Our research

At Schurgers Lab, our research is dedicated to advancing the understanding of vascular calcification, vitamin K-dependent proteins, and the role of vitamin K in cardiovascular health. Led by Professor Leon Schurgers, we combine cutting-edge scientific techniques with clinical insights to uncover novel mechanisms and therapeutic approaches.

Our mission is to bridge the gap between fundamental research and practical solutions, addressing key challenges in cardiovascular diseases and aging-related disorders. By collaborating with academic institutions, industry partners, and healthcare professionals, we strive to translate our findings into impactful innovations that improve patient care and public health.

Vascular Remodeling

Vascular remodeling refers to structural changes in arterial blood vessels in response to physiological or pathological stimuli. Its etiology involves multiple mechanisms. The Schurgers’ lab aims to unravel the cellular and molecular patways leading to vascular remodeling:

  1. Cellular Proliferation & Migration – Smooth muscle cell (SMC) proliferation and migration (synthetic SMCs) play a key role in remodeling, especially in diseases like restenosis, aneurysm formation and pulmonary hypertension.

  2. Extracellular Matrix (ECM) Remodeling – Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate ECM degradation and synthesis, influencing vessel structure.

  3. Hemodynamic Forces – Changes in blood flow, shear stress, and pressure can lead to vessel dilation, contraction, or thickening.

  4. Inflammation – Chronic inflammation (e.g., due to hypertension, atherosclerosis, or infection) triggers endothelial dysfunction and smooth muscle proliferation.

  5. Endothelial Dysfunction – Impaired nitric oxide production and oxidative stress contribute to vascular changes.

  6. Genetic & Epigenetic Factors – Variations in genes affecting vascular tone, inflammation, and ECM composition contribute to susceptibility. In here, we are studying monogenetic vascular disorders such as Marfan’s disease, Loeys-Dietz, Ehlers-Danlos, Acta-2, and Myh11.

Vascular remodeling occurs during ageing and conditions such as hypertension, atherosclerosis, aneurysm, chronic kidney disease and diabetic vasculopathy, where it can be either adaptive (maintain function) or maladaptive (leading to vascular disease).

Cardiac Laminopathy

Cardiac laminopathy is a genetic disorder caused by mutations in the LMNA gene, which encodes lamin A and C. These key structural proteins are part of the nuclear envelope. Mutations in the LMNA gene disrupt nuclear integrity, gene regulation, and cellular signaling, and impaired mechanobiology, leading to progressive cardiac dysfunction.

The Schurgers’ lab aims to build a large biobank with biological samples comprising clinical data to investigate:

  1. The genetic basis of LMNA – Autosomal dominant LMNA mutations are the most common, though rare recessive cases exist.

  2. Generate iPSC lines – to conduct fundamental research on patient specific material.

  3. How mutations cause nuclear dysfunction – Mutant lamin proteins cause mechanical instability and impaired gene expression, affecting cardiomyocyte survival.

  4. How this results in inflammation & fibrosis – Chronic cellular stress and apoptosis promote myocardial fibrosis, leading to conduction abnormalities and cardiomyopathy.

  5. Electrophysiological Disruptions – LMNA mutations affect ion channel regulation, increasing the risk of arrhythmias (e.g., atrial fibrillation, ventricular tachycardia).

Clinical Implications: Cardiac laminopathy often presents with dilated cardiomyopathy (DCM), conduction defects, and a high risk of sudden cardiac death (SCD). It is also associated with systemic laminopathies like Emery-Dreifuss muscular dystrophy, Charcot Marie tooth disease and lipodystrophies.

Early diagnosis via genetic testing is crucial for risk stratification and management, including implantable cardioverter-defibrillators (ICDs) to prevent SCD.

Vitamin K and Vitamin K-Dependent Proteins

Vitamin K Overview The biological function of vitamin K is to act as a co-factor for the enzyme 𝛾-glutamyl carboxylase, which adds additional negative charge (in the form of carboxy groups) to the so-called vitamin K-dependent proteins during post-translational modification. The extra negative charge helps the vitamin K-dependent proteins bind calcium ions, thereby enhancing their biological activity. For instance, the coagulation factors II, VII, IX, and X acquire enhanced membrane-binding characteristics, whereas other proteins, such as the MGP, require the additional negative charge to inhibit vascular calcification. More recently, non-canonical roles of vitamin K have been discovered being antioxidant and antiferroptosis. Vitamin K exists in nature in two forms:

  • Phylloquinone (Vitamin K1)

    – Found in green leafy vegetables.

  • Menaquinones (Vitamin K2)

    – Found in fermented foods and produced by the microbiome

The Schurgers group investigates the role of vitamin K and vitamin K-Dependent Proteins (VKDPs):

  1. Coagulation Factors – Essential for blood clotting.

    • Factors II (prothrombin), VII, IX, and X

    • Proteins

      C, S, and Z

      (anticoagulant functions)

  2. Bone and Cartilage Proteins – Important for bone mineralization.

    • Osteocalcin

      – Regulates calcium binding in bones.

    • Matrix Gla Protein (MGP)

      – Prevents arterial calcification.

  3. Vascular and Soft Tissue Proteins – Protect against vascular calcification.

    • Gas6 (Growth Arrest-Specific 6)

      – Involved in cell survival and immune responses.

Vitamin K deficiency can lead to bleeding disorders, osteoporosis, and vascular remodeling and calcification, emphasizing its importance in multiple biological systems.

Within the Schurgers group, we are specialised in vitamin K analysis as well as dp-ucMGP (vascular calcification and vitamin K status), ucOC/cOC (bone turnover and vitamin K status) and PIVKA-II (sub-clinical vitamin K deficiency).

Rett Syndrome

Rett syndrome (RTT) is a rare neurodevelopmental disorder that primarily affects females and is caused by mutations in the MECP2 gene on the X chromosome. This gene encodes methyl-CpG-binding protein 2 (MeCP2), which is crucial for neuronal function and gene regulation.

Aetiology & Pathophysiology

  1. Genetic Basis

    – MECP2 mutations lead to impaired synaptic plasticity and neuronal dysfunction.

  2. Neurodevelopmental Regression

    – Normal early development (first 6–18 months) is followed by loss of acquired motor and communication skills.

  3. Dysautonomia

    – Impaired autonomic nervous system function leads to breathing irregularities, cardiac abnormalities, and gastrointestinal issues.

Clinical Features

  • Loss of purposeful hand use with repetitive hand-wringing movements.

  • Severe speech impairment or complete loss of verbal communication.

  • Motor dysfunction, including ataxia and dystonia.

  • Seizures and cognitive impairment.

  • Autonomic disturbances, such as breathing abnormalities and cardiac dysrhythmias.

At the Schurgers group, we are investigating RETT syndrome by using iPSCs to generate fore-brain organoids, since there is no cure for Rett syndrome. In here, we investigate the transcriptome and proteome of brain organoids to prove a framework for the integration and interpretation of omics data with the aim to find novel pharmacodynamic assessments.