{"id":6375,"date":"2026-10-19T09:48:50","date_gmt":"2026-10-19T09:48:50","guid":{"rendered":"https:\/\/phd.hi.is\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-drifa-hrund-gudmundsdottir\/"},"modified":"2026-10-19T09:48:50","modified_gmt":"2026-10-19T09:48:50","slug":"doktorsvorn-i-lif-og-laeknavisindum-drifa-hrund-gudmundsdottir","status":"publish","type":"phd_defence","link":"https:\/\/phd.hi.is\/en\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-drifa-hrund-gudmundsdottir\/","title":{"rendered":"Doktorsv\u00f6rn \u00ed l\u00edf- og l\u00e6knav\u00edsindum – Dr\u00edfa Hrund Gu\u00f0mundsd\u00f3ttir"},"content":{"rendered":"
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\u00deri\u00f0judaginn 19. n\u00f3vember 2024 ver Dr\u00edfa Hrund Gu\u00f0mundsd\u00f3ttir doktorsritger\u00f0 s\u00edna \u00ed l\u00edf- og l\u00e6knav\u00edsindum vi\u00f0 L\u00e6knadeild H\u00e1sk\u00f3la \u00cdslands. Ritger\u00f0in ber heiti\u00f0: Litfrumu \u00f3s\u00e9rt\u00e6kt hlutverk MITF \u00ed va\u00f0haldi \u00e1 st\u00f6\u00f0ugleika erf\u00f0aefnisins. The non-melanocyte specific role of MITF in the maintenance of genome integrity.<\/strong><\/p>\n

Andm\u00e6lendur eru dr. Kumar Somyajit, d\u00f3sent vi\u00f0 Syddansk Universitet \u00ed Danm\u00f6rku, og dr. Robert Ballotti, ranns\u00f3knastj\u00f3ri og forst\u00f6\u00f0uma\u00f0ur ranns\u00f3knastofu vi\u00f0 C\u00f4te d’Azur University \u00ed Frakklandi.<\/p>\n

Umsj\u00f3narkennari var Stef\u00e1n \u00de. Sigur\u00f0sson, pr\u00f3fessor, og lei\u00f0beinandi var \u00deorkell Gu\u00f0j\u00f3nsson, lektor. Auk \u00feeirra s\u00e1tu \u00ed doktorsnefnd Eir\u00edkur Steingr\u00edmsson, pr\u00f3fessor og claus Storgaard S\u00f6rensen.<\/p>\n

S\u00e6d\u00eds S\u00e6varsd\u00f3ttir, pr\u00f3fessor og varadeildarforseti L\u00e6knadeildar, stj\u00f3rnar ath\u00f6fninni sem fer fram \u00ed H\u00e1t\u00ed\u00f0asal H\u00e1sk\u00f3la \u00cdslands og hefst kl. 09.00.<\/p>\n

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

\u00d3st\u00f6\u00f0ugleiki \u00ed erf\u00f0amenginu vegna DNA-skemmda er eitt helsta einkenni flestra krabbameina. Tv\u00ed\u00fe\u00e1tta DNA-brot eru s\u00e9rstaklega sl\u00e6m \u00fear sem \u00feau auka l\u00edkurnar \u00e1 a\u00f0 erf\u00f0aefni tapist \u00feegar b\u00e1\u00f0ir \u00fer\u00e6\u00f0ir DNA-sameindarinnar brotna. DNA eftirmyndunar\u00e1lag er einnig mikilv\u00e6g uppspretta \u00f3st\u00f6\u00f0ugleika \u00ed erf\u00f0aefninu. Ef DNA-eftirmyndunar\u00e1lag er \u00f3leyst getur \u00fea\u00f0 valdi\u00f0 tv\u00ed\u00fe\u00e1tta DNA-brotum og litningaskemmdum sem geta haft veruleg \u00e1hrif \u00e1 e\u00f0lilega frumustarfsemi. \u00deegar erf\u00f0aefni\u00f0 er undir \u00e1lagi \u00e6tti eftirlitskerfi frumuhringsins a\u00f0 virkjast til a\u00f0 koma \u00ed veg fyrir \u00f3heftan frumuv\u00f6xt. Eftirlitspr\u00f3teini\u00f0 P53 gegnir lykilhlutverki \u00ed a\u00f0 var\u00f0veita erf\u00f0amengi\u00f0 me\u00f0 \u00fev\u00ed a\u00f0 stu\u00f0la a\u00f0 st\u00f6\u00f0vun frumuhringsins og st\u00fdr\u00f0um frumudau\u00f0a \u00feegar erf\u00f0aefni\u00f0 er undir \u00e1lagi.<\/p>\n

Umritunar\u00fe\u00e1tturinn MITF gegnir lykilhlutverki \u00ed \u00feroskun og lifun litfrumna.\u00a0 Pr\u00f3teini\u00f0 er yfirtj\u00e1\u00f0 \u00ed 10-20% af sortu\u00e6xlum \u00fear sem \u00fea\u00f0 stu\u00f0lar a\u00f0 fj\u00f6lgun krabbameinsfrumna. Hlutverk MITF \u00ed \u00f6\u00f0rum vefjum er hins vegar l\u00edtt rannsaka\u00f0. Me\u00f0 \u00feessari ranns\u00f3kn s\u00fdnum vi\u00f0 a\u00f0 MITF gegnir mikilv\u00e6gu hlutverki \u00ed a\u00f0 vi\u00f0halda st\u00f6\u00f0ugleika erf\u00f0amengisins \u00ed \u00fdmsum frumul\u00ednum. \u00deegar MITF er slegi\u00f0 ni\u00f0ur \u00ed beinsarkmeinsfrumul\u00ednunni U2OS sj\u00e1st sk\u00fdr merki um DNA-eftirmyndunar\u00e1lag, litningaskemmdir og galla \u00ed DNA-vi\u00f0ger\u00f0um. \u00deetta lei\u00f0ir svo til P53 upps\u00f6fnunar, st\u00f6\u00f0vunar \u00ed G1 fasa frumuhringsins og a\u00f0 lokum st\u00fdr\u00f0s frumudau\u00f0a. Vi\u00f0 s\u00fdnum einnig a\u00f0 P53 upps\u00f6fnuninni er mi\u00f0la\u00f0 \u00ed gegnum LATS2, lykilk\u00ednasa \u00ed Hippo-ferlinum. Ni\u00f0urst\u00f6\u00f0ur \u00feessa verkefnis benda til \u00feess a\u00f0 hlutverk MITF \u00ed vi\u00f0haldi \u00e1 st\u00f6\u00f0ugleika erf\u00f0aefnisins s\u00e9 ekki takmarka\u00f0 vi\u00f0 litfrumur \u00fear sem skortur \u00e1 pr\u00f3teininu veldur \u00f3st\u00f6\u00f0ugleika \u00ed erf\u00f0amenginu \u00ed frumul\u00ednum \u00far \u00fdmsum vefjum. Ni\u00f0urst\u00f6\u00f0urnar s\u00fdna einnig tengsl milli MITF og Hippo-ferilsins sem oft hefur \u00f3e\u00f0lilega virkni \u00ed krabbameinum.<\/p>\n

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

Genome instability is a common feature of most cancer types. DNA damage is an important source of genome instability wherein DNA double strand breaks (DSBs) are particularly genotoxic as both strands of the DNA molecule are severed, risking loss of genetic material. Replication stress is another major source of genome instability. Unresolved replication stress can cause DNA double strand breaks (DSBs) and other chromosome aberrations, which can dramatically impact normal cell physiology. In cases of genotoxic stress, the cell cycle checkpoints are activated to prevent progression of potentially malignant cells. The cell cycle checkpoint protein P53 plays a central role in preserving genome integrity by facilitating cell cycle arrest and apoptosis in the presence of genotoxic stress. \u00a0<\/p>\n

Microphthalmia associated transcription factor (MITF) is crucial for melanocyte development and survival, and a major melanoma oncogene, amplified in 10-20% of melanomas. Studies on the role of MITF in other tissues are, however, scarce. Here we demonstrate that MITF has an important role in maintaining genome stability beyond the melanocyte lineage. MITF knockdown in the osteosarcoma cell line U2OS shows strong signs of replication stress, chromosomal abnormalities and defects in DNA DSB repair, which results in P53 mediated G1 arrest and apoptosis. Moreover, we show that MITF depletion activates P53 via Large tumor suppressor kinase 2 (LATS2) a key kinase in the Hippo pathway. Our findings indicate that the genome maintenance function of MITF is not limited to the melanocyte linage, as MITF knockdown caused genome instability across different cell types. Collectively, this study highlights the role of MITF as a non-melanocyte specific genome maintenance factor and uncovers a potential connection between MITF and the Hippo pathway, which is frequently dysregulated in cancer.\u00a0<\/p>\n

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

Dr\u00edfa Hrund Gu\u00f0mundsd\u00f3ttir er f\u00e6dd \u00e1ri\u00f0 1983 \u00ed Reykjav\u00edk. H\u00fan \u00fatskrifa\u00f0ist af raungreinabraut Menntask\u00f3lans vi\u00f0 Hamrahl\u00ed\u00f0 \u00e1ri\u00f0 2004. Dr\u00edfa lauk B.Sc. pr\u00f3fi \u00ed l\u00edffr\u00e6\u00f0i fr\u00e1 H\u00e1sk\u00f3la \u00cdslands \u00e1ri\u00f0 2015 og M.Sc. gr\u00e1\u00f0u \u00ed l\u00edf- og l\u00e6knav\u00edsindum fr\u00e1 sama sk\u00f3la \u00e1ri\u00f0 2017. Hausti\u00f0 2018 h\u00f3f Dr\u00edfa vinnu vi\u00f0 doktorsranns\u00f3kn s\u00edna. Ranns\u00f3knarverkefni\u00f0 hlaut styrk \u00far Ranns\u00f3knarsj\u00f3\u00f0i \u00edslands og Ranns\u00f3knarsj\u00f3\u00f0i Krabbameinsf\u00e9lagsins. Samhli\u00f0a doktorsn\u00e1mi hefur Dr\u00edfa sinnt kennslu vi\u00f0 L\u00e6knadeild og L\u00edf- og umhverfisv\u00edsindadeild H\u00e1sk\u00f3la \u00cdslands. \u00c1samt \u00fev\u00ed sat h\u00fan \u00ed stj\u00f3rn L\u00edfv\u00edsindaseturs sem fulltr\u00fai \u00a0doktorsnema 2019-2020. Foreldrar Dr\u00edfu eru Gu\u00f0mundur H\u00f3lm Indri\u00f0ason og Vilhelm\u00edna Halla Gu\u00f0mundsd\u00f3ttir. Eiginma\u00f0ur Dr\u00edfu er Gunnar Fri\u00f0rik Hermundarson og eiga \u00feau saman b\u00f6rnin Freyju D\u00eds, Heklu Soff\u00edu, Brynju Lill og Baldur Loga.<\/p>\n<\/div><\/div>","protected":false},"featured_media":5707,"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":"2024-11-19T09:00:00+00:00","_phd_date_end":"2024-11-19T12:00:00+00:00","_phd_location":"A\u00f0albygging H\u00e1t\u00ed\u00f0asalur","_phd_admission":"A\u00f0gangur \u00f3keypis","_phd_thesis_title":"Litfrumu \u00f3s\u00e9rt\u00e6kt hlutverk MITF \u00ed va\u00f0haldi \u00e1 st\u00f6\u00f0ugleika erf\u00f0aefnisins. 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