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Weins, Astrid

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Weins

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Astrid

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Weins, Astrid

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2015 - 20172

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Author's Publications: search.filters.isAuthorOfPublication.cd3b184f-2446-43d8-bf3f-808a03384c14

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    Nanoscale imaging of clinical specimens using pathology-optimized expansion microscopy
    (2017) Zhao, Yongxin; Bucur, Octavian; Irshad, Humayun; Chen, Fei; Weins, Astrid; Stancu, Andreea; Oh, Eun-Young; DiStasio, Marcello; Torous, Vanda; Glass, Benjamin; Stillman, Isaac; Schnitt, Stuart; Beck, Andrew; Boyden, Edward S.
    Expansion microscopy (ExM), a method for improving the resolution of light microscopy by physically expanding the specimen, has not been applied to clinical tissue samples. Here we report a clinically optimized form of ExM that supports nanoscale imaging of human tissue specimens that have been fixed with formalin, embedded in paraffin, stained with hematoxylin and eosin (H&E), and/or fresh frozen. The method, which we call expansion pathology (ExPath), converts clinical samples into an ExM-compatible state, then applies an ExM protocol with protein anchoring and mechanical homogenization steps optimized for clinical samples. ExPath enables ~70 nm resolution imaging of diverse biomolecules in intact tissues using conventional diffraction-limited microscopes, and standard antibody and fluorescent DNA in situ hybridization reagents. We use ExPath for optical diagnosis of kidney minimal-change disease, which previously required electron microscopy (EM), and demonstrate high-fidelity computational discrimination between early breast neoplastic lesions that to date have challenged human judgment. ExPath may enable the routine use of nanoscale imaging in pathology and clinical research.
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    Control of signaling-mediated clearance of apoptotic cells by the tumor suppressor p53
    (American Association for the Advancement of Science (AAAS), 2015) Yoon, K. W.; Byun, S.; Kwon, Eunjeong; Hwang, So-Young; Chu, Kiki; Hiraki, Masatsugu; Jo, Seung-Hee; Weins, Astrid; Hakroush, Samy; Cebulla, Angelika; Sykes, David; Greka, Anna; Mundel, Peter; Fisher, David; Mandinova, Anna; Lee, Sam
    The inefficient clearance of dying cells can lead to abnormal immune responses, such as unresolved inflammation and autoimmune conditions. We show that tumor suppressor p53 controls signaling-mediated phagocytosis of apoptotic cells through its target, Death Domain1α (DD1α), which suggests that p53 promotes both the proapoptotic pathway and postapoptotic events. DD1α appears to function as an engulfment ligand or receptor that engages in homophilic intermolecular interaction at intercellular junctions of apoptotic cells and macrophages, unlike other typical scavenger receptors that recognize phosphatidylserine on the surface of dead cells. DD1α-deficient mice showed in vivo defects in clearing dying cells, which led to multiple organ damage indicative of immune dysfunction. p53-induced expression of DD1α thus prevents persistence of cell corpses and ensures efficient generation of precise immune responses.