18 April 2023

Thesis defense Maya Wright Clark: Big Data to understand Big Hearts

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On 28 March 2023, Maya Wright Clark successfully defended her thesis “Big Data to understand Big Hearts: Unravelling the molecular mechanisms in hypertrophic cardiomyopathy”. During her PhD in the lab of Eva van Rooij, she used novel sequencing techniques to identify key factors in the onset and progression of the genetic heart disease hypertrophic cardiomyopathy. These factors can in the future potentially be targeted by novel therapies against the disease.

In her thesis, Wright Clark studied the genetic heart disease hypertrophic cardiomyopathy (HCM). The hearts of HCM patients have thickened heart tissue, specifically in the left ventricle. This thickening makes it harder for the heart to pump blood. Nowadays, no treatment exists to cure this common disease, which affects between 1 in 200 and 1 in 500 people. Symptoms can only be alleviated by medication or, in severe cases, surgery.

New approaches

“Surprisingly, the severity of symptoms can vary a lot between patients, even if they are related”, says Wright Clark. In her thesis, she took a unique approach to shed light on these differences. The brand-new doctor explains: “We used two novel sequencing techniques to study the genetic expression of HCM. This allowed us to look at the variation between individual cells as well as their location in the heart. One of these techniques, called single-cell RNA sequencing, had never been performed on human HCM hearts before”.

New therapeutic targets

The approach led to the identification of several genes that were highly expressed in the hypertrophic cells and regions of the heart specifically. In vitro studies on cultured iPSC-derived heart muscle cells showed that one of these genes, the transcription factor NR2F2, is at least partly responsible for the regulation of a group of genes potentially involved in the thickening of the heart muscle. NR2F2 could therefore prove to be a promising target for future therapies against HCM.

Challenges

Despite the results, her PhD was not always easy. “You could say the PhD track is like a rollercoaster with many ups and downs. The pressure of wrapping up several projects in four years can sometimes be overwhelming,” Wright Clark confirms. To handle this stress, she has some advice for future and current PhD students: “It is important that you don’t let setbacks bring you down. Discuss these with colleagues or take some time to clear your mind. It will all come together in the end, I promise!”.

Colleagues

The fact that Wright Clark received an Embryo award, which is presented annually to people who make a special contribution to the institute, shows that she was highly appreciated by her colleagues. Wright Clark assures that this appreciation was mutual: “My colleagues have been of great support whenever I was stuck performing my research. Besides, all the drinks and other social events we had together have made my time at the Hubrecht unforgettable!”.

 

 

Maya had lunch with family and close friends to celebrate her successful defense. After a well-deserved siesta, the celebrations continued with a party. Since she defended her thesis, Maya started working at the biotech company Cergentis.