Amsterdam Cardiovascular Sciences

Capillary malformations (CMs), commonly known as port-wine stains, are vascular lesions that affect the skin, eyes and brain. In Sturge-Weber-Syndrome (SWS), these vascular lesions are associated with severe aesthetic, neurological, and ophthalmic complications for patient. While the genetic basis of capillary malformations has become clear, their formation remain poorly understood and patients lack effective treatments. In this project, I will setup high-throughput screening using an innovative imaging-based in vitro model of capillary malformations, aiming to identify evidence-based targeting compounds that restore healthy vascular function.

Cardiovascular disease remains the leading cause of mortality worldwide, driven largely by atherosclerotic plaque instability. While endothelial dysfunction is central to disease progression, current paradigms primarily focus on inflammatory signalling, with limited understanding of how endothelial cell fate is regulated. Emerging evidence suggests that metabolism is not merely a bioenergetic process, but a key determinant of cellular identity.

This project challenges existing dogma by proposing that endothelial metabolic flux actively governs endothelial-to-mesenchymal transition (EndMT), a critical driver of plaque instability. I hypothesize that a shift toward glycolysis and reduced fatty acid oxidation promotes atherogenesis-induced EndMT, while metabolic reprogramming can restore endothelial stability. To test this, I will integrate endothelial-specific genetic models with single-cell and spatial transcriptomics to define metabolic–phenotypic states driving EndMT. Mechanistic studies will determine how metabolic pathways regulate signalling and transcriptional reprogramming, with validation in human atherosclerosis datasets. 

By establishing metabolism as a regulator of endothelial cell fate, this work has the potential to redefine our understanding of vascular disease and uncover fundamentally new therapeutic strategies to stabilize atherosclerotic plaques.

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide, with inflammation playing a causal role. Most evidence on inflammatory risk is derived from predominantly Western populations, potentially overlooking important ethnic differences. This project aims to advance our understanding of inflammatory mechanisms driving ASCVD across diverse populations. Using the multi-ethnic HELIUS cohort in Amsterdam, we will move beyond conventional markers such as high-sensitivity C-reactive protein to perform deep inflammatory profiling with high throughput plasma proteomics. This approach enables the analysis of over 1,000 proteins, allowing detailed characterization of immune pathways involving monocytes, T cells, B cells, and neutrophils. We will identify inflammatory signatures associated with cardiovascular risk and assess how these differ across ethnic groups.

In addition, we will investigate the role of cellular senescence, a key driver of age-related inflammation and a potential major player in perpetuating the chronic inflammatory state in atherosclerotic lesions, by integrating proteomic senescence markers with cardiovascular outcomes. Experimental validation studies will further explore the underlying biological mechanisms.

By combining advanced proteomics with epidemiological and experimental approaches, this project aims to uncover novel inflammatory pathways contributing to ASCVD and improve risk prediction and prevention strategies across diverse populations.