{"id":6421,"date":"2026-10-19T09:48:53","date_gmt":"2026-10-19T09:48:53","guid":{"rendered":"https:\/\/phd.hi.is\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-abbi-elise-smith\/"},"modified":"2026-10-19T09:48:53","modified_gmt":"2026-10-19T09:48:53","slug":"doktorsvorn-i-lif-og-laeknavisindum-abbi-elise-smith","status":"publish","type":"phd_defence","link":"https:\/\/phd.hi.is\/en\/doktorsvorn\/doktorsvorn-i-lif-og-laeknavisindum-abbi-elise-smith\/","title":{"rendered":"Doktorsv\u00f6rn \u00ed l\u00edf- og l\u00e6knav\u00edsindum – Abbi Elise Smith"},"content":{"rendered":"
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F\u00f6studaginn 31. okt\u00f3ber 2025 ver Abbi Elise Smith 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 st\u00f6kkbreytinga \u00ed k\u00f3lester\u00f3lbindiseti Smoothened-pr\u00f3teinsins \u00e1 hedgehog-bo\u00f0ferilinn og slitgigt. The Impact of Smoothened Cholesterol-Binding Pocket Mutations on Hedgehog Signaling and Osteoarthritis.<\/p>\n

Andm\u00e6lendur eru dr. Chrissy Hammond, pr\u00f3fessor vi\u00f0 University of Bristol, Englandi, og dr. Melanie Philipp, pr\u00f3fessor vi\u00f0 Eberhard-Karls-Universit\u00e4t \u00ed T\u00fcbingen, \u00de\u00fdskalandi.\u00a0<\/p>\n

Umsj\u00f3narkennari var Eir\u00edkur Steingr\u00edmsson og lei\u00f0beinandi Sara Sigurbj\u00f6rnsd\u00f3ttir. Auk \u00feeirra s\u00e1tu \u00ed doktorsnefnd Bj\u00f6rn Gu\u00f0bj\u00f6rnsson, pr\u00f3fessor, Karl \u00c6gir Karlsson, pr\u00f3fessor, \u00d3lafur Eysteinn Sigurj\u00f3nsson, pr\u00f3fessor og Unnur Styrk\u00e1rsd\u00f3ttir, v\u00edsindama\u00f0ur.<\/p>\n

S\u00e6d\u00eds S\u00e6varsd\u00f3ttir, pr\u00f3fessor og deildarforseti L\u00e6knadeildar, 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

Hedgehog-bo\u00f0ferillinn gegnir lykilhlutverki \u00ed f\u00f3stur\u00feroskun, einkum fyrir \u00feroskun \u00fatlima, h\u00f6fu\u00f0k\u00fapu og beinv\u00f6xt. \u00d3e\u00f0lileg virkjun bo\u00f0ferilsins seinna \u00e1 l\u00edfslei\u00f0inni getur hins vegar stu\u00f0la\u00f0 a\u00f0 \u00fer\u00f3un slitgigtar. St\u00f6kkbreytingin p.Arg173Cys; SMOR173C \u00ed Smoothened (SMO) geninu, sem er hluti af hedgehog-bo\u00f0lei\u00f0inni, hefur veri\u00f0 tengd aukinni h\u00e6ttu \u00e1 slitgigt \u00ed mj\u00f6\u00f0m (SMOR173C). Breytingin hefur veri\u00f0 talin hafa \u00e1hrif \u00e1 bindingu SMO vi\u00f0 k\u00f3lester\u00f3l.<\/p>\n

\u00cd verkefninu voru \u00fer\u00edv\u00ed\u00f0ar r\u00e6ktanir \u00e1 ATDC5 brj\u00f3skmyndandi m\u00fasafrumum nota\u00f0ar \u00e1samt greiningu \u00e1 svipger\u00f0 sebrafiskaf\u00f3stra til a\u00f0 s\u00fdna a\u00f0 SMOR173C afbrig\u00f0i\u00f0 raska\u00f0i ekki hedgehog-bo\u00f0lei\u00f0inni og hefur ekki \u00e1hrif \u00e1 bindingu k\u00f3lester\u00f3ls. Hins vegar hefur SMOR173C st\u00f6kkbreytingin \u00e1hrif \u00e1 tj\u00e1ningu\u00a0 Mmp13, ens\u00edms sem ber \u00e1byrg\u00f0 \u00e1 ni\u00f0urbroti brj\u00f3sks. \u00deetta \u00f3v\u00e6nta samband milli hedgehog-bo\u00f0lei\u00f0arinnar og tj\u00e1ningar MMP13 er hugsanleg sk\u00fdring \u00e1 tengingu vi\u00f0 slitgigt og m\u00f6guleg lei\u00f0 til me\u00f0fer\u00f0ar.<\/p>\n

\u00der\u00f3unarfr\u00e6\u00f0ilegar greiningar \u00e1 erf\u00f0amengi geislaugga (beinfiska) s\u00fdndu a\u00f0 smo geni\u00f0 hefur var\u00f0veist \u00ed einu eintaki \u00ed gegnum \u00fer\u00f3unars\u00f6guna. V\u00edsbendingar fundust um a\u00f0 st\u00f6kkbreytingar \u00ed smo tengist frekar \u00e6ttum sem hafa fj\u00f6lbreytt l\u00edkamsform, svo sem lengri l\u00edkama og breytingar \u00e1 h\u00f6fu\u00f0lagi. \u00de\u00e1 kom einnig \u00ed lj\u00f3s a\u00f0 arfblendin smo sebrafiskaf\u00f3stur h\u00f6f\u00f0u \u00f3e\u00f0lilega frumli\u00f0a- og kj\u00e1lkager\u00f0 og sem fullor\u00f0nir fiskar s\u00fdndu \u00feeir aukningu \u00e1 galla \u00ed beinum. \u00deessar ni\u00f0urst\u00f6\u00f0ur endurspegla n\u00e6mni fyrir genamagnsbreytingum \u00ed smo \u00ed \u00fer\u00f3unars\u00f6gu geislaugga.<\/p>\n

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

The hedgehog signaling pathway plays a vital role in development, and is particularly important for limb patterning, somitogenesis, craniofacial development, and bone growth. When aberrantly activated later in life, elevated hedgehog signaling contributes to the development of osteoarthritis and is associated with worsened cartilage phenotype. A deCODE genetics GWAS study identified a variant in the hedgehog pathway gene Smoothened (SMO) that is associated with increased risk of hip osteoarthritis (SMOR173C). The variant was hypothesized to alter the binding of cholesterol to SMO, affecting downstream HH signaling.<\/p>\n

We used 3D hydrogel culture of ATDC5 cells and analysis of phenotypic recovery in smo-deficient zebrafish embryos microinjected with human SMO mRNA to show that the SMOR173C variant did not disrupt downstream hedgehog signaling. Furthermore, we found that the SMOR173C variant in ATDC5 cells showed elevated Mmp13 expression, an enzyme responsible for cartilage degradation. This study lays the groundwork to identify a direct link between the hedgehog signaling pathway and MMP13 expression.<\/p>\n

Finally, we used evolutionary analysis of teleost (bony fish) genomes to determine that the smo gene has been retained as a single copy throughout evolutionary history, and that smo mutations are present in lineages that exhibit body plan diversification such as body elongation and head shape. We determined that heterozygous smo zebrafish had altered somite and jaw development in embryogenesis, and increased incidence of skeletal malformations as adults, compared to their homozygous wildtype smo siblings. These data reflect a gene dose sensitivity of smo in teleost evolutionary history.<\/p>\n

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

Abbi Elise Smith f\u00e6ddist \u00ed Wooster \u00ed Ohio-fylki \u00ed Bandar\u00edkjunum \u00e1ri\u00f0 1984. H\u00fan lauk BS pr\u00f3fi \u00ed d\u00fdrafr\u00e6\u00f0i fr\u00e1 Ohio State h\u00e1sk\u00f3lanum \u00e1ri\u00f0 2007 og MS gr\u00e1\u00f0u \u00ed l\u00edffr\u00e6\u00f0i fr\u00e1 H\u00e1sk\u00f3lanum \u00ed Maryland \u00e1ri\u00f0 2011. H\u00fan kenndi s\u00ed\u00f0an l\u00edffr\u00e6\u00f0i og l\u00edff\u00e6rafr\u00e6\u00f0i vi\u00f0 Ivy Tech Community College \u00ed Bloomington \u00ed Indiana en \u00e1rin 2015-2021 vann h\u00fan \u00e1 ranns\u00f3knastofu vi\u00f0 l\u00e6knadeild h\u00e1sk\u00f3lans \u00ed Indiana. \u00c1ri\u00f0 2021 h\u00f3f h\u00fan doktorsn\u00e1m vi\u00f0 H\u00e1sk\u00f3la \u00cdslands \u00fear sem h\u00fan vann ranns\u00f3knaverkefni undir lei\u00f0s\u00f6gn S\u00f6ru Sigurbj\u00f6rnsd\u00f3ttur. Abbi hefur teki\u00f0 \u00fe\u00e1tt \u00ed lei\u00f0beiningu nema og verklegri kennslu vi\u00f0 H\u00cd en auk \u00feess var h\u00fan fulltr\u00fai doktorsnema \u00ed stj\u00f3rn L\u00edfv\u00edsindaseturs.<\/p>\n<\/div><\/div>","protected":false},"featured_media":5808,"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":"2025-10-31T13:00:00+00:00","_phd_date_end":"2025-10-31T16:00:00+00:00","_phd_location":"A\u00f0albygging H\u00e1t\u00ed\u00f0asalur","_phd_admission":"A\u00f0gangur \u00f3keypis","_phd_thesis_title":"\u00c1hrif st\u00f6kkbreytinga \u00ed k\u00f3lester\u00f3lbindiseti Smoothened-pr\u00f3teinsins \u00e1 hedgehog-bo\u00f0ferilinn og slitgigt. 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