{"id":5971,"date":"2026-10-19T09:48:16","date_gmt":"2026-10-19T09:48:16","guid":{"rendered":"https:\/\/phd.hi.is\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-eirikur-briem\/"},"modified":"2026-10-19T09:48:16","modified_gmt":"2026-10-19T09:48:16","slug":"doktorsvorn-i-lif-og-laeknavisindum-eirikur-briem","status":"publish","type":"phd_defence","link":"https:\/\/phd.hi.is\/en\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-eirikur-briem\/","title":{"rendered":"Doktorsv\u00f6rn \u00ed l\u00edf- og l\u00e6knav\u00edsindum &#8211; Eir\u00edkur Briem"},"content":{"rendered":"<div class=\"field-items\">\n<div class=\"field-item even\" property=\"content:encoded\">\n<p>\u00deri\u00f0judaginn 3. j\u00fal\u00ed ver Eir\u00edkur Briem doktorsritger\u00f0 s\u00edna \u00ed l\u00edf- og l\u00e6knav\u00edsindum vi\u00f0 L\u00e6knadeild H\u00e1sk\u00f3la \u00cdslands. Ritger\u00f0in ber heiti\u00f0: <strong>Hlutverk microRNA \u00ed formger\u00f0 brj\u00f3stkirtils og bandvefsumbreytingu \u00feekjuvefjar.<\/strong> <strong>Functional role of microRNAs in breast morphogenesis and epithelial to mesenchymal transition<\/strong><strong>.<\/strong><\/p>\n<p>Andm\u00e6lendur eru dr. James B. Lorens, pr\u00f3fessor vi\u00f0 h\u00e1sk\u00f3lann \u00ed Bergen, og dr. Zophon\u00edas Oddur J\u00f3nsson, pr\u00f3fessor \u00ed sameindaerf\u00f0afr\u00e6\u00f0i vi\u00f0 L\u00edf- og umhverfisv\u00edsindadeild H\u00e1sk\u00f3la \u00cdslands.<\/p>\n<p>Umsj\u00f3narkennari og lei\u00f0beinandi var \u00de\u00f3rarinn Gu\u00f0j\u00f3nsson, pr\u00f3fessor vi\u00f0 L\u00e6knadeild H\u00e1sk\u00f3la \u00cdslands og me\u00f0lei\u00f0beinandi var Magn\u00fas Karl Magn\u00fasson, pr\u00f3fessor vi\u00f0 s\u00f6mu deild. Auk \u00feeirra s\u00e1tu \u00ed doktorsnefnd Erna Magn\u00fasd\u00f3ttir, d\u00f3sent vi\u00f0 L\u00e6knadeild H\u00e1sk\u00f3la \u00cdslands, Hans T\u00f3mas Bj\u00f6rnsson, yfirl\u00e6knir \u00e1 Landsp\u00edtala og \u00de\u00f3runn Rafnar, yfirma\u00f0ur krabbameinsranns\u00f3kna hj\u00e1 \u00cdslenskri erf\u00f0agreiningu.<\/p>\n<p>Engilbert Sigur\u00f0sson, pr\u00f3fessor, deildarforseti L\u00e6knadeildar, stj\u00f3rnar ath\u00f6fninni sem fer fram \u00ed \u00d6skju, stofu 132, og hefst kl. 13:00.<\/p>\n<p><strong>\u00c1grip af ranns\u00f3kn<\/strong><\/p>\n<p>Brj\u00f3stakrabbamein \u00e1 uppt\u00f6k \u00ed \u00feekjufrumum \u00ed endum grein\u00f3ttra kirtilganga. \u00cd \u00e6xlisvexti n\u00fdta krabbameinsfrumur s\u00e9r ferli sem kallast bandvefsumbreyting \u00feekjuvefjar (e. epithelial to mesenchymal transition, EMT) til a\u00f0 skr\u00ed\u00f0a \u00ed gegnum bandvef \u00ed \u00e1tt a\u00f0 sog\u00e6\u00f0um og e\u00f0a h\u00e1r\u00e6\u00f0um sem \u00fe\u00e6r n\u00fdta s\u00e9r til meinvarpamyndunar til annarra l\u00edff\u00e6ra. Aukinn skilningur \u00e1 ferlum sem st\u00fdra grein\u00f3ttri formger\u00f0 og EMT er mikilv\u00e6gur \u00fear sem s\u00fa vitneskja getur varpa\u00f0 lj\u00f3si \u00e1 fyrstu skref \u00ed myndun brj\u00f3stakrabbameina. \u00cd verkefninu var notast vi\u00f0 brj\u00f3stastofnfrumul\u00ednuna D492 sem myndar kirtilganga og kirtilber \u00ed \u00fer\u00edv\u00ed\u00f0ri frumur\u00e6kt. \u00deegar D492 er r\u00e6ktu\u00f0 \u00ed \u00fer\u00edv\u00ed\u00f0ri samr\u00e6kt me\u00f0 \u00e6\u00f0a\u00feelsfrumum eykst geta hennar til grein\u00f3ttrar formmyndunar og EMT. D492M frumul\u00ednan er komin fr\u00e1 D492 \u00ed gegnum EMT. \u00a0\u00cd doktorsverkefninu var genatj\u00e1ningarmynstur D492 og D492M \u00ed myndun grein\u00f3ttrar formger\u00f0ar og EMT rannsaka\u00f0. S\u00fdnt var fram \u00e1 mikinn mun \u00ed tj\u00e1ningu sm\u00e1s\u00e6rra RNA sameinda (miRNA) milli D492 og D492M. Genatj\u00e1ning sem einkennir \u00feekjuvef er r\u00edkjandi \u00ed D492 en genatj\u00e1ning bandvefs er r\u00edkjandi \u00ed D492M. Vi\u00f0 greiningu miRNA tj\u00e1ningar kom \u00ed lj\u00f3s a\u00f0 mest minnkun \u00ed D492M var \u00e1 tj\u00e1ningu miRNA sem tilheyra miRNA-200 fj\u00f6lskyldunni \u00e1samt miR-203a. \u00deessi miRNA gegna mikilv\u00e6gu hlutverki \u00ed vi\u00f0haldi \u00feekjuvefsformger\u00f0ar og minnku\u00f0 tj\u00e1ning \u00feeirra hefur veri\u00f0 tengd EMT. \u00deegar miR-200c-141 var yfirtj\u00e1\u00f0 \u00ed D492M olli \u00fea\u00f0 umbreytingu fr\u00e1 bandvefsformger\u00f0 yfir \u00ed kirtil\u00feekjuformger\u00f0. \u00deegar umritunar\u00fe\u00e1tturinn \u0394Np63 var yfirtj\u00e1\u00f0ur \u00ed D492MmiR-200c-141 voru stofnfrumueiginleikar frumul\u00ednunnar endurheimtir. Vi\u00f0 ranns\u00f3knir \u00e1 hlutverki miR-203a \u00ed grein\u00f3ttri formger\u00f0 og EMT kom \u00ed lj\u00f3s a\u00f0 tj\u00e1ning miR-203a \u00ed D492 eykst vi\u00f0 myndun kirtilberja samhli\u00f0a aukinni \u00feroskun og s\u00e9rh\u00e6fingu frumanna. \u00deegar miR-203a var yfirtj\u00e1\u00f0 \u00ed D492M breyttist svipger\u00f0 a\u00f0 hluta til \u00ed \u00e1tt til \u00feekjuvefsformger\u00f0ar. Ni\u00f0urst\u00f6\u00f0ur \u00e1 samanbur\u00f0i genatj\u00e1ningar milli D492M og D492MmiR-203a leiddu til uppg\u00f6tvunar \u00e1 peroxidasin (PXDN) sem markgens miR-203a. PXDN getur mynda\u00f0 krosstengi \u00ed kollagen IV (COL4A1) sem er mikilv\u00e6gt fyrir st\u00f6\u00f0ugleika grunnhimnunar. Einnig var s\u00fdnt fram \u00e1 a\u00f0 hindrun \u00e1 pr\u00f3t\u00edn t\u00fdr\u00f3s\u00edn fosfatasa, \u00e1n-vi\u00f0taka ger\u00f0ar 1 (PTP1B) trufla\u00f0i millifrumutengi og olli frumudau\u00f0a \u00ed D492 frumum. Samanteki\u00f0, \u00fe\u00e1 hefur verkefni\u00f0 varpa\u00f0 lj\u00f3si \u00e1 mikilv\u00e6ga ferla sem koma a\u00f0 st\u00fdringu grein\u00f3ttrar formger\u00f0ar og EMT \u00ed brj\u00f3stkirtli.<\/p>\n<p><strong>Abstract<\/strong><\/p>\n<p>Gene expression in branching morphogenesis and epithelial to mesenchymal transition (EMT) was investigated in the breast epithelial progenitor cell line D492. D492 generates luminal- and myoepithelial cells and in three-dimensional reconstituted basement membrane matrix (3D-rBM) it generates structures reminiscent of the terminal duct lobular units (TDLUs) of the breast. When co-cultured with endothelial cells, subset of D492 cells undergo EMT. We have established an endothelial-induced mesenchymal subline from D492 referred to as D492M. In this work, D492 and D492M was cultivated in 3D-rBM as a model to investigate gene expression of noncoding RNAs (mainly miRNAs) and protein coding genes during different stages of branching morphogenesis and in EMT. Of the most downregulated miRNAs in D492M were members of the miR-200 family and miR-203a. These miRNAs have been shown to be important for epithelial integrity and their downregulation linked to EMT. Overexpression of miR-200c-141 in D492M demonstrated reversion towards the epithelial phenotype. When the transcription factor \u0394Np63 was overexpressed in D492MmiR-200c-141 branching morphogenesis was restored. Next the role of miRNA-203a was studied, its expression during branching and EMT, and the identification of potential novel targets of miR-203a. Interestingly, miR-203a showed a gradual increase in expression accompanied by increased complexity of the branching structures. MiR-203a was not detected in D492M and when it was overexpressed in D492M, cells partially changed phenotype towards the epithelial phenotype. Gene expression analysis of D492M and D492MmiR-203a revealed peroxidasin (PXDN), a collagen IV cross-linking agent, as a novel target of miR-203a. Treatment of the D492 and D492M with a specific PTP1B inhibitor was also shown to induced anoikis with D492M being more sensitive to PTP1B inhibition. Collectively, in this work isogenic breast epithelial cell lines were used to explore processes important in branching morphogenesis and EMT.<\/p>\n<p><strong>Um doktorsefni\u00f0 \u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 <\/strong><\/p>\n<p>Eir\u00edkur Briem er f\u00e6ddur \u00ed Reykjav\u00edk 11. apr\u00edl 1979. Eir\u00edkur lauk st\u00fadentspr\u00f3fi fr\u00e1 Menntask\u00f3lanum \u00ed Reykjav\u00edk 1999, B.Sc.-pr\u00f3fi\u00a0 \u00ed l\u00edffr\u00e6\u00f0i fr\u00e1 H\u00e1sk\u00f3la \u00cdslands 2002 og MS-pr\u00f3fi \u00ed l\u00edf- og matv\u00e6lat\u00e6kni fr\u00e1 H\u00e1sk\u00f3lanum \u00ed Lundi 2005. Eir\u00edkur hefur fj\u00f6lbreytta reynslu af ranns\u00f3knum og var ranns\u00f3knarstofustj\u00f3ri hj\u00e1 Johns Hopkins University \u00fear sem hann vann a\u00f0 uppbyggingu ranns\u00f3knarstofu \u00ed ra\u00f0greiningar- og \u00f6rfl\u00f6gut\u00e6kni. Eir\u00edkur vann \u00e1\u00f0ur hj\u00e1 Roche NimbleGen og hj\u00e1 Prokaria. \u00cd dag starfar Eir\u00edkur sem deildarstj\u00f3ri Erf\u00f0a- og sameindal\u00e6knisfr\u00e6\u00f0ideildar \u00e1 Lansp\u00edtala.<br \/> Foreldrar Eir\u00edks eru Gu\u00f0r\u00fan R. Briem og Eir\u00edkur Briem. Samb\u00fdliskona Eir\u00edks er Hanna Krist\u00edn P\u00e9tursd\u00f3ttir og eiga \u00feau fj\u00f6gur b\u00f6rn.<\/p>\n<\/div><\/div>","protected":false},"featured_media":1140,"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":"2018-07-03T13:00:00+00:00","_phd_date_end":"2018-07-03T16:00:00+00:00","_phd_location":"Askja Stofa 132","_phd_admission":"A\u00f0gangur \u00f3keypis","_phd_thesis_title":"Hlutverk microRNA \u00ed formger\u00f0 brj\u00f3stkirtils og bandvefsumbreytingu \u00feekjuvefjar. 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