{"id":6003,"date":"2026-10-19T09:48:21","date_gmt":"2026-10-19T09:48:21","guid":{"rendered":"https:\/\/phd.hi.is\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-stefan-thor-hermanowicz\/"},"modified":"2026-10-19T09:48:21","modified_gmt":"2026-10-19T09:48:21","slug":"doktorsvorn-i-lif-og-laeknavisindum-stefan-thor-hermanowicz","status":"publish","type":"phd_defence","link":"https:\/\/phd.hi.is\/en\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-stefan-thor-hermanowicz\/","title":{"rendered":"Doktorsv\u00f6rn \u00ed l\u00edf- og l\u00e6knav\u00edsindum &#8211; Stef\u00e1n \u00de\u00f3r Hermanowicz"},"content":{"rendered":"<div class=\"field-items\">\n<div class=\"field-item even\" property=\"content:encoded\">\n<p>Mi\u00f0vikudaginn 15. ma\u00ed ver Stef\u00e1n \u00de\u00f3r Hermanowicz 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>The Epigenetic Silencing of ALKBH3 and the<\/strong><\/p>\n<p><strong>Epitranscriptomic Regulation of DNA Repair. Sviperf\u00f0abreytingar \u00e1 ALKBH3 og \u00e1hrif sviperf\u00f0a \u00e1 RNA \u00ed stj\u00f3rnun \u00e1 DNA vi\u00f0ger\u00f0.<\/strong><\/p>\n<p>Andm\u00e6lendur eru dr. Arne Klungland, pr\u00f3fessor vi\u00f0 H\u00e1sk\u00f3lasj\u00fakrah\u00fasi\u00f0 \u00ed \u00d3sl\u00f3, og Dr. Zophon\u00edas O. J\u00f3nsson, pr\u00f3fessor vi\u00f0 L\u00edf- og umhverfisv\u00edsindadeild H\u00e1sk\u00f3la \u00cdslands.\u00a0<\/p>\n<p>Umsj\u00f3narkennari var dr. Stef\u00e1n \u00de. Sigur\u00f0sson, d\u00f3sent vi\u00f0 L\u00e6knadeild, og lei\u00f0beinandi var dr. \u00deorkell Gu\u00f0j\u00f3nsson, n\u00fddoktor vi\u00f0 L\u00e6knadeild.\u00a0Auk \u00feeirra s\u00e1tu \u00ed doktorsnefnd dr. J\u00f3n Gunnlaugur J\u00f3nasson, pr\u00f3fessor vi\u00f0 L\u00e6knadeild, dr. \u00d3lafur Andri Stef\u00e1nsson, pr\u00f3fessor og dr. Claudia Lukas, pr\u00f3fessor vi\u00f0 H\u00e1sk\u00f3lann \u00ed Kaupmannah\u00f6fn.<\/p>\n<p>Dr. Ingibj\u00f6rg Har\u00f0ard\u00f3ttir pr\u00f3fessor og varaforseti L\u00e6knadeildar, stj\u00f3rnar ath\u00f6fninni sem fer fram \u00ed H\u00e1t\u00ed\u00f0asal H\u00e1sk\u00f3la \u00cdslands og hefst kl. 14:00.<\/p>\n<p><strong>\u00c1grip af ranns\u00f3kn<\/strong><\/p>\n<p>Eitt af megineinkennum krabbameinsfruma er \u00f3st\u00f6\u00f0ugt erf\u00f0amengi. \u00deessi \u00f3st\u00f6\u00f0ugleiki er talinn stafa af upps\u00f6fnun DNA skemmda sem fruman n\u00e6r ekki a\u00f0 gera vi\u00f0. Til a\u00f0 koma \u00ed veg fyrir a\u00f0 \u00feetta gerist b\u00fdr fruman yfir mj\u00f6g \u00f6flugu eftirlitskerfi sem skynjar og bregst vi\u00f0 DNA skemmdum. Gallar \u00ed mikilv\u00e6gum genum innan \u00feessa kerfis eru algengir \u00ed krabbameinsfrumum. \u00cd sumum tilfellum er h\u00e6gt a\u00f0 nota sl\u00edka galla til a\u00f0 a\u00f0greina krabbameinsfrumur fr\u00e1 heilbrig\u00f0um frumum, og n\u00fdta \u00ed lyfjame\u00f0fer\u00f0. ALKBH3 er d\u00edoxigenasi sem tekur \u00fe\u00e1tt \u00ed vi\u00f0ger\u00f0 \u00e1 alky\u0301lerandi DNA skemmdum. Ranns\u00f3knir okkar \u00e1 g\u00f6gnum fr\u00e1 \u201dThe Cancer Genome Atlas\u201d s\u00fdndu a\u00f0 st\u00fdrilsv\u00e6\u00f0i innan ALKBH3 gensins er met\u00fdlera\u00f0 \u00ed um 20% brj\u00f3stakrabbameina. \u00deetta hefur \u00ed f\u00f6r me\u00f0 s\u00e9r minnka\u00f0a ALKBH3 mRNA tj\u00e1ningu og \u00fear me\u00f0 minni framlei\u00f0slu \u00e1\u00a0 ALKBH3 pr\u00f3teini. Greining \u00e1 s\u00fdnum \u00far \u00edslenska \u00fe\u00fd\u00f0inu leiddu \u00ed lj\u00f3s a\u00f0 t\u00ed\u00f0ni ALKBH3 met\u00fdlunar er um 10% \u00ed brj\u00f3stakrabbameini. Samanbur\u00f0ur \u00e1 s\u00fdnum \u00far heilbrig\u00f0um vef og krabbameinsvef \u00far sama einstaklingi s\u00fdndu a\u00f0 ALKBH3 met\u00fdlun greinist bara \u00ed krabbameinsvef. \u00dear a\u00f0 auki er lifun verri hj\u00e1 \u00feeim brj\u00f3stakrabbameinssj\u00faklingum sem hafa miki\u00f0 magn met\u00fdlunar \u00e1 ALKBH3 st\u00fdrilsv\u00e6\u00f0inu. Frekari ranns\u00f3knir s\u00fdndu a\u00f0 tap \u00e1 ALKBH3 tj\u00e1ningu leiddi til minni tj\u00e1ningar \u00e1 mikilv\u00e6gum stj\u00f3rn\u00fe\u00e6tti \u00ed vi\u00f0ger\u00f0 \u00e1 mj\u00f6g alvarlegri ger\u00f0 DNA skemmda, tv\u00ed\u00fe\u00e1tta DNA rofi. Ni\u00f0urst\u00f6\u00f0ur \u00feessa verkefnis gefa til kynna a\u00f0 ALKBH3 hafi \u00e1hrif \u00e1 vi\u00f0ger\u00f0 \u00e1 tv\u00ed\u00fe\u00e1tta DNA rofi me\u00f0 \u00fev\u00ed a\u00f0 fjarl\u00e6gja met\u00fdlh\u00f3pa af mRNA sameind sem tj\u00e1ir pr\u00f3tein sem tekur \u00fe\u00e1tt \u00ed ferlinu. \u00dea\u00f0 a\u00f0 met\u00fdlun \u00e1 mRNA sameindum geti haft \u00e1hrif \u00e1 tj\u00e1ningu pr\u00f3teina er tilt\u00f6lulega n\u00fd uppg\u00f6tvun sem hefur \u00e1 sk\u00f6mmum t\u00edma vaki\u00f0 mikla athygli. \u00cd \u00feessu verkefni er \u00ed fyrsta skipti s\u00fdnt fram \u00e1 a\u00f0 DNA vi\u00f0ger\u00f0arpr\u00f3teini s\u00e9 stj\u00f3rna\u00f0 me\u00f0 sl\u00edkum h\u00e6tti. \u00dev\u00ed er mikilv\u00e6gt a\u00f0 skilgreina \u00feessa \u00e1\u00f0ur \u00f3\u00feekktu a\u00f0fer\u00f0 sem ALKBH3 notar til a\u00f0 stj\u00f3rna genatj\u00e1ningu til a\u00f0 auka skilning okkar \u00e1 l\u00edffr\u00e6\u00f0ilegum ors\u00f6kum krabbameina. \u00dear a\u00f0 auki m\u00e1 hugsanlega n\u00fdta \u00feessa n\u00fdju \u00feekkingu \u00e1 hlutverki ALKBH3 \u00ed \u00fer\u00f3un n\u00fdrra me\u00f0fer\u00f0ar\u00farr\u00e6\u00f0a.\u00a0<\/p>\n<p><strong>Abstract<\/strong><\/p>\n<p>The DNA damage response is crucial to maintaining the integrity of DNA and the health of a cell. Unrepaired lesions within the DNA can lead to genomic instability and potentially aid in the formation of diseases such as cancer. Some cancers possess dysfunctional DNA repair and chemotherapeutic treatments may aim to exploit this weakness that distinguishes cancer cells from normal healthy cells. ALKBH3 is a DNA repair protein involved in the repair of alkylation damage. Within The Cancer Genome Atlas we found that ALKBH3 contained a hyper-methylated promoter in 20% of breast cancers. This hyper-methylation, a form of epigenetic regulation, lead to a dramatic reduction of ALKBH3 mRNA expression and therefore a decrease in total ALKBH3 protein levels. We looked within a sample of Icelandic breast tumors and found they too possessed hyper-methylated promoters for ALKBH3. Importantly, this methylation occurs only within the tumor tissue, but not the normal tissue of the same patients. Additionally, patients who contained high levels of promoter methylation had statistically significant decreased survival. The project then explored the functional consequences of the absence of ALKBH3. We discovered that the knockdown of ALKBH3 causes a decrease in protein levels of a protein crucial in DNA double-strand break repair. We determined that this protein is regulated by ALKBH3 through a form of regulation called epitranscriptomics. Epitranscriptomics is a new field of study of how RNA fate is determined, largely through the addition and removal of methyl groups on RNA nucleotides. This project helps elucidate a potential contributing factor to cancer development as well as provide a potential target for chemotherapeutic treatment.<\/p>\n<p><strong>Um doktorsefni\u00f0<\/strong><\/p>\n<p>Stef\u00e1n \u00de\u00f3r Hermanowicz f\u00e6ddist \u00e1ri\u00f0 1989 \u00ed Ann Arbor \u00ed Michigan, Bandar\u00edkjunum. Hann lauk BS pr\u00f3fi \u00ed Human Biology fr\u00e1 University of California San Diego \u00e1ri\u00f0 2012. Stef\u00e1n flutti \u00fe\u00e1 til \u00cdslands og lauk M.Sc. pr\u00f3fi \u00ed l\u00edf- og l\u00e6knav\u00edsindum fr\u00e1 H\u00e1sk\u00f3la \u00cdslands \u00e1ri\u00f0 2015. Foreldrar Stef\u00e1ns eru Neal Hermanowicz og Dagn\u00fd \u00deorgilsd\u00f3ttir.<\/p>\n<\/div><\/div>","protected":false},"featured_media":1217,"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":"2019-05-15T14:00:00+00:00","_phd_date_end":"2019-05-15T17:00:00+00:00","_phd_location":"A\u00f0albygging H\u00e1t\u00ed\u00f0asalur","_phd_admission":"A\u00f0gangur \u00f3keypis","_phd_thesis_title":"The Epigenetic Silencing of ALKBH3 and the","_phd_source_url":"https:\/\/gamli.hi.is\/vidburdir\/doktorsvorn_i_lif_og_laeknavisindum_stefan_thor_hermanowicz","_phd_source_node_id":"316961","_phd_source_type":"vidburdir","_phd_member_id":212,"footnotes":""},"phd_school":[60,67],"phd_discipline":[70],"class_list":["post-6003","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\/6003","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\/6003\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/media\/1217"}],"wp:attachment":[{"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/media?parent=6003"}],"wp:term":[{"taxonomy":"phd_school","embeddable":true,"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/phd_school?post=6003"},{"taxonomy":"phd_discipline","embeddable":true,"href":"https:\/\/phd.hi.is\/en\/wp-json\/wp\/v2\/phd_discipline?post=6003"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}