{"id":5983,"date":"2026-10-19T09:48:18","date_gmt":"2026-10-19T09:48:18","guid":{"rendered":"https:\/\/phd.hi.is\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-25-juni-kl-10-00-kimberley-jade-anderson\/"},"modified":"2026-10-19T09:48:18","modified_gmt":"2026-10-19T09:48:18","slug":"doktorsvorn-i-lif-og-laeknavisindum-25-juni-kl-10-00-kimberley-jade-anderson","status":"publish","type":"phd_defence","link":"https:\/\/phd.hi.is\/en\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-25-juni-kl-10-00-kimberley-jade-anderson\/","title":{"rendered":"Doktorsv\u00f6rn \u00ed l\u00edf- og l\u00e6knav\u00edsindum 25. j\u00fan\u00ed kl.10.00 &#8211; Kimberley Jade Anderson"},"content":{"rendered":"<div class=\"field-items\">\n<div class=\"field-item even\" property=\"content:encoded\">\n<p>Kimberley Jade Anderson ver 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>Mechanisms of transcriptional regulation in Waldenstr\u00f6m\u2019s macroglobulinemia and multiple myeloma. Sameindaferlar umritunar-stj\u00f3rnunar \u00ed Waldenstr\u00f6ms risagl\u00f3b\u00fal\u00ednbl\u00e6\u00f0i og merg\u00e6xlum.<\/strong><\/p>\n<p><strong>\u00a0<\/strong><\/p>\n<p>Andm\u00e6lendur eru dr. Zachary Hunter, lei\u00f0beinandi \u00ed l\u00e6knisfr\u00e6\u00f0i vi\u00f0 Harvard Medical School \u00ed Bandar\u00edkjunum, og dr. Inga Reynisd\u00f3ttir, kl\u00edn\u00edskur pr\u00f3fessor vi\u00f0 L\u00e6knadeild H\u00e1sk\u00f3la \u00cdslands.<\/p>\n<p>\u00a0<\/p>\n<p>Umsj\u00f3narkennari og lei\u00f0beinandi var dr. Erna Magn\u00fasd\u00f3ttir, d\u00f3sent vi\u00f0 L\u00e6knadeild. Auk hennar s\u00e1tu \u00ed doktorsnefnd \u00feau Arnar P\u00e1lsson, pr\u00f3fessor vi\u00f0 L\u00edf- og umhverfisv\u00edsindadeild, Eir\u00edkur Steingr\u00edmsson, \u00de\u00f3rarinn Gu\u00f0j\u00f3nsson og \u00de\u00f3runn Rafnar, en \u00feau starfa \u00f6ll sem pr\u00f3fessorar vi\u00f0 L\u00e6knadeild H\u00e1sk\u00f3la \u00cdslands.<\/p>\n<p>\u00a0<\/p>\n<p>Engilbert Sigur\u00f0sson, pr\u00f3fessor og forseti L\u00e6knadeildar, stj\u00f3rnar ath\u00f6fninni.<\/p>\n<p>\u00a0<\/p>\n<p><strong>\u00c1grip af ranns\u00f3kn<\/strong><\/p>\n<p><strong>\u00a0<\/strong><\/p>\n<p>Stj\u00f3rnferlar umritunar st\u00fdra \u00feroska B-fruma yfir \u00ed plasma-frumur, \u00fear sem st\u00f3rbrotnar breytingar \u00e1 umritunarferlum eiga s\u00e9r sta\u00f0. \u00deessar breytingar eru h\u00e1\u00f0ar fj\u00f6lm\u00f6rgum \u00fe\u00e1ttum, en \u00fear \u00e1 me\u00f0al er umritunar\u00fe\u00e1tturinn \u201cB lymphocyte- induced maturation protein-1\u201d (BLIMP1), auk ferla sem stj\u00f3rna umframerf\u00f0am\u00f6rkunum. \u00cd \u00feessari ritger\u00f0 er l\u00fdst tveimur verkefnum sem sko\u00f0a sameindaferla umritunarstj\u00f3rnar \u00ed krabbameinum m\u00f3tefnaseytandi fruma.<\/p>\n<p>Waldenstr\u00f6ms risagl\u00f3b\u00fal\u00ednbl\u00e6\u00f0i er krabbamein m\u00f3tefnaseytandi fruma \u00ed beinmerg sem hafa svipger\u00f0 eitil- og plasmafruma. Umritunar\u00fe\u00e1tturinn BLIMP1 er mikilv\u00e6gur fyrir seytingu m\u00f3tefna en hlutverk hans \u00ed Waldenstr\u00f6ms risagl\u00f3b\u00fal\u00ednbl\u00e6\u00f0i hefur \u00fe\u00f3 ekki veri\u00f0 rannsaka\u00f0. \u00cd \u00feessari ranns\u00f3kn er s\u00fdnt fram \u00e1 a\u00f0 frumur Waldenstr\u00f6ms risagl\u00f3b\u00fal\u00ednbl\u00e6\u00f0is eru h\u00e1\u00f0ar BLIMP1 til a\u00f0 lifa. Ranns\u00f3knir \u00e1 plasmabl\u00f6stum m\u00fasa og m\u00f3tefnaseytandi frumum hafa bent til a\u00f0 b\u00e6\u00f0i bein- sem og erf\u00f0afr\u00e6\u00f0ileg v\u00edxlverkun s\u00e9 \u00e1 milli BLIMP1 og hist\u00f3numet\u00fdltransferasans \u201eenhancer of zeste homologue 2\u201c (EZH2). Ranns\u00f3kn \u00feessi s\u00fdnir \u00a0fram \u00e1 \u00e1\u00f0ur \u00f3skilgreint hlutverk BLIMP1 \u00ed a\u00f0 vi\u00f0halda pr\u00f3t\u00ednstyrk EZH2 \u00ed frumum Waldenstr\u00f6ms risagl\u00f3b\u00fal\u00ednbl\u00e6\u00f0is. Ni\u00f0ursl\u00e1ttur \u00e1 BLIMP1 og hindrun \u00e1 EZH2 s\u00fdndu fram \u00e1 a\u00f0 mikil sk\u00f6run er \u00ed markgenum \u00feessara tveggja \u00fe\u00e1tta. \u00der\u00e1tt fyrir \u00feessa sk\u00f6run bindast BLIMP1 og EZH2 \u00e1 mismunandi bindiset \u00ed erf\u00f0amenginu, en oft \u00e1 s\u00f6mu genin. \u00deetta bendir til \u00feess a\u00f0 sk\u00f6run \u00ed virkni \u00fe\u00e1ttanna s\u00e9 a\u00f0 mestu vegna samhli\u00f0a stj\u00f3rnunar \u00e1 umritun auk vi\u00f0halds BLIMP1 \u00e1 EZH2 fremur en a\u00f0 \u00feeir bindist saman vi\u00f0 litni. Loks er s\u00fdnt fram \u00e1 hlutverk BLIMP1 og EZH2 \u00ed a\u00f0 for\u00f0a frumum sj\u00fakd\u00f3msins fr\u00e1 frumudau\u00f0a af v\u00f6ldum n\u00e1tt\u00farulegra dr\u00e1psfruma, auk stj\u00f3rnunar \u00e1 frumuhringnum. \u00deessar uppg\u00f6tvanir veita n\u00fdja inns\u00fdn inn \u00ed meinger\u00f0 Waldenstr\u00f6ms risagl\u00f3b\u00fal\u00ednbl\u00e6\u00f0is.<\/p>\n<p>Einstofna m\u00f3tefnah\u00e6kkun, e\u00f0a \u201emonoclonal gammopathy of undetermined significance\u201c (MGUS) er g\u00f3\u00f0kynja forstig merg\u00e6xla. Um 0,5-1% MGUS tilfella \u00fer\u00f3ast yfir \u00ed merg\u00e6xli \u00e1rlega og n\u00faverandi vi\u00f0mi\u00f0 sem notast er vi\u00f0 til a\u00f0 sp\u00e1 fyrir um \u00e1h\u00e6ttuna \u00e1 \u00feessari fram\u00fer\u00f3un eru \u00f3fulln\u00e6gjandi. \u00deeir ferlar sem hafa \u00e1hrif \u00e1 \u00fea\u00f0 a\u00f0 frumur breytist \u00far MGUS \u00ed merg\u00e6xli eru ekki vel \u00feekktir. Ranns\u00f3knir \u00e1 tj\u00e1ningarmynstrum hafa ekki bent til st\u00f3rfellds munar \u00ed umritun \u00e1 milli \u00feessara tveggja stiga. Ein lei\u00f0 til \u00feess a\u00f0 afhj\u00fapa n\u00fd merki er me\u00f0 \u00fev\u00ed a\u00f0 l\u00edta \u00e1 mismunandi virkjun eflira\u00f0a sem geta gefi\u00f0 til kynna breytingu \u00e1 e\u00f0li fruma jafnvel \u00ed fjarveru samsvarandi breytinga \u00ed genatj\u00e1ningu. H\u00e6gt er a\u00f0 bera kennsl \u00e1 mismunandi virkja\u00f0ar eflira\u00f0ir me\u00f0 tilvist mismunandi markana \u00e1 hist\u00f3num og umritunum eflira\u00f0a RNA (eRNA). \u00cd ranns\u00f3kninni er sett upp vinnuferli til \u00feess a\u00f0 rannsaka hist\u00f3num\u00f6rk \u00e1 eflir\u00f6\u00f0um og st\u00fdrlum auk vinnuferils fyrir RNA ra\u00f0greiningu \u00e1 heildar RNA \u00far frumum me\u00f0 \u00fev\u00ed a\u00f0 nota l\u00e1gan fj\u00f6lda fruma \u00far sj\u00faklingum me\u00f0 einstofna m\u00f3tefnah\u00e6kkun og merg\u00e6xlum sem upphafsefnivi\u00f0. \u00deessar a\u00f0fer\u00f0ir m\u00e1 nota \u00ed framt\u00ed\u00f0inni til \u00feess a\u00f0 bera kennsl \u00e1 \u00fe\u00e6tti sem hafa forsp\u00e1rgildi um sj\u00fakd\u00f3msframvindu MGUS og merg\u00e6xla.<\/p>\n<p><strong>\u00a0<\/strong><\/p>\n<p><strong>Abstract<\/strong><\/p>\n<p><strong>\u00a0<\/strong><\/p>\n<p>Transcriptional regulatory mechanisms drive the maturation of B cells to plasma cells, with a dramatic transcriptional rewiring taking place during the transition. This rewiring is dependent on a number of factors, including the transcription factor B lymphocyte induced maturation protein 1 (BLIMP1), and epigenetic mechanisms, amongst others. In this thesis, I present two projects investigating mechanisms of transcriptional regulation in antibody-secreting cell malignancies.<\/p>\n<p>Waldenstr\u00f6m\u2019s macroglobulinemia is a cancer of antibody-secreting lymphoplasmacytic cells in the bone marrow. The transcription factor BLIMP1 is important for antibody secretion and yet its role has not been studied in Waldenstr\u00f6m\u2019s macroglobulinemia. Here I demonstrate that Waldenstr\u00f6m\u2019s macroglobulinemia cell lines rely on BLIMP1 for survival. Studies in mouse plasmablasts and antibody secreting cells have suggested both a physical and genetic interaction between BLIMP1 and the histone methyltransferase enhancer of zeste homologue 2 (EZH2). In this study I reveal a novel role of BLIMP1 maintaining the protein levels of EZH2 in Waldenstr\u00f6m\u2019s macroglobulinemia. BLIMP1 knock-down and EZH2 inhibition reveal a large overlap in transcriptional targets of the two factors. Despite this, BLIMP1 and EZH2 bind to the genome at mostly distinct sites, although often on the same genes, indicating that the functional overlap of the two factors is mostly due to parallel transcriptional regulation and through maintenance of EZH2 by BLIMP1, rather than through co-binding to chromatin. Finally, I uncover novel roles for BLIMP1 and EZH2 in evasion from natural killer (NK) cell mediated cytotoxicity and regulation of the cell cycle. These findings provide novel insights into the pathology of Waldenstr\u00f6m\u2019s macroglobulinemia.<\/p>\n<p>Multiple myeloma is preceded by the pre-malignant monoclonal gammopathy of undetermined significance (MGUS). Around 0.5-1% of MGUS cases progress to myeloma each year and current standards for predicting the risk of progression are inadequate. The drivers of the transition from MGUS to multiple myeloma are still not well understood, and gene expression profiling studies have failed to identify major transcriptional differences between the two stages. One opportunity for uncovering novel markers is in the study of differential activation of transcriptional enhancers, which can indicate changes in cellular states even without corresponding gene expression changes. Differentially activated enhancers can be identified by the presence of different histone modifications and transcribed enhancer RNA (eRNA). Here, I establish a protocol for profiling histone modifications at enhancer and promoter regions and for total RNAseq using small numbers of cells from MGUS and myeloma patient material. These techniques may be used in the future to identify novel prognostic markers for MGUS and multiple myeloma.<\/p>\n<p><strong>\u00a0<\/strong><\/p>\n<p><strong>Um doktorsefni\u00f0<\/strong><\/p>\n<p>\u00a0<\/p>\n<p>Kimberley Jade Anderson \u00fatskrifa\u00f0ist me\u00f0 BSc-gr\u00e1\u00f0u \u00ed l\u00e6knav\u00edsindum me\u00f0 fyrstu \u00e1g\u00e6tiseinkunn fr\u00e1 University of New South Wales \u00ed Sydney, \u00c1stral\u00edu \u00e1ri\u00f0 2013. H\u00fan lauk \u201chonours research\u201d \u00e1ri s\u00ednu \u00e1 ranns\u00f3knarstofu Jenny Y. Wang vi\u00f0 Children\u2019s Cancer Institute Austalia. Kimberley hefur unni\u00f0 a\u00f0 doktorsgr\u00e1\u00f0u \u00ed l\u00edf- og l\u00e6knav\u00edsindum hj\u00e1 L\u00edfv\u00edsindastofnun vi\u00f0 H\u00e1sk\u00f3la \u00cdslands fr\u00e1 \u00fev\u00ed \u00ed \u00e1g\u00fast 2014. Foreldrar hennar eru Mavis D\u2019Cruz og Ross Anderson. H\u00fan b\u00fdr me\u00f0 eiginmanni s\u00ednum, Arnari \u00d6ssuri Har\u00f0arsyni, og stj\u00fapd\u00f3ttur, Vord\u00edsi S\u00f3l \u00d6ssurard\u00f3ttur. Kimberley og Arnar eiga von \u00e1 barni \u00ed \u00e1gust 2019.<\/p>\n<p>\u00a0<\/p>\n<\/div><\/div>","protected":false},"featured_media":1174,"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":"2019-06-25T10:00:00+00:00","_phd_date_end":"2019-06-25T12:30:00+00:00","_phd_location":"Askja 132","_phd_admission":"A\u00f0gangur \u00f3keypis","_phd_thesis_title":"Mechanisms of transcriptional regulation in Waldenstr\u00f6m\u2019s macroglobulinemia and multiple myeloma. 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