Laura de Rooij

Endothelial cells line the interior surface of all blood vessels and are essential for the regulation of vascular tone, blood vessel growth, inflammation, permeability, and coagulation. Throughout the body’s organs and tissues, the endothelium shows a remarkable degree of structural, phenotypic, and functional heterogeneity. Moreover, endothelial cell dysfunction is a major driver of morbidity and mortality across a wide range of diseases, underscoring the systemic importance of this dynamic cell population.

The de Rooij lab aims to combine single-cell omics and functional vascular assays to increase our fundamental understanding of endothelial cell heterogeneity and its role in vascular aging and pathology. Our overarching goal is to explore the translational relevance of endothelial cells and their tissue-, aging-, and disease-specific phenotypes for the diagnosis and treatment of vascular pathologies. 

Characterizing endothelial cells one cell at a time

The single-cell era has led to the emergence of a multitude of studies and technologies that have revolutionized our understanding of cellular heterogeneity from both physiological and pathophysiological perspectives. Recent single-cell omics studies have revealed that endothelial cells are transcriptomically heterogeneous, encompassing multiple subtypes with distinct gene expression profiles depending on tissue of origin or disease context. From an aging perspective, however, the degree and role of endothelial heterogeneity remain poorly understood. Moreover, endothelial rewiring remains an early yet often overlooked aspect of human disease progression. 

We thus aim to obtain a high-resolution view of the endothelium in different organs, tissues, and conditions, by leveraging single-cell technologies. Key questions driving our research include: Do all endothelial cells age the same way, regardless of the organ/tissue they reside in? Does pathology or aging affect the ability of the endothelium to effectively expand or repair itself? And can we find better ways to detect, prevent, and delay disease-associated rewiring of our endothelium in a tissue-specific manner?  

In vitro modeling of the human endothelium

Our high-resolution omics approaches allow us to chart vascular niches in both healthy and diseased contexts and to discover novel genes and pathways involved in endothelial function, pathology, and aging. To explore the functional roles of these discoveries, we employ a broad toolkit of in vitro models to study and perturb organotypically diverse endothelial cells in healthy or disease-mimicking setups. These models are further enhanced using 3D culture platforms including vessel-on-chip systems, which allow us to recapitulate tissue-specific signals such as extracellular matrix composition and co-culture with relevant non-vascular cell types. 

Our research addresses key questions such as: How do aging and cellular senescence impair the function and angiogenic capacity of endothelial cells? And how can we further improve in vitro vascular culture systems to better recapitulate the complexity of the human endothelium across different organs and tissues?

Laura de Rooij studied biomedical sciences at the University of Amsterdam (The Netherlands). She then joined the Stem Cell and Cancer Research Institute at McMaster University in Hamilton (Canada), where she studied the role of RNA-binding proteins in leukemic stem cells via an in vivo two-step CRISPR-Cas9-mediated screening approach. For her postdoctoral studies, she returned to Europe to work under the mentorship of Professor Carmeliet in the lab of Angiogenesis and Vascular Metabolism at VIB-KU Leuven (Belgium). There, she led and contributed to numerous single-cell transcriptome atlases of endothelial cells, generated from a diverse range of tissues, preclinical models, and clinical patient material in health and disease. Her studies have shed new light on the degree of vessel subtype heterogeneity in different tissues, as well as the altered composition and rewired molecular circuitries of endothelial cell subtypes in disease. Moreover, her efforts led to the discovery of previously unknown vascular subtypes and functions, including endothelial cells with a lipid-processing phenotype and potential prognostic relevance in breast cancer and endothelial cells with a putative profibrotic function in COVID-19. Laura de Rooij joined CeMM as principal investigator in September 2022. Her lab focuses on deciphering the transcriptomic landscape and the role of circulating endothelial cells in health and aging.

Dobner, S., Tóth, F. & de Rooij, L.P.M.H. A high-resolution view of the heterogeneous aging endothelium. Angiogenesis. 2024 May;27(2):129-145. (abstract)

de Rooij, L.P.M.H.*, Becker, L.M.* et al. The pulmonary vasculature in lethal COVID-19 and idiopathic pulmonary fibrosis at single cell resolution. Cardiovasc Res. 2022 Aug 23:cvac139. doi: 10.1093/cvr/cvac139. (abstract)

Geldhof V, et al. Single cell atlas identifies lipid-processing and immunomodulatory endothelial cells in healthy and malignant breast. Nat Commun. 2022 Sep 20;13(1):5511. (abstract)

de Rooij, L.P.M.H., Becker, L.M. & Carmeliet, P. A role for the vascular endothelium in post-acute COVID-19? Circulation. 2022 May 17;145(20):1503-1505. (abstract)

Becker, L.M.*, Chen, S.H.*, Rodor, J.*, de Rooij, L.P.M.H.* et al. Deciphering endothelial heterogeneity in health and disease at single cell resolution: progress and perspectives. Cardiovasc Res. 2022 Feb 18:cvac018. (abstract) 

Vujovic, A.*, de Rooij, L.P.M.H.* et al. In Vivo Screening Unveils Pervasive RNA-Binding Protein Dependencies in Leukemic Stem Cells and Identifies ELAVL1 as a Therapeutic Target. Blood Cancer Discovery. 2023, 4 (3): 180–207. (abstract)

Teuwen, L.A., de Rooij, L.P.M.H. et al. Tumor vessel co-option probed by single-cell analysis. Cell Rep. 2021 Jun 15;35(11):109253. (abstract)

Kalucka, J.*, de Rooij, L.P.M.H.*, Goveia, J.* et al. A single cell transcriptome atlas of murine endothelial cells. Cell. 2020 Feb 20;180(4):764-779.e20. (abstract)

Goveia, J. et al. An Integrated Gene Expression Landscape Profiling Approach to Identify Lung Tumor Endothelial Cell Heterogeneity and Angiogenic Candidates. Cancer Cell. 2020 Jan 13;37(1):21-36.e13. Erratum in: Cancer Cell. 2020 Mar 16;37(3):421. (abstract)

*joint first authorship