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About Our Reseach Focus
The Stellos Lab is located at the European Center for Angioscience of the Heidelberg University in Mannheim, Germany. Our research focuses on the regulatory role of RNA in vascular endothelial control of age- and metabolic dysfunction-related diseases. Specifically, we investigate how inflammatory, metabolic, and RNA-biological mechanisms drive vascular and multi-organ disease.
The accompanying figure illustrates how ageing, hypertension, dyslipidemia, obesity, Western diet, and (epi)genetic risk converge on endothelial inflammation and dysregulation of RNA editing and modification. These processes promote cardiometabolic, renal, pulmonary, oncologic, and neurodegenerative diseases. Our mission is to translate these mechanisms into improved diagnostics and therapeutic strategies for patients.
1. RNA in Systems Biology and Medicine
Our research investigates how RNA editing and epitranscriptomic modifications function as dynamic regulatory layers that shape endothelial behavior, modulate immune cell activation, and drive vascular remodeling across cardiometabolic, inflammatory, and age-associated diseases. Building on the lab’s strong foundation in cardiovascular RNA biology, we combine multi-omics profiling of deeply phenotyped patient cohorts with mechanistic studies in human endothelial, hematopoietic, and immune cell systems. This integrated systems-level strategy allows us to map disease-associated RNA editing signatures, RNA modification patterns, and non-coding RNA networks that govern transcriptional plasticity, intercellular communication, and vascular homeostasis.
Using state-of-the-art technologies—including long-read RNA sequencing, direct RNA modification mapping, high-resolution imaging, and perturbation-based functional genomics—we identify RNA-driven signatures linked to disease progression, inflammatory activation, and therapeutic response. A particular focus is placed on uncovering causal RNA regulators, such as ADAR-mediated editing events, m⁶A-dependent control of transcript fate, and RNA–protein interactions that orchestrate cellular adaptation to metabolic and inflammatory stress.
By bridging fundamental mechanistic insights with clinically grounded research questions, our lab aims to transform RNA biology into actionable biomarkers, predictive tools, and innovative RNA-targeted therapeutic strategies. Ultimately, our work advances a precision RNA medicine framework with the potential to reshape the prevention, diagnosis, and treatment of vascular and inflammatory disorders.
Selected publications
1: Vlachogiannis NI, Polycarpou-Schwarz M, Avdi AP, Tual-Chalot S, Stellos K.Targeting RNA adenosine editing and modification enzymes for RNA therapeutics. Mol Ther. 2025 Sep 3;33(9):4044-4090. doi: 10.1016/j.ymthe.2025.05.021.
2: Sachse M, Stellos K. Unraveling the RNA code: a uridine RNA modification drives glycoRNA biogenesis. Signal Transduct Target Ther. 2024 Nov 27;9(1):334. doi: 10.1038/s41392-024-02056-z.
3: Gatsiou A, Tual-Chalot S, Napoli M, Ortega-Gomez A, Regen T, Badolia R, Cesarini V, Garcia-Gonzalez C, Chevre R, Ciliberti G, Silvestre-Roig C, Martini M, Hoffmann J, Hamouche R, Visker JR, Diakos N, Wietelmann A, Silvestris DA, Georgiopoulos G, Moshfegh A, Schneider A, Chen W, Guenther S, Backs J, Kwak S, Selzman CH, Stamatelopoulos K, Rose-John S, Trautwein C, Spyridopoulos I, Braun T, Waisman A, Gallo A, Drakos SG, Dimmeler S, Sperandio M, Soehnlein O, Stellos K. The RNA editor ADAR2 promotes immune cell trafficking by enhancing endothelial responses to interleukin-6 during sterile inflammation. Immunity. 2023 May 9;56(5):979-997.e11. doi: 10.1016/j.immuni.2023.03.021.
4: Sachse M, Tual-Chalot S, Ciliberti G, Amponsah-Offeh M, Stamatelopoulos K, Gatsiou A, Stellos K. RNA-binding proteins in vascular inflammation and atherosclerosis. Atherosclerosis. 2023 Jun;374:55-73. doi: 10.1016/j.atherosclerosis.2023.01.008.
5: Gatsiou A, Stellos K. RNA modifications in cardiovascular health and disease. Nat Rev Cardiol. 2023 May;20(5):325-346. doi: 10.1038/s41569-022-00804-8.
6: Vlachogiannis NI, Tual-Chalot S, Zormpas E, Bonini F, Ntouros PA, Pappa M, Bournia VK, Tektonidou MG, Souliotis VL, Mavragani CP, Stamatelopoulos K, Gatsiou A, Sfikakis PP, Stellos K. Adenosine-to-inosine RNA editing contributes to type I interferon responses in systemic sclerosis. J Autoimmun. 2021 Dec;125:102755. doi: 10.1016/j.jaut.2021.102755.
7: Vlachogiannis NI, Sachse M, Georgiopoulos G, Zormpas E, Bampatsias D, Delialis D, Bonini F, Galyfos G, Sigala F, Stamatelopoulos K, Gatsiou A, Stellos K. Adenosine-to-inosine Alu RNA editing controls the stability of the pro-inflammatory long noncoding RNA NEAT1 in atherosclerotic cardiovascular disease. J Mol Cell Cardiol. 2021 Nov;160:111-120. doi: 10.1016/j.yjmcc.2021.07.005.
8: Stellos K, Gatsiou A, Stamatelopoulos K, Perisic Matic L, John D, Lunella FF, Jaé N, Rossbach O, Amrhein C, Sigala F, Boon RA, Fürtig B, Manavski Y, You X, Uchida S, Keller T, Boeckel JN, Franco-Cereceda A, Maegdefessel L, Chen W, Schwalbe H, Bindereif A, Eriksson P, Hedin U, Zeiher AM, Dimmeler S. Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation. Nat Med. 2016 Oct;22(10):1140-1150. doi: 10.1038/nm.4172. Epub 2016 Sep 5. PMID: 27595325.
2. Understanding how metabolism shapes vascular health
Our lab focuses on understanding how metabolic dysfunction—particularly in diabetes and obesity—drives vascular inflammation and contributes to persistent cardiovascular risk despite standard therapy. Through the Angiometabolic Study, a prospective cross-European cohort, we combine structured clinical workflows, advanced vascular imaging, and molecular profiling to generate insights that directly inform risk stratification and patient management.
Integrated Clinical Workflow
Participants undergo standardized, reproducible assessments at baseline and follow-up visits, including:
- Comprehensive clinical phenotyping and cardiometabolic risk scoring
- Biomarker-based profiling (inflammatory markers, metabolic indices)
- Longitudinal follow-up for atherosclerosis progression and major cardiovascular outcomes
- This protocol enables consistent evaluation across centers and facilitates real-world clinical translation.
Advanced Vascular Imaging
We employ a multimodal vascular imaging pipeline designed to capture disease across the arterial tree:
- High-resolution ultrasound for carotid, aorta and femoral atherosclerosis burden and plaque progression
- Pulse-wave velocity (PWV) for assessment of macrovascular stiffness
- Microvascular reactivity testing for early endothelial dysfunction
- Ambulatory and central aortic blood pressure monitoring for hemodynamic characterization
These imaging modalities provide clinicians with actionable markers of vascular health and early disease progression.
Clinical Relevance and Patient Benefit
Our integrated approach supports clinicians by:
- Identifying individuals at high residual cardiovascular risk despite guideline-directed therapy
- Detecting subclinical vascular disease before symptomatic presentation
- Improving risk prediction using combined imaging and biomarker signatures
- Enabling more personalized treatment decisions, including timing of pharmacotherapy escalation
- Informing follow-up intensity and preventive strategies
By linking mechanistic insights with real-world clinical endpoints, we aim to enhance early detection, refine patient stratification, and support precision vascular care across the cardiometabolic spectrum.
Selected publications
1: Mavraganis G, Georgiopoulos G, Athanasopoulos S, Terentes-Printzios D, Zervas G, Konstantaki C, Koilakou ME, Giannakopoulou SP, Dimopoulou MA, Chrysochoou C, Tsioufis K, Pitsavos C, Liberopoulos E, Stellos K, Vlachopoulos C, Panagiotakos D, Stamatelopoulos K. Improving cardiovascular risk stratification through the derivation and validation of an elevated triglyceride-glucose index. Diabetes Obes Metab. 2025 Nov 3. doi: 10.1111/dom.70270. Epub ahead of print. PMID: 41178693.
2: Mastrangelo A, Robles-Vera I, Mañanes D, Galán M, Femenía-Muiña M, Redondo-Urzainqui A, Barrero-Rodríguez R, Papaioannou E, Amores-Iniesta J, Devesa A, Lobo-González M, Carreras A, Beck KR, Ivarsson S, Gummesson A, Georgiopoulos G, Rodrigo-Tapias M, Martínez-Cano S, Fernández-López I, Nuñez V, Ferrarini A, Inohara N, Stamatelopoulos K, Benguría A, Cibrian D, Sánchez-Madrid F, Alonso-Herranz V, Dopazo A, Barbas C, Vázquez J, López JA, González-Martín A, Nuñez G, Stellos K, Bergström G, Bäckhed F, Fuster V, Ibañez B, Sancho D. Imidazole propionate is a driver and therapeutic target in atherosclerosis. Nature. 2025 Sep;645(8079):254-261. doi: 10.1038/s41586-025-09263-w. Epub 2025 Jul 16. PMID: 40670786; PMCID: PMC12408353.
3: Mavraganis G, Georgiopoulos G, Zervas G, Aivalioti E, Delialis D, Petropoulos I, Rachiotis N, Konstantaki C, Moustou C, Dimopoulou MA, Sachse M, Tual-Chalot S, Sopova K, Psimmenou E, Stellos K, Stamatelopoulos K. Circulating amyloid beta 1-40 peptide as an associate of renal function decline. Eur J Clin Invest. 2025 May;55(5):e70006. doi: 10.1111/eci.70006. Epub 2025 Feb 24. PMID: 39989380; PMCID: PMC12011680.
4: Georgiopoulos G, Athanasopoulos S, Mavraganis G, Konstantaki C, Papaioannou M, Delialis D, Angelidakis L, Sachse M, Papoutsis D, Cavlan B, Tual-Chalot S, Zervas G, Sopova K, Mitrakou A, Stellos K, Stamatelopoulos K. Incremental Value of Blood-Based Markers of Liver Fibrosis in Cardiovascular Risk Stratification. J Clin Endocrinol Metab. 2025 Mar 17;110(4):1115-1127. doi: 10.1210/clinem/dgae619. PMID: 39257198; PMCID: PMC11913098.
3. ImmunoVascular Control of Health and Disease
Dysregulated communication between endothelial and immune cells is one of the main drivers of vascular ageing, atherosclerosis, ischemic injury, and chronic inflammation. The Stellos Lab focuses on deciphering the mechanisms that govern immune-vascular interactions, beyond the major inflammatory pathways. Our recent work has uncovered key RNA-based regulators of endothelial activation, including the ADAR2-dependent RNA editing pathways that modulate leukocyte recruitment. Building on these findings, we now aim to integrate multi-omics profiling, computational modelling, and functional vascular biology to identify novel RNA-centered targets that can be therapeutically leveraged to restore immune-vascular homeostasis and prevent cardiovascular disease progression.
Selected publications
1: Gatsiou A, Tual-Chalot S, Napoli M, Ortega-Gomez A, Regen T, Badolia R, Cesarini V, Garcia-Gonzalez C, Chevre R, Ciliberti G, Silvestre-Roig C, Martini M, Hoffmann J, Hamouche R, Visker JR, Diakos N, Wietelmann A, Silvestris DA, Georgiopoulos G, Moshfegh A, Schneider A, Chen W, Guenther S, Backs J, Kwak S, Selzman CH, Stamatelopoulos K, Rose-John S, Trautwein C, Spyridopoulos I, Braun T, Waisman A, Gallo A, Drakos SG, Dimmeler S, Sperandio M, Soehnlein O, Stellos K. The RNA editor ADAR2 promotes immune cell trafficking by enhancing endothelial responses to interleukin-6 during sterile inflammation. Immunity. 2023 May 9;56(5):979-997.e11. doi: 10.1016/j.immuni.2023.03.021. Epub 2023 Apr 25. PMID: 37100060.
2: Maneta E, Aivalioti E, Tual-Chalot S, Emini Veseli B, Gatsiou A, Stamatelopoulos K, Stellos K. Endothelial dysfunction and immunothrombosis in sepsis. Front Immunol. 2023 Apr 4;14:1144229. doi: 10.3389/fimmu.2023.1144229. PMID: 37081895; PMCID: PMC10110956.
3: Sachse M, Tual-Chalot S, Ciliberti G, Amponsah-Offeh M, Stamatelopoulos K, Gatsiou A, Stellos K. RNA-binding proteins in vascular inflammation and atherosclerosis. Atherosclerosis. 2023 Jun;374:55-73. doi: 10.1016/j.atherosclerosis.2023.01.008. Epub 2023 Jan 17. PMID: 36759270.
4: Vlachogiannis NI, Sachse M, Georgiopoulos G, Zormpas E, Bampatsias D, Delialis D, Bonini F, Galyfos G, Sigala F, Stamatelopoulos K, Gatsiou A, Stellos K. Adenosine-to-inosine Alu RNA editing controls the stability of the pro-inflammatory long noncoding RNA NEAT1 in atherosclerotic cardiovascular disease. J Mol Cell Cardiol. 2021 Nov;160:111-120. doi: 10.1016/j.yjmcc.2021.07.005. Epub 2021 Jul 21. PMID: 34302813; PMCID: PMC8585018.
5: Stellos K, Gatsiou A, Stamatelopoulos K, Perisic Matic L, John D, Lunella FF, Jaé N, Rossbach O, Amrhein C, Sigala F, Boon RA, Fürtig B, Manavski Y, You X, Uchida S, Keller T, Boeckel JN, Franco-Cereceda A, Maegdefessel L, Chen W, Schwalbe H, Bindereif A, Eriksson P, Hedin U, Zeiher AM, Dimmeler S. Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation. Nat Med. 2016 Oct;22(10):1140-1150. doi: 10.1038/nm.4172. Epub 2016 Sep 5. PMID: 27595325.
4. Cardiovascular Ageing & Systemic Disease
Cardiovascular ageing is a systems-level process in which vascular homeostasis progressively declines, increasing vulnerability to heart failure, kidney disease, pulmonary vascular disorders, cancer progression, and dementia. Our research programme approaches this complex biology through an integrated framework that connects vascular ageing, immune–vascular crosstalk, and protein misfolding.
A central focus of our work is amyloid-β40, traditionally viewed as a neurocentric molecule. We reposition Aβ40 as a potent vascular stressor that drives endothelial dysfunction, inflammation, atherogenesis, and arterial stiffening—reframing aspects of arterial ageing as a protein-misfolding disease.
In parallel, we investigate how ageing reshapes the metabolic and functional states of immune and stromal cells, activates transposable elements and cGAS–STING signalling, and remodels the epigenetic and epitranscriptomic landscape, pushing tissues into persistent inflammatory states.
To capture this multidimensional biology, we combine single-cell and spatial multi-omics, comparative analyses in long-lived species, engineered mouse models, and deeply phenotyped human ageing cohorts. Our goal is to translate these insights into minimally invasive biomarkers—including Aβ40—and into senotherapeutic, metabolic, anti-LINE1, and multimodal interventions that restore immune–vascular balance and slow vascular decline.
Selected publications
1: Liberale L, Tual-Chalot S, Sedej S, Ministrini S, Georgiopoulos G, Grunewald M, Bäck M, Bochaton-Piallat ML, Boon RA, Ramos GC, de Winther MPJ, Drosatos K, Evans PC, Ferguson JF, Forslund-Startceva SK, Goettsch C, Giacca M, Haendeler J, Kallikourdis M, Ketelhuth DFJ, Koenen RR, Lacolley P, Lutgens E, Maffia P, Miwa S, Monaco C, Montecucco F, Norata GD, Osto E, Richardson GD, Riksen NP, Soehnlein O, Spyridopoulos I, Van Linthout S, Vilahur G, Wentzel JJ, Andrés V, Badimon L, Benetos A, Binder CJ, Brandes RP, Crea F, Furman D, Gorbunova V, Guzik TJ, Hill JA, Lüscher TF, Mittelbrunn M, Nencioni A, Netea MG, Passos JF, Stamatelopoulos KS, Tavernarakis N, Ungvari Z, Wu JC, Kirkland JL, Camici GG, Dimmeler S, Kroemer G, Abdellatif M, Stellos K. Roadmap for alleviating the manifestations of ageing in the cardiovascular system. Nat Rev Cardiol. 2025 Aug;22(8):577-605. doi: 10.1038/s41569-025-01130-5. Epub 2025 Feb 19. PMID: 39972009.
2: Aivalioti E, Georgiopoulos G, Tual-Chalot S, Bampatsias D, Delialis D, Sopova K, Drakos SG, Stellos K, Stamatelopoulos K. Amyloid-beta metabolism in age-related neurocardiovascular diseases. Eur Heart J. 2025 Jan 16;46(3):250-272. doi: 10.1093/eurheartj/ehae655. PMID: 39527015; PMCID: PMC11735085.
3: Stakos DA, Stamatelopoulos K, Bampatsias D, Sachse M, Zormpas E, Vlachogiannis NI, Tual-Chalot S, Stellos K. The Alzheimer's Disease Amyloid-Beta Hypothesis in Cardiovascular Aging and Disease: JACC Focus Seminar. J Am Coll Cardiol. 2020 Mar 3;75(8):952-967. doi: 10.1016/j.jacc.2019.12.033. PMID: 32130931; PMCID: PMC7042886.
3: Delialis D, Georgiopoulos G, Tual-Chalot S, Angelidakis L, Aivalioti E, Mavraganis G, Sopova K, Argyris A, Kostakou P, Konstantaki C, Papaioannou M, Tsilimigras D, Chatoupis K, Zacharoulis AA, Galyfos G, Sigala F, Stellos K, Stamatelopoulos K. Amyloid beta is associated with carotid wall echolucency and atherosclerotic plaque composition. Sci Rep. 2024 Jun 28;14(1):14944. doi: 10.1038/s41598-024-64906-8. PMID: 38942831; PMCID: PMC11213915.
4: Stamatelopoulos K, Pol CJ, Ayers C, Georgiopoulos G, Gatsiou A, Brilakis ES, Khera A, Drosatos K, de Lemos JA, Stellos K. Amyloid-Beta (1-40) Peptide and Subclinical Cardiovascular Disease. J Am Coll Cardiol. 2018 Aug 28;72(9):1060-1061. doi: 10.1016/j.jacc.2018.06.027. PMID: 30139434; PMCID: PMC6467498.
5: Stamatelopoulos K, Mueller-Hennessen M, Georgiopoulos G, Sachse M, Boeddinghaus J, Sopova K, Gatsiou A, Amrhein C, Biener M, Vafaie M, Athanasouli F, Stakos D, Pateras K, Twerenbold R, Badertscher P, Nestelberger T, Dimmeler S, Katus HA, Zeiher AM, Mueller C, Giannitsis E, Stellos K. Amyloid-β (1-40) and Mortality in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome: A Cohort Study. Ann Intern Med. 2018 Jun 19;168(12):855-865. doi: 10.7326/M17-1540. Epub 2018 May 22. PMID: 29799975.
6: Stamatelopoulos K, Sibbing D, Rallidis LS, Georgiopoulos G, Stakos D, Braun S, Gatsiou A, Sopova K, Kotakos C, Varounis C, Tellis CC, Kastritis E, Alevizaki M, Tselepis AD, Alexopoulos P, Laske C, Keller T, Kastrati A, Dimmeler S, Zeiher AM, Stellos K. Amyloid-beta (1-40) and the risk of death from cardiovascular causes in patients with coronary heart disease. J Am Coll Cardiol. 2015 Mar 10;65(9):904-16. doi: 10.1016/j.jacc.2014.12.035. PMID: 25744007.