{"id":62,"date":"2015-05-01T09:30:10","date_gmt":"2015-05-01T13:30:10","guid":{"rendered":"http:\/\/wp.cvb.uchc.uconn.edu\/?page_id=62"},"modified":"2026-07-10T12:14:13","modified_gmt":"2026-07-10T16:14:13","slug":"shapiro-lab","status":"publish","type":"page","link":"https:\/\/health.uconn.edu\/vascular-biology\/shapiro-lab\/","title":{"rendered":"Shapiro Lab"},"content":{"rendered":"

Shapiro Lab<\/strong><\/p>\n

NEW PUBLICATION<\/strong><\/p>\n

CD13 activation assembles phosphoinositide (PI) signaling complexes to regulate the actin cytoskeleton<\/a>. Meredith E, Aguilera B, Sharma R, Thimma N, McGurk F, Zong P, Yue L, Shapiro LH, Ghosh M. Sci Rep. 2026 Jan 14;16(1):5191. doi: 10.1038\/s41598-026-35022-6.
\nPMID: 41530254.<\/p>\n

PUBLICATIONS<\/strong><\/p>\n

All Shapiro Lab Publications: https:\/\/www.ncbi.nlm.nih.gov\/myncbi\/linda%20h..shapiro.1\/bibliography\/public\/\u00a0<\/a><\/p>\n

OVERVIEW<\/strong><\/p>\n

Research in the Shapiro Laboratory focuses on understanding the physiological and pathological regulation and function of the M1 family cell-surface peptidase CD13\/aminopeptidase N in inflammation and angiogenesis.<\/p>\n

CD13 in myeloid cell-cell fusion:<\/p>\n

a. Myeloid cell fusion contributes to the formation of osteoclasts and foreign body giant cells (FBGCs) in response to implanted medical devices such as heart valves, intraocular lenses, and sensors. FBGCs trigger immune responses, secreting mediators that cause tissue and device destruction, leading to device failure. Higher levels of FBGCs worsen foreign body response (FBR), and controlling FBGC formation could be a potential solution.
\nb. CD13 knockout (CD13KO) mice exhibit increased numbers of FBGCs and elevated levels of FBR mediators.
\nMechanistically, CD13 deficiency sustains the expression of fusogenic proteins in FBGCs due to defective ubiquitination and stability, therefore, CD13 functions as a brake on uncontrolled cell fusion and may serve as a therapeutic target.
\nc. Human CD13 monoclonal antibodies (mAbs) can either promote or inhibit CD13-dependent fusion, offering therapeutic potential. We created humanized mice expressing human CD13 to test responses to fusion-regulatory mAbs. Coating implants with these mAbs and studying the tissue\/implant interface confirmed the role of FBGCs in FBR.
\nd. Future research will identify optimal mAbs, develop additional candidates, and assess their therapeutic effects in vivo, focusing on FBGC fusion mechanisms and pathways using animal models, primary cells, CRISPR lines, mAbs, inhibitors, and advanced techniques to explore these processes.<\/p>\n

CD13 in inflammation:<\/p>\n

a. CD13 is a homotypic adhesion molecule that mediates adhesion between circulating monocytes and activated endothelium. Crosslinking of CD13 with ligand-mimicking antibodies induces signal transduction events that result in a remarkable increase in adhesion.
\nb. Molecular mechanisms of CD13 adhesion. CD13-dependent adhesion requires its phosphorylation for adhesion, inflammatory monocyte migration, and signal transduction.
\nc. Inflammatory trafficking in ischemic disease. In models of ischemic skeletal muscle injury and cardiac ischemia, the absence of CD13 significantly alters myeloid trafficking in ischemic skeletal and cardiac muscles, resulting in skewed cytokine profiles and implicating CD13 in angiogenesis, inflammatory trafficking, and healing.
\nd. Receptor endocytosis. CD13 regulates endocytosis of numerous receptors, including TLR4, the mannose receptor, TfR, B2R, and S1P1R. The absence of CD13 leads to dysregulated signal transduction cascades, suggesting that CD13 is a functional regulator of innate immunity.<\/p>\n

CD13 and endosomal trafficking:<\/p>\n

a. CD13 regulates focal adhesions. CD13 localizes at focal adhesions (FA) and cell-cell junctions in adherent cells. Phenotypically, CD13KO mouse embryonic fibroblasts (MEFs) show fewer actin stress fibers and microtubule extensions with marked alterations in the localization of the FA proteins Vinculin, Paxillin and Talin, indicating FA formation is defective in the absence of CD13. In keeping with this disrupted cytoskeletal organization in CD13KO cells, \u03b21-integrin failed to cluster in response to ligand-coated beads and phosphorylation of FAK and Src was reduced, consistent with a link between CD13 and the control of FA dynamics.
\nb. In WT MEFs, CD13 and \u03b21-integrin co-internalize, traffic to EEA1+ and Rab5+ early endosomes and recycle to the plasma membrane together via Rab11a+ recycling endosomes. Conversely in CD13KO MEFs, internalized \u03b21-integrin is again found in early endosomes but rather than recycling, integrin traffics from early endosomes to Rab7+ late endosomes\/lysosomes. Pulse-chase assays confirmed that CD13 is necessary for \u03b21-integrin recycling to the cell surface and that this process requires CD13 phosphorylation.
\nc. CD13 regulates angiogenesis: We demonstrated that induction of CD13 expression on angiogenic vasculature regulates endothelial invasion to regulate angiogenesis.<\/p>\n

    \n
  1. CD13 is a receptor for tumor-homing peptides and a target for inhibiting angiogenesis. NGR peptide motif homes to CD13 on tumor vasculature in vivo. CD13 antagonists specifically inhibit angiogenesis and suppress tumor growth. Thus, CD13 is involved in angiogenesis and can serve as a target for delivering drugs into tumors and for inhibiting angiogenesis.<\/li>\n
  2. CD13 endothelial transcription is induced by angiogenic growth factors and the Ras\/MAPK pathway. We showed that endogenous CD13 levels are up-regulated in response to hypoxia, angiogenic growth factors, and signals regulating capillary tube formation during angiogenesis due to Ras signal transduction.<\/li>\n
  3. CD13 is a functional regulator of angiogenesis. Functional antagonists of CD13\/APN interfere with tube formation but not proliferation of primary vascular endothelial cells, suggesting that CD13\/APN functions in the control of endothelial cell invasion.<\/li>\n<\/ol>\n

    Therefore, we have assembled the tools and necessary critical observations and have made significant progress toward elucidating the mechanisms governing the various impacts of CD13 on many cellular processes, the identification of its regulatory pathways and activating ligands, and their roles in vascular physiology, cardiovascular disease, and now bones and implants.<\/p>\n","protected":false},"excerpt":{"rendered":"

    Shapiro Lab NEW PUBLICATION CD13 activation assembles phosphoinositide (PI) signaling complexes to regulate the actin cytoskeleton. Meredith E, Aguilera B, Sharma R, Thimma N, McGurk F, Zong P, Yue L, Shapiro LH, Ghosh M. Sci Rep. 2026 Jan 14;16(1):5191. doi: 10.1038\/s41598-026-35022-6. PMID: 41530254. PUBLICATIONS All Shapiro Lab Publications: https:\/\/www.ncbi.nlm.nih.gov\/myncbi\/linda%20h..shapiro.1\/bibliography\/public\/\u00a0 OVERVIEW Research in the Shapiro Laboratory […]<\/p>\n","protected":false},"author":38,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"acf":[],"publishpress_future_action":{"enabled":false,"date":"2026-07-23 12:48:29","action":"change-status","newStatus":"draft","terms":[],"taxonomy":""},"_links":{"self":[{"href":"https:\/\/health.uconn.edu\/vascular-biology\/wp-json\/wp\/v2\/pages\/62"}],"collection":[{"href":"https:\/\/health.uconn.edu\/vascular-biology\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/health.uconn.edu\/vascular-biology\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/health.uconn.edu\/vascular-biology\/wp-json\/wp\/v2\/users\/38"}],"replies":[{"embeddable":true,"href":"https:\/\/health.uconn.edu\/vascular-biology\/wp-json\/wp\/v2\/comments?post=62"}],"version-history":[{"count":13,"href":"https:\/\/health.uconn.edu\/vascular-biology\/wp-json\/wp\/v2\/pages\/62\/revisions"}],"predecessor-version":[{"id":979,"href":"https:\/\/health.uconn.edu\/vascular-biology\/wp-json\/wp\/v2\/pages\/62\/revisions\/979"}],"wp:attachment":[{"href":"https:\/\/health.uconn.edu\/vascular-biology\/wp-json\/wp\/v2\/media?parent=62"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}