Doctoral Defense in Biomedical Sciences - Sara Þöll Halldórsdóttir

On Tuesday, June 24, 2025, Sara Þöll Halldórsdóttir will defend her doctoral dissertation in biomedical sciences at the Faculty of Medicine, University of Iceland. The dissertation is titled: Mechanistic insights into the role of KMT2D in Kabuki syndrome 1.

The opponents are Dr. Giuseppe Merla, Professor at the University of Naples Federico II, Naples, and Siddarth Banka, Professor at the University of Manchester.

The principal advisor and supervisor was Professor Hans Tómas Björnsson. In addition to him, the doctoral committee included Associate Professor Erna Magnúsdóttir, Project Manager Guðmundur L. Norðdahl, Professor Gregg Semenza, and Assistant Professor Jill A. Fahrner.

The ceremony will be chaired by Professor Þórarinn Guðjónsson, Dean of the Faculty of Medicine. It will take place in the Ceremonial Hall (Hátíðasalur) of the University of Iceland and begins at 1:00 PM.

Abstract

Kabuki syndrome type 1 (KS1) is a rare genetic disorder caused by pathogenic variants in the Lysine Methyltransferase 2D (KMT2D). While clinical manifestations vary, individuals with KS1 commonly present with distinctive facial features, intellectual disability, and growth deficiency - reflecting the syndrome’s multi-organ involvement. The main goal of this thesis was to deepen our understanding of KMT2D in disease pathogenesis. This study presents a novel mouse model carrying a patient-specific missense variant which displays core KS features in addition to a novel phenotype of unilateral renal agenesis. In a KMT2D-deficient chondrocyte model, we demonstrate that KMT2D loss impairs mitochondrial metabolism and increases oxidative stress, leading to disrupted chondrocyte differentiation. Notably, we show that this precocious differentiation is reversible by reducing oxidative stress, highlighting a potential mechanistic link between mitochondrial dysfunction and skeletal abnormalities in KS1. CUT&RUN and protein analysis further indicate that KMT2D interacts with the transcription factor E2F4 which is involved in cell cycle regulation and metabolism. These findings highlight a critical role of KMT2D in organ development and particularly in skeletal development via metabolic regulation.

About the Doctoral Candidate

Sara Þöll Halldórsdóttir was born in 1993 in Akureyri. She graduated from the natural sciences track at the Egilsstaðir College in 2013. Sara earned a B.Sc. degree in biomedical science from the University of Iceland in 2016 and a master’s degree, also in biomedical science, in 2018, with a research project at the biotechnology startup Platome.

After graduation, Sara began working as a project manager in the research lab of Dr. Hans Tómas Björnsson and subsequently enrolled in the doctoral program under his supervision in 2020.

Her parents are Elín Sigríður Einarsdóttir and Halldór Jón Halldórsson. Sara’s partner is Friðrik Ingi Þráinsson, and together they have a two-year-old son, Benjamín Þór Friðriksson.