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PhD defence: Signe Mosegaard

Novel insights to fatty acid oxidation disorders - Complex genetics and immunometabolic regulations

2022.01.05 | Graduate School of Health

Date Fri 07 Jan
Time 15:00 17:00
Location Online via Zoom

On Friday 7 January at 15:00, Signe Mosegaard defends her PhD dissertation entitled "Novel insights to fatty acid oxidation disorders - Complex genetics and immunometabolic regulations".

The mitochondrion is the major energy producing and oxygen consuming cellular component and it is important for overall cellular functions. Dysfunction of the mitochondrion may not only affect the cellular energy state but also lead to the release of pro-death factors, increase of reactive oxygen species (ROS) production, and cause a change in metabolic flexibility. Mitochondrial dysfunction with decreased metabolic flexibility is increasingly being recognized as a key element in ageing, cancer, neurodegeneration, diabetes, myocardial dysfunction, and sepsis. Common to all these conditions are also the presence of dysregulated inflammatory responses, and recent years research has revealed that mitochondrial function and inflammatory responses are closely connected. In patients with longchain fatty acid oxidation deficiencies (lcFAOD), mitochondrial dysfunction is a major cellular issue causing decreased metabolic flexibility, and inflammatory events such as infections and exercise are major disease triggers in these disorders.

This PhD project studied two lcFAOD, Multiple Acyl-CoA Dehydrogenation Deficiency (MADD) and Very Long-Chain Acyl-CoA Dehydrogenase Deficiency (VLCADD). In the first study we used whole exome sequencing (WES) combined with transcriptomics and proteomics (diagnostic OMICs) to investigate the genetic complexity and heterogeneity of MADD. In a second study we investigated inflammatory processes in both VLCADD and MADD patient derived fibroblasts and detected that both cellular immune and metabolic responses are different in severe VLCADD and MADD, compared to healthy controls and mild VLCADD. Lastly, we, in a preliminary study, used a mass spectrometry diagnostic tool for lcFAOD, plasma acylcarnitine profiling, as a proxy measure of temporal changes in cellular FAO in a porcine sepsis model.

The summary is written by the PhD student.

The defence is public and takes place online via Zoom. Please read the attached press release for more information.


PhD student Signe Mosegaard

Mail: signe.mosegaard@clin.au.dk

Phone: (+45) 20835507

Read full press release

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