Modelling endothelial cell interactions in pathological lung contexts

Our projects aim to unravel how endothelial cells (ECs) are rewired, and the consequences of this in lung diseases including cystic fibrosis and thoracic lung cancers (non-small cell lung cancer and malignant pleural mesothelioma).
 

In the tumor microenvironment, ECs are primarily recognized for their pro-angiogenic functions, which allow the formation of new blood vessels to irrigate the tumor and ensure metastatic dissemination. ECs are now also been endowed with the ability to tailor immunity, and are considered semi-professional antigen-presenting cells. Consistent with this concept, we previously characterized non-small cell lung cancer (NSCLC) EC heterogeneity using single-cell RNA sequencing (scRNA-seq) and discovered new EC subpopulations with immune regulatory features (Goveia et al., Cancer Cell, 2020).
In the laboratory, we develop several in vitro models to study the alteration of ECs in the tumour microenvironment. These models include secretomes exposition (Bourreau et al., Cancer Med, 2025), complex 2D cocultures, 3D multicellular tumor spheroid MCTS (Krejbich et al., JECCR, 2025), and microfluidic vascularized models. Using the aforementioned models, we follow an integrated approach by combining functional assays, imaging techniques (light-sheet microscopy, 3D confocal imaging), multi-omics and bioinformatic approaches (RNA-seq, scRNA-seq, proteomics).
Patients with cystic fibrosis (pwCF) are experiencing a formidable therapeutic revolution with the era of highly effective modulator therapies, which aim to restore the function of CFTR. The life expectancy of pwCF is now over 60 years, but this is accompanied by an increased prevalence of emerging comorbidities including cardiovascular diseases and a higher risk of cancer. In this context the role of ECs is understudied, but we believe they could play a key role in the pathophysiology, as observed in liver explants from pwCF (Declercq et al., Liver Int, 2024) and in vitro or patient-derived ECs (Declercq et al., ERJ, 2021; Treps et al., J Cyst Fibros, 2021). To better grasp the role of CFTR in ECs, we have developed a genetic mouse model and in vitro models to study ECs differentiated from patient-derived iPSC.

We are currently pursuing two research projects:

• Modeling endothelial cell interactions in the tumor microenvironment with fibroblasts and macrophages

• Studying the role of CFTR in endothelial cells and its role in cystic fibrosis-related emerging comorbidities

In vitro models to mimic tumor endothelial cell-mediated immune cell reprogramming in lung adenocarcinoma. Krejbich M, Navarro E, Fresquet J, Cotinat M, Isen V, Perdrieau H, Forest V, Doméné A, Delaunay T, Awada H, Dochez V, Roulois D, Boisgerault N, Redon R, Blanquart C, Corre I, Treps L#. J Exp Clin Cancer Res. 2025 Nov 27;45(1):15. doi: 10.1186/s13046-025-03576-4

Secretomes From Non-Small Cell Lung Cancer Cells Induce Endothelial Plasticity Through a Partial Endothelial-to-Mesenchymal Transition. Bourreau C, Navarro E, Cotinat M, Krejbich M, Guillonneau F, Guette C, Boissard A, Henry C, Corre I, Treps L, Clere N. Cancer Med. 2025 Mar;14(5):e70707. doi: 10.1002/cam4.70707

Single-cell RNA sequencing of cystic fibrosis liver disease explants reveals endothelial complement activation. Declercq M, Treps L#, Geldhof V, Conchinha NV, de Rooij LPMH, Subramanian A, Feyeux M, Cotinat M, Boeckx B, Vinckier S, Dupont L, Vermeulen F, Boon M, Proesmans M, Libbrecht L, Pirenne J, Monbaliu D, Jochmans I, Dewerchin M, Eelen G, Roskams T, Verleden S, Lambrechts D, Carmeliet P, Witters P. Liver Int. 2024 Sep;44(9):2382-2395. doi: 10.1111/liv.15963. Epub 2024 Jun 7.

Transcriptomic analysis of CFTR-impaired endothelial cells reveals a pro-inflammatory phenotype. Declercq M, de Zeeuw P, Conchinha NV, Geldhof V, Ramalho AS, García-Caballero M, Brepoels K, Ensinck M, Carlon MS, Bird MJ, Vinckier S, Proesmans M, Vermeulen F, Dupont L, Ghesquière B, Dewerchin M, Carmeliet P, Cassiman D, Treps L#, Eelen G#, Witters P#. Eur Respir J. 2021 Apr 22;57(4):2000261. doi: 10.1183/13993003.00261-2020. Print 2021 Apr

An Integrated Gene Expression Landscape Profiling Approach to Identify Lung Tumor Endothelial Cell Heterogeneity and Angiogenic Candidates. Goveia J*, Rohlenova K*, Taverna F*, Treps L*, Conradi LC, Pircher A, Geldhof V, de Rooij LPMH, Kalucka J, Sokol L, García-Caballero M, Zheng Y, Qian J, Teuwen LA, Khan S, Boeckx B, Wauters E, Decaluwé H, De Leyn P, Vansteenkiste J, Weynand B, Sagaert X, Verbeken E, Wolthuis A, Topal B, Everaerts W, Bohnenberger H, Emmert A, Panovska D, De Smet F, Staal FJT, Mclaughlin RJ, Impens F, Lagani V, Vinckier S, Mazzone M, Schoonjans L, Dewerchin M, Eelen G, Karakach TK, Yang H, Wang J, Bolund L, Lin L, Thienpont B, Li X, Lambrechts D, Luo Y, Carmeliet P. Cancer Cell. 2020 Jan 13;37(1):21-36.e13. doi: 10.1016/j.ccell.2019.12.001.
 

Post-doc fellow: Propanna Bandyopadhyay (2025-2026)
PhD students: Morgane Krejbich (2021-2024), Clara Bourreau (2021-2024), Mathias Declercq (2018-2021)
Engineer: Marine Cotinat (2021-2023)
Master students: Emilie Navarro (2024), Morgane Krejbich (2020),
Undergraduate students: Mathis Le Claire (2024), Lylian David (2025), Manon Perchard (2023), Salomé Dupas (2023), Katell Barré (2022), Edith Loisy (2022)