{"id":6406,"date":"2026-10-19T09:48:52","date_gmt":"2026-10-19T09:48:52","guid":{"rendered":"https:\/\/phd.hi.is\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-juan-ouyang\/"},"modified":"2026-10-19T09:48:52","modified_gmt":"2026-10-19T09:48:52","slug":"doktorsvorn-i-lif-og-laeknavisindum-juan-ouyang","status":"publish","type":"phd_defence","link":"https:\/\/phd.hi.is\/en\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-juan-ouyang\/","title":{"rendered":"Doktorsv\u00f6rn \u00ed l\u00edf- og l\u00e6knav\u00edsindum Juan Ouyang"},"content":{"rendered":"
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Fimmtudaginn 19. j\u00fan\u00ed 2025 ver Juan Ouyang doktorsritger\u00f0 s\u00edna \u00ed l\u00edf- og l\u00e6knav\u00edsindum vi\u00f0 L\u00e6knadeild H\u00e1sk\u00f3la \u00cdslands. Ritger\u00f0in ber heiti\u00f0: \u00c1hrif utangenakerfisins \u00e1 DNA met\u00fdleringu \u00ed tauga\u00feroskam\u00f3deli. Investigating DNA methylation dynamics in normal and epigenetic machinery deficient neurodevelopment.<\/strong><\/p>\n

Andm\u00e6lendur eru dr. David Katz, pr\u00f3fessor vi\u00f0 Emory University \u00ed Atlanta, og \u00a0dr. Sigr\u00ed\u00f0ur Rut Franzd\u00f3ttir, d\u00f3sent vi\u00f0 L\u00edf- og umhverfisv\u00edsindadeild H\u00e1sk\u00f3la \u00cdslands.<\/p>\n

Umsj\u00f3narkennari og lei\u00f0beinandi var Hans T\u00f3mas Bj\u00f6rnsson, pr\u00f3fessor. A\u00f0rir \u00ed doktorsnefnd voru Erna Magn\u00fasd\u00f3ttir, d\u00f3sent, \u00d3lafur Magn\u00fasson, h\u00f3pstj\u00f3ri hj\u00e1 \u00cdE, og Ragnhildur \u00de\u00f3ra K\u00e1rad\u00f3ttir, pr\u00f3fessor.<\/p>\n

Eir\u00edkur Steingr\u00edmsson, pr\u00f3fessor vi\u00f0 L\u00e6knadeild stj\u00f3rnar ath\u00f6fninni sem fer fram \u00ed H\u00e1t\u00ed\u00f0asal H\u00e1sk\u00f3la \u00cdslands og hefst kl. 13.00.<\/p>\n

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

Utangenaerf\u00f0a\u00fe\u00e6ttir (e. epigenetic machinery, EM) gegna mikilv\u00e6gu hlutverki vi\u00f0 a\u00f0 stj\u00f3rna a\u00f0gengi litnis og hafa \u00feannig \u00e1hrif \u00e1 genatj\u00e1ningu. Mendelsk heilkenni utangenakerfisins (e. Mendelian disorders of the epigenetic machinery, MDEM) orsakast vegna st\u00f6kkbreytinga \u00ed EM genum og hafa einstaklingar me\u00f0 MDEM \u00fdmsar sameiginlegar svipger\u00f0ir, \u00fear \u00e1 me\u00f0al greindarsker\u00f0ingu og vaxtartruflun. Einstaklingar me\u00f0 MDEM s\u00fdna einnig fr\u00e1vik \u00ed DNA met\u00fdlun (DNAm) \u00ed bl\u00f3\u00f0frumum. Hins vegar er \u00f3lj\u00f3st hvort truflun \u00e1 DNAm s\u00e9 ors\u00f6k fyrir sameiginlegum svipger\u00f0um \u00feessara heilkenna. \u00deessi ritger\u00f0 hefur \u00fea\u00f0 a\u00f0 markmi\u00f0i a\u00f0 \u00fer\u00f3a l\u00edkan fyrir \u00feroskun taugafrumna og finna mikilv\u00e6ga DNA-met\u00fdlunarsta\u00f0i (DNAm) sem breytast \u00ed taugafrumul\u00edk\u00f6num vi\u00f0 tap \u00e1 EM-\u00fe\u00e1ttum.<\/p>\n

\u00cd \u00feessari ranns\u00f3kn t\u00f3kst a\u00f0 koma \u00e1 f\u00f3t l\u00edkani fyrir \u00feroskun taugafrumna. V\u00ed\u00f0t\u00e6k minnkun s\u00e1st \u00e1 met\u00fdlun \u00ed taugafrumum sem vanta\u00f0i Dnmt1 geni\u00f0 en litlar breytingar \u00ed \u00feeim sem vanta\u00f0i Kmt2a. Enn fremur fannst j\u00e1kv\u00e6\u00f0 fylgni \u00ed mis-tj\u00e1\u00f0um genum \u00ed frumum sem vanta\u00f0i hvort geni\u00f0 fyrir sig sem bendir til tengingu \u00ed virkni \u00feessara tveggja \u00fe\u00e1tta.<\/p>\n

Einnig var rannsaka\u00f0 DNAm mynstur \u00e1 kerfisbundinn h\u00e1tt \u00ed tauga\u00feroskam\u00f3delinu eftir \u00fatsl\u00e1tt \u00e1 46 utangenaerf\u00f0agenum. \u00de\u00f3tt tap \u00e1 sl\u00edkum EM genum leiddi almennt til v\u00e6gra DNAm breytinga, voru undantekningar \u00e1 \u00fev\u00ed eins og til d\u00e6mis \u00fatsl\u00e1ttur \u00e1 Dnmt1 og Dnmt3b sem s\u00fdndu mun meiri breytingar \u00e1\u00a0 DNAm. Me\u00f0 \u00fev\u00ed a\u00f0 n\u00fdta tilraunauppsetningu, \u00fear sem frumur voru fengnar \u00far F1 blendingsl\u00edkani tveggja m\u00fasa-arfger\u00f0a (B6J fa\u00f0ir \u00d7 FVB\/NJ m\u00f3\u00f0ir), voru greind sams\u00e6tus\u00e9rt\u00e6k mis-met\u00fdleru\u00f0 sv\u00e6\u00f0i (e. Allele-Specific DMRs, AS-DMRs) me\u00f0 \u00fev\u00ed a\u00f0 n\u00fdta einkirnabreytileika (e. single nucleotide polymorphisms, SNPs) milli arfger\u00f0anna til a\u00f0 a\u00f0greina sams\u00e6turnar. A\u00f0 lokum leiddi fasagreiningin \u00ed lj\u00f3s eitt markt\u00e6kt erf\u00f0amengis-breytt mismet\u00fdlera\u00f0 gen, sta\u00f0sett \u00ed 3\u00b4UTR \u00e1 Zic4 geninu, sem einnig s\u00fdndi breytingu \u00ed genatj\u00e1ningu vi\u00f0 \u00feroska taugafrumna.<\/p>\n

Ranns\u00f3knin s\u00fdnir mikilv\u00e6gi \u00feess a\u00f0 sam\u00fe\u00e6tta ONT og RNA ra\u00f0greiningu til a\u00f0 skilja samspil DNAm breytinga og genatj\u00e1ningar \u00ed vi\u00f0eigandi sj\u00fakd\u00f3mal\u00edkani (taugafrumum). \u00deessi sam\u00fe\u00e6tta n\u00e1lgun gerir kleift a\u00f0 greina sm\u00e1v\u00e6gilegar, en l\u00edffr\u00e6\u00f0ilega mikilv\u00e6ga breytileika sem g\u00e6tu n\u00fdst sem lyfjam\u00f6rk e\u00f0a greiningarmerki fyrir \u00feessa MDEM sj\u00fakd\u00f3ma \u00ed framt\u00ed\u00f0inni.<\/p>\n

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

Epigenetic machinery (EM) factors are essential for modulating chromatin states and regulating gene expression. The Mendelian disorders of the epigenetic machinery (MDEM), caused by mutations in the EM, often result in shared phenotypes, including intellectual disability and growth dysregulation. Many individuals with an MDEM diagnosis exhibit DNA methylation (DNAm) abnormalities in peripheral blood cells. However, whether DNAm dysregulation in MDEMs functionally links these two overlapping phenotypes remains unclear. This thesis aims to develop a neuronal development model and identify potentially functionally important DNAm loci that show changes across multiple EM deficient neuronal models.<\/p>\n

In this study, we successfully established a neuronal development model. We observed extensive global demethylation in Dnmt1KOs, whereas Kmt2aKOs exhibited relatively mild DNAm changes. Additionally, we uncovered a substantial overlap in differentially expressed genes (DEGs), with a strong positive correlation between the shared DEGs among the two.<\/p>\n

Beyond individual KO analyses, we systematically investigated DNAm patterns across all 46 EM-KOs. While most exhibited subtle DNAm alterations, notable exceptions included Dnmt1 and Dnmt3b, showed more sizable DNAm changes. Leveraging our experimental setup using cells derived from an F1 hybrid model (B6J paternal \u00d7 FVB\/NJ maternal), we were able to identify allele-specific differentially methylated regions (AS-DMRs) using single-nucleotide polymorphisms (SNPs), and using phasing analysis, we discovered a single genome-wide significant DMR located in the 3\u00b4UTR of Zic4, which was differentially expressed during neuronal maturation.<\/p>\n

These findings provide a valuable strategy for integrating ONT and RNA sequencing to investigate DNAm dynamics and gene expression changes in a disease-relevant model (neurons). This integrative approach enables the detection of subtle but biologically meaningful candidates that may serve as therapeutic targets or diagnostic markers for MDEMs.<\/p>\n

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

Juan Ouyang er f\u00e6dd \u00e1ri\u00f0 1997 \u00ed K\u00edna. H\u00fan lauk BSc-gr\u00e1\u00f0u fr\u00e1 Shaoyang-h\u00e1sk\u00f3la \u00ed l\u00edfverkfr\u00e6\u00f0i \u00e1ri\u00f0 \u00e1ri\u00f0 2017. H\u00fan var\u00f0i mastersritger\u00f0 tengda utangenaerf\u00f0um \u00ed Yangzhou-h\u00e1sk\u00f3la \u00e1ri\u00f0 2020. Juan kom s\u00ed\u00f0an til \u00cdslands \u00e1ri\u00f0 2021 er h\u00fan h\u00f3f doktorsn\u00e1m hj\u00e1 Hans T\u00f3masi Bj\u00f6rnssyni. Foreldrar hennar eru Dalian Ouyang og Xiaoe Wang, b\u00e6\u00f0i b\u00fasett \u00ed Yiyang \u00ed K\u00edna.\u00a0\u00a0<\/p>\n<\/div><\/div>","protected":false},"featured_media":5781,"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":"2025-06-19T13:00:00+00:00","_phd_date_end":"2025-06-19T16:00:00+00:00","_phd_location":"A\u00f0albygging H\u00e1t\u00ed\u00f0asalur","_phd_admission":"A\u00f0gangur \u00f3keypis","_phd_thesis_title":"\u00c1hrif utangenakerfisins \u00e1 DNA met\u00fdleringu \u00ed tauga\u00feroskam\u00f3deli. 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