynamically remodel in development and disease, but how lymphatic permeability is regulated remains poorly understood.\n\nWe used various genetically engineered mouse models in combination with cellular, biochemical, and molecular biology approaches to elucidate the signaling pathways regulating junction morphology and function in lymphatic capillaries.\n\nBy studying the permeability of intestinal lacteal capillaries to lipoprotein particles known as chylomicrons, we show that ROCK (Rho-associated kinase)-dependent cytoskeletal contractility is a fundamental mechanism of LEC permeability regulation. We show that chylomicron-derived lipids trigger neonatal lacteal junction opening via ROCK-dependent contraction of junction-anchored stress fibers. LEC-specific ROCK deletion abolished junction opening and plasma lipid uptake. Chylomicrons additionally inhibited VEGF (vascular endothelial growth factor)-A signaling. We show that VEGF-A antagonizes LEC junction opening via VEGFR (VEGF receptor) 2 and VEGFR3-dependent PI3K (phosphatidylinositol 3-kinase)/AKT (protein kinase B) activation of the small GTPase RAC1 (Rac family small GTPase 1), thereby restricting RhoA (Ras homolog family member A)/ROCK-mediated cytoskeleton contraction.\n\nOur results reveal that antagonistic inputs into ROCK-dependent cytoskeleton contractions regulate the interconversion of lymphatic junctions in the intestine and in other tissues, providing a tunable mechanism to control the lymphatic barrier.", "doi": "10.1161/CIRCRESAHA.123.322607", "pmid": "37462027", "labels": [], "xrefs": [{"db": "mid", "key": "NIHMS1915517"}, {"db": "pmc", "key": "PMC10530007"}], "notes": [], "created": "2026-08-21T12:31:09.955Z", "modified": "2026-08-21T12:31:10.400Z"}, {"entity": "publication", "iuid": "96b2e139a15a412fb34c6e7215c17e8f", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/96b2e139a15a412fb34c6e7215c17e8f.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/96b2e139a15a412fb34c6e7215c17e8f"}}, "title": "Paladin is a phosphoinositide phosphatase regulating endosomal VEGFR2 signalling and angiogenesis.", "authors": [{"family": "Nitzsche", "given": "Anja", "initials": "A", "orcid": "0000-0003-0567-6790", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/595648a7cd814572bc508aad4514310d.json"}}, {"family": "Pietil\u00e4", "given": "Riikka", "initials": "R"}, {"family": "Love", "given": "Dominic T", "initials": "DT"}, {"family": "Testini", "given": "Chiara", "initials": "C"}, {"family": "Ninchoji", "given": "Takeshi", "initials": "T"}, {"family": "Smith", "given": "Ross O", "initials": "RO"}, {"family": "Ekv\u00e4rn", "given": "Elisabet", "initials": "E"}, {"family": "Larsson", "given": "Jimmy", "initials": "J"}, {"family": "Roche", "given": "Francis P", "initials": "FP"}, {"family": "Ega\u00f1a", "given": "Isabel", "initials": "I"}, {"family": "Jauhiainen", "given": "Suvi", "initials": "S"}, {"family": "Berger", "given": "Philipp", "initials": "P"}, {"family": "Claesson-Welsh", "given": "Lena", "initials": "L", "orcid": "0000-0003-4275-2000", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6b07fbf00dad4ac8a4a53402888d55ef.json"}}, {"family": "Hellstr\u00f6m", "given": "Mats", "initials": "M", "orcid": "0000-0002-7088-9533", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f4a3452ee3f54ec7bc33e92b9f1a6374.json"}}], "type": "journal article", "published": "2021-02-03", "journal": {"title": "EMBO Rep.", "issn": "1469-3178", "volume": "22", "issue": "2", "pages": "e50218", "issn-l": "1469-221X"}, "abstract": "Cell signalling governs cellular behaviour and is therefore subject to tight spatiotemporal regulation. Signalling output is modulated by specialized cell membranes and vesicles which contain unique combinations of lipids and proteins. The phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2 ), an important component of the plasma membrane as well as other subcellular membranes, is involved in multiple processes, including signalling. However, which enzymes control the turnover of non-plasma membrane PI(4,5)P2 , and their impact on cell signalling and function at the organismal level are unknown. Here, we identify Paladin as a vascular PI(4,5)P2 phosphatase regulating VEGFR2 endosomal signalling and angiogenesis. Paladin is localized to endosomal and Golgi compartments and interacts with vascular endothelial growth factor receptor 2 (VEGFR2) in vitro and in vivo. Loss of Paladin results in increased internalization of VEGFR2, over-activation of extracellular regulated kinase 1/2, and hypersprouting of endothelial cells in the developing retina of mice. These findings suggest that inhibition of Paladin, or other endosomal PI(4,5)P2 phosphatases, could be exploited to modulate VEGFR2 signalling and angiogenesis, when direct and full inhibition of the receptor is undesirable.", "doi": "10.15252/embr.202050218", "pmid": "33369848", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7857541"}], "notes": [], "created": "2026-08-21T12:53:55.724Z", "modified": "2026-08-21T12:53:55.822Z"}, {"entity": "publication", "iuid": "2d862b2b319c4ca798556d74ee34f863", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/2d862b2b319c4ca798556d74ee34f863.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/2d862b2b319c4ca798556d74ee34f863"}}, "title": "Vascular permeability in retinopathy is regulated by VEGFR2 Y949 signaling to VE-cadherin.", "authors": [{"family": "Smith", "given": "Ross O", "initials": "RO", "orcid": "0000-0003-4239-3204", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f597e3f2a2a142c5b0dc7e1559f800b7.json"}}, {"family": "Ninchoji", "given": "Takeshi", "initials": "T"}, {"family": "Gordon", "given": "Emma", "initials": "E"}, {"family": "Andr\u00e9", "given": "Helder", "initials": "H"}, {"family": "Dejana", "given": "Elisabetta", "initials": "E"}, {"family": "Vestweber", "given": "Dietmar", "initials": "D", "orcid": "0000-0002-3517-732X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5f301c4b5e7f44e5beda910d49315c50.json"}}, {"family": "Kvanta", "given": "Anders", "initials": "A"}, {"family": "Claesson-Welsh", "given": "Lena", "initials": "L", "orcid": "0000-0003-4275-2000", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6b07fbf00dad4ac8a4a53402888d55ef.json"}}], "type": "journal article", "published": "2020-04-21", "journal": {"title": "Elife", "issn": "2050-084X", "volume": "9", "issn-l": "2050-084X"}, "abstract": "Edema stemming from leaky blood vessels is common in eye diseases such as age-related macular degeneration and diabetic retinopathy. Whereas therapies targeting vascular endothelial growth factor A (VEGFA) can suppress leakage, side-effects include vascular rarefaction and geographic atrophy. By challenging mouse models representing different steps in VEGFA/VEGF receptor 2 (VEGFR2)-induced vascular permeability, we show that targeting signaling downstream of VEGFR2 pY949 limits vascular permeability in retinopathy induced by high oxygen or by laser-wounding. Although suppressed permeability is accompanied by reduced pathological neoangiogenesis in oxygen-induced retinopathy, similarly sized lesions leak less in mutant mice, separating regulation of permeability from angiogenesis. Strikingly, vascular endothelial (VE)-cadherin phosphorylation at the Y685, but not Y658, residue is reduced when VEGFR2 pY949 signaling is impaired. These findings support a mechanism whereby VE-cadherin Y685 phosphorylation is selectively associated with excessive vascular leakage. Therapeutically, targeting VEGFR2-regulated VE-cadherin phosphorylation could suppress edema while leaving other VEGFR2-dependent functions intact.", "doi": "10.7554/eLife.54056", "pmid": "32312382", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7188482"}, {"db": "pii", "key": "54056"}], "notes": [], "created": "2026-08-21T13:07:32.230Z", "modified": "2026-08-21T13:07:32.366Z"}, {"entity": "publication", "iuid": "94df37cc799b45b790d134c3007f01d5", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/94df37cc799b45b790d134c3007f01d5.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/94df37cc799b45b790d134c3007f01d5"}}, "title": "Perivascular Neuropilin-1 expression is an independent marker of improved survival in renal cell carcinoma.", "authors": [{"family": "Morin", "given": "Eric", "initials": "E", "orcid": "0000-0002-0578-4516", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c4596240d0994f5db874350ff04332b8.json"}}, {"family": "Lindskog", "given": "Cecilia", "initials": "C"}, {"family": "Johansson", "given": "Martin", "initials": "M", "orcid": "0000-0001-8510-3102", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f255d8b3d7754dc7aa2a9604c431f4e3.json"}}, {"family": "Egevad", "given": "Lars", "initials": "L"}, {"family": "Sandstr\u00f6m", "given": "Per", "initials": "P"}, {"family": "Harmenberg", "given": "Ulrika", "initials": "U"}, {"family": "Claesson-Welsh", "given": "Lena", "initials": "L", "orcid": "0000-0003-4275-2000", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6b07fbf00dad4ac8a4a53402888d55ef.json"}}, {"family": "Sj\u00f6berg", "given": "Elin", "initials": "E"}], "type": "journal article", "published": "2020-04-00", "journal": {"title": "J. Pathol.", "issn": "1096-9896", "volume": "250", "issue": "4", "pages": "387-396", "issn-l": "0022-3417"}, "abstract": "Renal cell carcinoma (RCC) treatment has improved in the last decade with the introduction of drugs targeting tumor angiogenesis. However, the 5-year survival of metastatic disease is still only 10-15%. Here, we explored the prognostic significance of compartment-specific expression of Neuropilin 1 (NRP1), a co-receptor for vascular endothelial growth factor (VEGF). NRP1 expression was analyzed in RCC tumor vessels, in perivascular tumor cells, and generally in the tumor cell compartment. Moreover, complex formation between NRP1 and the main VEGF receptor, VEGFR2, was determined. Two RCC tissue microarrays were used; a discovery cohort consisting of 64 patients and a validation cohort of 314 patients. VEGFR2/NRP1 complex formation in cis (on the same cell) and trans (between cells) configurations was determined by in situ proximity ligation assay (PLA), and NRP1 protein expression in three compartments (endothelial cells, perivascular tumor cells, and general tumor cell expression) was determined by immunofluorescent staining. Expression of NRP1 in perivascular tumor cells was explored as a marker for RCC survival in the two RCC cohorts. Results were further validated using a publicly available gene expression dataset of clear cell RCC (ccRCC). We found that VEGFR2/NRP1 trans complexes were detected in 75% of the patient samples. The presence of trans VEGFR2/NRP1 complexes or perivascular NRP1 expression was associated with a reduced tumor vessel density and size. When exploring NRP1 as a biomarker for RCC prognosis, perivascular NRP1 and general tumor cell NRP1 protein expression correlated with improved survival in the two independent cohorts, and significant results were obtained also at the mRNA level using the publicly available ccRCC gene expression dataset. Only perivascular NRP1 expression remained significant in multivariable analysis. Our work shows that perivascular NRP1 expression is an independent marker of improved survival in RCC patients, and reduces tumor vascularization by forming complexes in trans with VEGFR2 in the tumor endothelium. \u00a9 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.", "doi": "10.1002/path.5380", "pmid": "31880322", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7155095"}], "notes": [], "created": "2026-08-21T11:03:48.988Z", "modified": "2026-08-21T11:03:49.343Z"}]}