{"id":6255,"date":"2026-10-19T09:48:41","date_gmt":"2026-10-19T09:48:41","guid":{"rendered":"https:\/\/phd.hi.is\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-sigurdur-trausti-karvelsson\/"},"modified":"2026-10-19T09:48:41","modified_gmt":"2026-10-19T09:48:41","slug":"doktorsvorn-i-lif-og-laeknavisindum-sigurdur-trausti-karvelsson","status":"publish","type":"phd_defence","link":"https:\/\/phd.hi.is\/en\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-sigurdur-trausti-karvelsson\/","title":{"rendered":"Doktorsv\u00f6rn \u00ed l\u00edf- og l\u00e6knav\u00edsindum – Sigur\u00f0ur Trausti Karvelsson"},"content":{"rendered":"
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F\u00f6studaginn 25. febr\u00faar ver Sigur\u00f0ur Trausti Karvelsson doktorsritger\u00f0 s\u00edna \u00ed l\u00edf- og l\u00e6knav\u00edsindum vi\u00f0 L\u00e6knadeild H\u00e1sk\u00f3la \u00cdslands. Ritger\u00f0in ber heiti\u00f0: Kerfisl\u00edffr\u00e6\u00f0ileg efnaskiptagreining \u00e1 brj\u00f3sta\u00feekjufrumum vi\u00f0 bandvefsumbreytingu. Metabolic systems analysis of breast epithelial cells following epithelial-to-mesenchymal transition.<\/p>\n

Andm\u00e6lendur eru dr. Vignir Helgason, d\u00f3sent vi\u00f0 University of Glasgow, og dr. Jason Locasale, pr\u00f3fessor vi\u00f0 Duke University School of Medicine.<\/p>\n

Umsj\u00f3narkennari og lei\u00f0beinandi var \u00d3ttar Rolfsson, pr\u00f3fessor, og me\u00f0lei\u00f0beinandi var Steinn Gu\u00f0mundsson, pr\u00f3fessor. Auk \u00feeirra s\u00e1tu \u00ed doktorsnefnd Margr\u00e9t \u00deorsteinsd\u00f3ttir, pr\u00f3fessor, Skarph\u00e9\u00f0inn Halld\u00f3rsson og \u00de\u00f3runn Rafnar, yfirma\u00f0ur krabbameinsranns\u00f3kna \u00cdE.<\/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. 09.00. V\u00f6rninni ver\u00f0ur streymt:\u00a0<\/p>\n

https:\/\/livestream.com\/hi\/doktorsvornsigurdurtraustikarvelsson<\/a><\/p>\n

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

Brj\u00f3stakrabbamein er marg\u00fe\u00e6ttur sj\u00fakd\u00f3mur \u00fear sem bo\u00f0skiptaferli, genatj\u00e1ning, efnaskiptaferli og vaxtarferli \u00ed brj\u00f3stavef eru g\u00f6llu\u00f0. Sj\u00fakd\u00f3murinn veldur dau\u00f0a yfir 600.000 manns \u00ed heiminum \u00e1 \u00e1ri hverju. Me\u00f0 \u00fev\u00ed a\u00f0 rannsaka l\u00edffr\u00e6\u00f0ileg ferli \u00ed e\u00f0lilegum brj\u00f3stavef f\u00e6st betri inns\u00fdn \u00ed meinafr\u00e6\u00f0i brj\u00f3stakrabbameins. \u00cd \u00feessari ritger\u00f0 var einbl\u00ednt \u00e1 \u00feroskunarfr\u00e6\u00f0ilegt ferli sem nefnist bandvefsumbreyting sem talin er nau\u00f0synleg fyrir myndun meinvarpa. S\u00e9rstaklega var einbl\u00ednt \u00e1 efnaskiptabreytingar samhli\u00f0a \u00feessu ferli \u00ed brj\u00f3sta\u00feekjufrumum.<\/p>\n

Ritger\u00f0in skiptist \u00ed \u00ferj\u00e1 hluta. \u00cd fyrsta hlutanum var 13C sams\u00e6tugreining notu\u00f0 til a\u00f0 skilgreina efnaskiptabreytingar sem gerast samhli\u00f0a bandvefsumbreytingu D492 brj\u00f3sta\u00feekjufrumul\u00ednunnar. Ni\u00f0urst\u00f6\u00f0ur s\u00fdndu a\u00f0 frumul\u00ednan minnka\u00f0i sykurrofsvirkni og j\u00f3k afoxandi karbox\u00fdleringu am\u00edn\u00f3s\u00fdrunnar gl\u00fatam\u00edns. Aukinheldur breyttust efnaskipti oxun\/afoxunarhvarfa, \u00fear sem me\u00f0al annars myndun gl\u00fata\u00fe\u00ed\u00f3ns minnka\u00f0i umtalsvert, sem haf\u00f0i bein \u00e1hrif \u00e1 lyfjan\u00e6mi frumnanna.<\/p>\n

\u00cd \u00f6\u00f0rum hluta ritger\u00f0arinnar var notkunargildi efnaskiptal\u00edkana til a\u00f0 sp\u00e1 fyrir um efnaskipti D492 frumul\u00ednunnar fyrir og eftir bandvefsumbreytingu sko\u00f0u\u00f0. Mismunandi mengjag\u00f6gn voru notu\u00f0 til a\u00f0 skor\u00f0a l\u00edk\u00f6nin. L\u00edk\u00f6n skor\u00f0u\u00f0 me\u00f0 pr\u00f3teinmengjag\u00f6gnum reyndust n\u00e1kv\u00e6must \u00ed sp\u00e1m \u00e1 fl\u00e6\u00f0igildum efnahvarfa, samanbori\u00f0 vi\u00f0 ni\u00f0urst\u00f6\u00f0ur \u00far 13C sams\u00e6tugreiningum. Frekari greining \u00e1 l\u00edk\u00f6num skor\u00f0u\u00f0um me\u00f0\u00a0 pr\u00f3teinmengjag\u00f6gnum s\u00fdndi fram \u00e1 n\u00fdtanlega veiklun \u00ed efnaskiptum frumnanna sem sta\u00f0fest voru me\u00f0 frumul\u00edffr\u00e6\u00f0itilraunum. A\u00f0 lokum voru pr\u00f3teinmengjag\u00f6gn \u00far brj\u00f3stakrabbameins\u00e6xlum \u00far sj\u00faklingum notu\u00f0 til a\u00f0 skor\u00f0a efnaskiptal\u00edkani\u00f0, sem s\u00fdndi fram \u00e1 m\u00f6gulega l\u00edfv\u00edsa fyrir lifun brj\u00f3stakrabbameinssj\u00faklinga \u00ed mismunandi undirflokkum.\u00a0<\/p>\n

\u00cd \u00feri\u00f0ja og s\u00ed\u00f0asta hluta ritger\u00f0arinnar var hlutverk GFPT2 ens\u00edmsins \u00ed bandvefsumbreytingu og \u00e6xlismyndun \u00ed brj\u00f3stavef rannsaka\u00f0. Greining \u00e1 pr\u00f3teinmengi D492 frumul\u00ednunnar (i) fyrir bandvefsumbreytingu, (ii) eftir bandvefsumbreytingu og (iii) eftir oftj\u00e1ningu \u00e6xlisgensins HER2 leiddi \u00ed lj\u00f3s j\u00e1kv\u00e6tt samband milli pr\u00f3teinmagns GFPT2 ens\u00edmsins og bandvefsumbreytingarst\u00f6\u00f0u frumul\u00ednanna. Frekari sameindal\u00edffr\u00e6\u00f0ilegar og l\u00edfuppl\u00fdsingafr\u00e6\u00f0ilegar ranns\u00f3knir bentu \u00e1 a\u00f0 GFPT2 v\u00e6ri mikilv\u00e6gt fyrir fj\u00f6lsykruefnaskipti og sv\u00f6run frumnanna vi\u00f0 oxunar\u00e1lagi vi\u00f0 bandvefsumbreytingu og \u00e6xlismyndun.<\/p>\n

Ni\u00f0urst\u00f6\u00f0ur verkefnisins hafa auki\u00f0 skilning okkar \u00e1 \u00feeim efnaskiptabreytingum sem eiga s\u00e9r sta\u00f0 vi\u00f0 bandvefsumbreytingu brj\u00f3sta\u00feekjufrumna og hvernig \u00fe\u00e6r hafa \u00e1hrif \u00e1 lyfjan\u00e6mi \u00feeirra. Einnig er h\u00e9r s\u00fdnt fram \u00e1 hve gagns\u00f6m efnaskiptal\u00edk\u00f6n skor\u00f0u\u00f0 af mengjag\u00f6gnum geta veri\u00f0 \u00feegar kemur a\u00f0 \u00fev\u00ed a\u00f0 rannsaka efnaskipti b\u00e6\u00f0i e\u00f0lilegs brj\u00f3sta\u00feekjuvefs og brj\u00f3stakrabbameins.<\/p>\n

English abstract<\/strong><\/p>\n

Breast cancer is a heterogenous disease in which the mechanism for signalling, gene expression, metabolism and growth in breast tissue is deranged. Breast cancer is responsible for the death of over 600,000 people worldwide on a yearly basis. By investigating cellular processes in normal breast tissue, one may gain further insight into the pathophysiology of breast cancer. In this thesis, the main focal point was a developmental process called epithelial-to-mesenchymal transition (EMT), which has been shown to be fundamental for cancer dissemination. More specifically, the metabolic alterations following this process in breast epithelial cells were investigated. This thesis is in three parts. In the first part,13C isotope tracer analysis was used to characterize the metabolic differences that occur following EMT of the breast epithelial cell line D492. The results showed that following EMT, the breast cell line reduced its glycolytic activity and enhanced the reductive carboxylation of glutamine. Furthermore, the redox metabolism was affected, with glutathione synthesis being decreased significantly, which was found to affect the drug sensitivity of the cells. In the second part of the thesis, the capability of genome-scale metabolic models (GSMMs) to predict the metabolic alterations following EMT of the D492 cell line was investigated. Different types of omics data were used to constrain the GSMM, where the results showed that the models constrained with proteomic data were the most accurate in metabolic flux predictions when compared to results from a 13C isotope tracer analysis. The proteomic GSMMs were analysed in more detail to identify metabolic vulnerabilites of the cells, which were confirmed in vitro. Finally, proteomic data from breast cancer patients werre used to constrain the GSMM, which helped to identify subtype-specific prognostic markers of breast cancer patient survival. In the third and final part of the thesis, the role of the enzyme GFPT2 in EMT and breast tumourigenesis was investigated. A proteomic analysis of the D492 cell line (i) before EMT, (ii) after EMT and (iii) after overexpression of the HER2 oncogene revealed that protein levels of GFPT2 were highly correlated with the EMT status of the cell lines. Further molecular biology experiments and bioinformatic analyses revealed that GFPT2 was important for glycan metabolism and the oxidative stress response of the cells during EMT and tumourigenesis.<\/p>\n

In summary, the results presented in this thesis increase our knowledge about the metabolic reprogramming that occurs following EMT in breast cells, and how it relates in part to the altered drug sensitivity of the cells. It was also demonstrated how useful omics data-constrained GSMMs may be in studying the metabolism of both normal and tumourigenic breast tissue.<\/p>\n

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

Sigur\u00f0ur Trausti Karvelsson er f\u00e6ddur \u00e1ri\u00f0 1992 \u00e1 Akranesi. \u00a0Hann lauk st\u00fadentspr\u00f3fi af n\u00e1tt\u00farufr\u00e6\u00f0ibraut fr\u00e1 Fj\u00f6lbrautask\u00f3la Vesturlands \u00e1 Akranesi \u00e1ri\u00f0 2011, BS-pr\u00f3fi \u00ed l\u00edfefna- og sameindal\u00edffr\u00e6\u00f0i fr\u00e1 H\u00e1sk\u00f3la \u00cdslands \u00e1ri\u00f0 2015 og meistarapr\u00f3fi \u00ed l\u00edf- og l\u00e6knav\u00edsindum fr\u00e1 H\u00e1sk\u00f3la \u00cdslands \u00e1ri\u00f0 2017. Samhli\u00f0a doktorsn\u00e1minu sinnti Sigur\u00f0ur kennslu \u00ed l\u00edfefnafr\u00e6\u00f0i og kerfisl\u00edffr\u00e6\u00f0i vi\u00f0 H\u00e1sk\u00f3la \u00cdslands, en hann starfar n\u00fa sem v\u00edsindama\u00f0ur hj\u00e1 lyfjafyrirt\u00e6kinu Alvotech \u00ed Reykjav\u00edk. Foreldrar Sigur\u00f0ar eru Hrefna Sigur\u00f0ard\u00f3ttir og Karvel Lindberg Karvelsson. Maki Sigur\u00f0ar er Margr\u00e9t Helga Isaksen, hj\u00fakrunarfr\u00e6\u00f0inemi, og eiga \u00feau b\u00f6rnin \u00c1sthildi Leu og Harald \u00d3la.<\/p>\n<\/div><\/div>","protected":false},"featured_media":5074,"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":"2022-02-25T09:00:00+00:00","_phd_date_end":"2022-02-25T12:00:00+00:00","_phd_location":"A\u00f0albygging H\u00e1t\u00ed\u00f0asalur","_phd_admission":"A\u00f0gangur \u00f3keypis","_phd_thesis_title":"Kerfisl\u00edffr\u00e6\u00f0ileg efnaskiptagreining \u00e1 brj\u00f3sta\u00feekjufrumum vi\u00f0 bandvefsumbreytingu. 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