{"id":34,"date":"2017-05-09T16:27:23","date_gmt":"2017-05-09T16:27:23","guid":{"rendered":"http:\/\/vaccarilab.unimi.it\/?page_id=34"},"modified":"2021-02-07T17:34:14","modified_gmt":"2021-02-07T17:34:14","slug":"research","status":"publish","type":"page","link":"https:\/\/www.vaccarilab.unimi.it\/index.php\/research\/","title":{"rendered":"Research"},"content":{"rendered":"

The lab has currently 4 established lines of research:<\/p>\n

1- New mechanisms of autophagy relevant to neurodegeneration
\n<\/strong><\/p>\n

\"\"We explore the molecular requirements of autophagy and detail the function of novel factors in the process. For instance, we discovered Snap29, a new SNARE protein that specifically controls completion of autophagy (read about it<\/a>). We have also found that\u00a0 Snap29 is likely controls kinetochore formation, ensuring appropriate spindle formation and execution of cell division (read about it<\/a>). We are now investigating the role of Snap29 and other molecules associated to autophagy and proteostasis in neurodegeneration (read about it<\/a>).<\/p>\n

In the figure<\/span>: Models of Snap29 activity in membrane fusion and kinetochore formation.<\/p>\n

2- Regulation of Notch signaling<\/strong><\/p>\n

We untangled long-standing controversies concerning the regulation of Notch signaling by endocytosis, showing that in fly tissue the activating S3 cleavage of Notch occurs in acidic endosomal compartments and that the V-ATPase is a determinant of Notch activation (read about it<\/a>). We also showed that V-ATPase is regulated to support Notch signaling during fly development, and that such process involves \u00a0regulation of lysosome biogenesis and autophagy (read about it<\/a>). We continue to identify and characterize new regulators of Notch signaling. The results collectively might inform therapeutic approaches to Notch- and V-ATPase-dependent tumors.<\/p>\n

\"\"<\/p>\n

In the figure<\/span>: Egg chambers of the Drosophila ovary stained to detect Notch (red) and expressing V-ATPase subunit c tagged with GFP (green). The cell nuclei are labeled in blue. Note the colocalization of Notch with V-ATPase in endosomes (yellow)\u00a0in the follicular epithelium covering the germline.<\/p>\n

3- Endo-lysosomal function, tissue development and tumorigenesis<\/strong><\/p>\n

We resuscitated the study of Drosophila tumor suppressor genes with the demonstration that ESCRT-mediated endosomal sorting is necessary to prevent tumorigenesis (read about it<\/a>). We explored the functional differences between ESCRT complexes and showed that ESCRT-0 is involved in endosomal sorting but not in tumor suppression, highlighting a major difference in their activity (read about it<\/a>). We continue to study aspects of this in fly models of brain tumors.<\/p>\n

\"\"<\/p>\n

In the figure<\/span>: Wild type Drosophila larvae (left) and chimeric larvae (right) carrying a ESCRT-mutant tumorous eye-antennal imaginal disc (right inset). Note the loss of epithelial morphology and overproliferation compared to the monolayer epithelium of a control eye-antennal disc (left inset).<\/p>\n

4- Fly models of rare disease<\/strong><\/p>\n

We continue to use Drosophila<\/em> and other simple models as avatars of patients affected by rare disease that cannot count on a lot of support for research. We have extensively investigated the pathogenesis of CEDNIK disease caused by loss of SNAP29 (read about it<\/a>), we studied models of Cornelia De Lange syndrome (read about it<\/a>), and we are providing insight relevant to congenital disorders of glycosylation (read about it<\/a>) and lysosomal storage disorders. Stay tuned!<\/p>\n","protected":false},"excerpt":{"rendered":"

The lab has currently 4 established lines of research: 1- New mechanisms of autophagy relevant to neurodegeneration We explore the molecular requirements of autophagy and detail the function of novel factors in the process. For instance, we discovered Snap29, a … Continued<\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"page-fullwidth.php","meta":{"kt_blocks_editor_width":"","footnotes":""},"class_list":["post-34","page","type-page","status-publish","hentry"],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/www.vaccarilab.unimi.it\/index.php\/wp-json\/wp\/v2\/pages\/34","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.vaccarilab.unimi.it\/index.php\/wp-json\/wp\/v2\/pages"}],"about":[{"href":"https:\/\/www.vaccarilab.unimi.it\/index.php\/wp-json\/wp\/v2\/types\/page"}],"author":[{"embeddable":true,"href":"https:\/\/www.vaccarilab.unimi.it\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.vaccarilab.unimi.it\/index.php\/wp-json\/wp\/v2\/comments?post=34"}],"version-history":[{"count":25,"href":"https:\/\/www.vaccarilab.unimi.it\/index.php\/wp-json\/wp\/v2\/pages\/34\/revisions"}],"predecessor-version":[{"id":591,"href":"https:\/\/www.vaccarilab.unimi.it\/index.php\/wp-json\/wp\/v2\/pages\/34\/revisions\/591"}],"wp:attachment":[{"href":"https:\/\/www.vaccarilab.unimi.it\/index.php\/wp-json\/wp\/v2\/media?parent=34"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}