{"id":6402,"date":"2026-10-19T09:48:52","date_gmt":"2026-10-19T09:48:52","guid":{"rendered":"https:\/\/phd.hi.is\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-clemence-larat\/"},"modified":"2026-10-19T09:48:52","modified_gmt":"2026-10-19T09:48:52","slug":"doktorsvorn-i-lif-og-laeknavisindum-clemence-larat","status":"publish","type":"phd_defence","link":"https:\/\/phd.hi.is\/en\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-clemence-larat\/","title":{"rendered":"Doktorsv\u00f6rn \u00ed l\u00edf- og l\u00e6knav\u00edsindum – Cl\u00e9mence Larat"},"content":{"rendered":"
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M\u00e1nudaginn 2. j\u00fan\u00ed 2025 ver Cl\u00e9mence Larat doktorsritger\u00f0 s\u00edna \u00ed l\u00edf- og l\u00e6knav\u00edsindum vi\u00f0 L\u00e6knadeild H\u00e1sk\u00f3la \u00cdslands. Ritger\u00f0in ber heiti\u00f0: Hlu<\/strong>tverk ATG7 is\u00f3forma \u00ed krabbameinum. An isoform specific role of the autophagy protein ATG7 in cancer.<\/strong><\/p>\n

Andm\u00e6lendur eru dr. Thomas McWilliams, d\u00f3sent vi\u00f0 H\u00e1sk\u00f3lann \u00ed Helsinki, og dr. Sigurd\u00eds Haraldsd\u00f3ttir, d\u00f3sent vi\u00f0 L\u00e6knadeild.<\/p>\n

Umsj\u00f3narkennari og lei\u00f0beinandi var Margr\u00e9t Helga \u00d6gmundsd\u00f3ttir, pr\u00f3fessor. Auk hennar s\u00e1tu \u00ed doktorsnefnd Bylgja Hilmarsd\u00f3ttir, lektor, Siggeir Fannar Brynj\u00f3lfsson, d\u00f3sent, og Vignir Helgason, pr\u00f3fessor.<\/p>\n

\u00de\u00f3rarinn Gu\u00f0j\u00f3nsson, pr\u00f3fessor og deildarforseti L\u00e6knadeildar, stj\u00f3rnar ath\u00f6fninni sem fer fram \u00ed H\u00e1t\u00ed\u00f0asal H\u00e1sk\u00f3la \u00cdslands og hefst kl. 13.00.<\/p>\n

\u00c1grip<\/strong><\/p>\n

Sj\u00e1lfs\u00e1t er ni\u00f0urbrotsferli frumna og er mikilv\u00e6gt til a\u00f0 vi\u00f0halda frumujafnv\u00e6gi. S\u00fdnt hefur veri\u00f0 fram \u00e1 a\u00f0 \u00fea\u00f0 tekur \u00fe\u00e1tt \u00ed myndun og \u00fer\u00f3un krabbameins, anna\u00f0hvort \u00e1 \u00e6xlisb\u00e6landi e\u00f0a -\u00f6rvandi h\u00e1tt. ATG7 er nau\u00f0synlegt fyrir upphaf sj\u00e1lfs\u00e1ts me\u00f0 \u00fev\u00ed a\u00f0 tengja ATG8 pr\u00f3tein vi\u00f0 l\u00edp\u00ed\u00f0. Greint hefur veri\u00f0 stutt \u00eds\u00f3form, kalla\u00f0 ATG7(2), sem skortir 27 am\u00edn\u00f3s\u00fdrur \u00ed hinu virka sv\u00e6\u00f0i pr\u00f3teinsins samanbori\u00f0 vi\u00f0 fullu lengd pr\u00f3teinsins, ATG7(1). ATG7(2) getur ekki bundi\u00f0 ATG8 pr\u00f3tein vi\u00f0 himnur og skortir \u00fev\u00ed skilgreinda virkni ATG7. Vita\u00f0 er a\u00f0 ATG7 gegnir hlutverki \u00ed framvindu krabbameins og meinv\u00f6rpum og \u00fea\u00f0 hlutverk hefur lengi veri\u00f0 tengt sj\u00e1lfs\u00e1ti. Hins vegar benda n\u00fdlegar ranns\u00f3knir til \u00feess a\u00f0 \u00feetta hlutverk g\u00e6ti a\u00f0 hluta til veri\u00f0 \u00f3h\u00e1\u00f0 sj\u00e1lfs\u00e1ti.<\/p>\n

Til a\u00f0 skilja hlutverk ATG7(2) voru greind kl\u00edn\u00edsk g\u00f6gn \u00far opnum gagnagrunnum. \u00deetta s\u00fdndi a\u00f0 h\u00e1 ATG7(2) tj\u00e1ning tengist sl\u00e6mum horfum \u00ed briskrabbameini (PAAD). S\u00ed\u00f0an var m\u00e6ld mRNA tj\u00e1ning ATG7(1) og ATG7(2) \u00ed heilbrig\u00f0um s\u00fdnum bori\u00f0 saman vi\u00f0 briskrabbamein og s\u00e1st aukning \u00ed tj\u00e1ningu beggja \u00eds\u00f3forma \u00ed \u00e6xliss\u00fdnunum. \u00deegar \u00feetta var greint \u00e1 kl\u00edn\u00edskum stigum PAAD s\u00e1st aukin tj\u00e1ning ATG7(2) \u00e1 stigi IV samanbori\u00f0 vi\u00f0 \u00f6nnur stig. A\u00f0 lokum leiddi greining \u00ed lj\u00f3s a\u00f0 \u00f3n\u00e6misvirk \u00e6xli tj\u00e1 h\u00e6rra magn af ATG7(2) en \u00f3n\u00e6mis\u00f3virk \u00e6xli, \u00ed \u00f6llum krabbameinum.<\/p>\n

Me\u00f0 \u00fev\u00ed a\u00f0 nota CRISPR\/Cas9 \u00ed PAAD frumul\u00ednu var slegi\u00f0 \u00fat megin\u00eds\u00f3formi\u00f0 ATG7(1) e\u00f0a heildar ATG7. Ger\u00f0 voru fj\u00f6lgunar- og frumuskri\u00f0spr\u00f3f \u00e1 kl\u00f3num sem tj\u00e1\u00f0u mismunandi magn af ATG7(2). \u00de\u00f3 a\u00f0 heildar\u00fatsl\u00e1ttur ATG7 hafi veri\u00f0 tengdur h\u00e6gu frumuskri\u00f0i s\u00fdndi ATG7(1)-\/- hra\u00f0ari frumufj\u00f6lgun og skri\u00f0, s\u00e9rstaklega me\u00f0 h\u00e1u magni ATG7(2). Saman benda \u00feessar ni\u00f0urst\u00f6\u00f0ur til \u00feess a\u00f0 ATG7(2) g\u00e6ti kn\u00fai\u00f0 \u00e1fram skri\u00f0 og fj\u00f6lgun \u00ed PAAD frumum \u00e1 sj\u00e1lfs\u00e1ts\u00f3h\u00e1\u00f0an h\u00e1tt.<\/p>\n

A\u00f0 lokum var nota\u00f0 siRNA til a\u00f0 sl\u00e1 s\u00e9rstaklega ni\u00f0ur ATG7(2) \u00ed samanbur\u00f0ar- og ATG7(1)-\/- frumum. \u00deetta leiddi til minni skri\u00f0- og fj\u00f6lgunarhra\u00f0a \u00ed b\u00e1\u00f0um frumuger\u00f0um mi\u00f0a\u00f0 vi\u00f0 samanbur\u00f0ar-siRNA. \u00deetta verkefni varpar lj\u00f3si \u00e1\u00a0 mikilv\u00e6gi ATG7(2) \u00ed briskrabbameini, sem og hugsanlega n\u00fdja me\u00f0fer\u00f0arm\u00f6guleika.<\/p>\n

Abstract<\/strong><\/p>\n

Autophagy is a cellular degradation process, important for maintaining cellular homeostasis. It has been shown to be involved in cancer initiation and development, either in a tumour-suppressive or promotive manner. The protein ATG7 is known to be essential for autophagy initiation by catalysing the lipidation of ATG8 proteins. Previously, we identified a short isoform, termed ATG7(2), which lacks 27 amino acids in the active domain of the protein, compared with the full-length ATG7(1), and is unable to lipidate ATG8 proteins. ATG7 is known to play a role in cancer progression and metastasis, and this role has long been associated with autophagy. However, recent studies suggest that this role could be, in part, autophagy-independent.<\/p>\n

To understand the role of ATG7(2), we analysed clinical data from publicly available databases. This showed that high ATG7(2) expression is linked with poor prognosis in pancreatic adenocarcinoma (PAAD). Then, we quantified the mRNA expression of ATG7(1) and ATG7(2) in healthy versus cancerous pancreatic samples and observed an increase in the expression of both isoforms in the tumour samples. When analysing this in PAAD clinical stages, we observed increased ATG7(2) expression in Stage IV compared with other stages. Finally, our analysis revealed that immuno-active tumours express higher levels of ATG7(2) than immunologically quiet ones, across cancers.<\/p>\n

Using CRISPR\/Cas9 in a PAAD cell line, we selectively knocked out the canonical isoform ATG7(1) or total ATG7. We performed proliferation and migration assays on clones expressing different levels of endogenous ATG7(2). While total knock-out of ATG7 was linked with slow migration, ATG7(1)-\/- showed faster proliferation and migration, especially with high levels of ATG7(2). Together, these results suggest that ATG7(2) could drive migration and proliferation in PAAD cells in an autophagy-independent manner.<\/p>\n

Finally, we used siRNA to specifically knock down ATG7(2) in control and ATG7(1)-\/- cells. This led to decreased migration and proliferation rates in both cell types compared with control siRNA. This project highlights the importance of ATG7(2) in cancer, and opens new avenues for therapeutic strategies.<\/p>\n

Um doktorsefni\u00f0<\/strong><\/p>\n

Cl\u00e9mence Larat er f\u00e6dd \u00e1ri\u00f0 1997 \u00ed Gap \u00ed Frakklandi. H\u00fan lauk MS-gr\u00e1\u00f0u \u00ed krabbameinsfr\u00e6\u00f0um og MS-gr\u00e1\u00f0u \u00ed l\u00edfverkfr\u00e6\u00f0i fr\u00e1 H\u00e1sk\u00f3lanum \u00ed Marseille \u00e1ri\u00f0 2019. Cl\u00e9mence starfa\u00f0i vi\u00f0 Novartis \u00ed Sviss \u00ed eitt \u00e1r \u00e1\u00f0ur en h\u00fan h\u00f3f doktorsn\u00e1m vi\u00f0 L\u00e6knadeild H\u00e1sk\u00f3la \u00cdslands vori\u00f0 2022.<\/p>\n<\/div><\/div>","protected":false},"featured_media":5766,"template":"","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"_phd_date_start":"2025-06-02T13:00:00+00:00","_phd_date_end":"2025-06-02T16:00:00+00:00","_phd_location":"A\u00f0albygging H\u00e1t\u00ed\u00f0asalur","_phd_admission":"A\u00f0gangur \u00f3keypis","_phd_thesis_title":"Hlutverk ATG7 is\u00f3forma \u00ed krabbameinum. An isoform specific role of the autophagy protein ATG7 in cancer","_phd_source_url":"https:\/\/gamli.hi.is\/vidburdir\/doktorsvorn_i_lif_og_laeknavisindum_clemence_larat","_phd_source_node_id":"441441","_phd_source_type":"vidburdir","_phd_member_id":940,"footnotes":""},"phd_school":[60,67],"phd_discipline":[70],"class_list":["post-6402","phd_defence","type-phd_defence","status-publish","has-post-thumbnail","hentry","phd_school-heilbrigdisvisindasvid","phd_school-laeknadeild","phd_discipline-phd-i-lif-og-laeknavisindum"],"_links":{"self":[{"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/phd_defence\/6402","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/phd_defence"}],"about":[{"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/types\/phd_defence"}],"version-history":[{"count":0,"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/phd_defence\/6402\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/media\/5766"}],"wp:attachment":[{"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/media?parent=6402"}],"wp:term":[{"taxonomy":"phd_school","embeddable":true,"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/phd_school?post=6402"},{"taxonomy":"phd_discipline","embeddable":true,"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/phd_discipline?post=6402"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}