SANTOVITO LAB
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The translational vascular therapy research group studies the role of epigenetics and autophagy in atherosclerosis and cardiovascular disease.
- In particular, the research focuses on understanding the molecular mechanisms behind canonical and noncanonical features of microRNA function and trafficking, the interaction of multiple epigenetic regulatory mechanisms, and how they contribute to communication between stromal and immune cells within and beyond the vessel wall.
- The goal is to identify molecular mechanisms that can be exploited as therapeutic targets or diagnostic/prognostic markers to improve the standard of care for atherosclerosis and cardiovascular diseases.
LATEST NEWS FROM THE LAB
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- Non-canonical functional paradigms of microRNAs.
Synopsis of the miRNA-disengagement approach: Some MIRNA genes are located in the proximity of cell type-specific enhancers/superenhancers. Target site blocker (TSB) oligonucleotides preventing the interaction of cell-specific miRNAs with ubiquitously expressed transcripts offer the opportunity for cell-specific gene enhancement. By this approach, a TSB averting miR-206 from repressing CXCR4 in the cells of the vessel wall (i.e., endothelial and smooth muscle cells) to promote antiatherogenic features, without off-target effects in myeloid cells that do not express miR-206.
- Epigenetic mechanisms in vascular biology.
The transcriptional landscape of every cell is shaped by multiple layers of epigenetic control. They range from the regulation of chromatin accessibility by DNA methylation and histone modifications to post-transcriptional repression of RNA transcripts by microRNAs. These epigenetic mechanisms often act in concert and are regulated in homeostasis and disease conditions within cells of the arterial vessel wall. We aim to investigate the cross-talk between different epigenetic layers of control (particularly, histone modification and non-coding RNAs) in vascular cells (e.g., endothelial and smooth muscle cells) and to define their contribution to cell-to-cell communication with immune cells in atherosclerosis.
- Role of autophagy in cardiovascular disease.
Autophagy is a crucial mechanism for cell homeostasis and resilience during environmental conditions, such as nutrient deprivation or several pathological stimuli. Classically believed as a catabolic process for bulk recycling of dysfunctional intracellular components, autophagy now emerges as a coordinated adaptive response also featuring non-degradative functions to preserve cell viability and genomic stability in response to different stressors. Stimuli relevant to cardiovascular biology (e.g., shear stress, hypoxia, lipoproteins) affect the activity of autophagy which features cell-specific adaptive roles in preserving vascular homeostasis. We aim to investigate the role of autophagy in cell types involved in atherosclerosis to identify its contribution to disease development and progression.
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We are pleased to contribute to the education of students at different stages of their academic journey.
- Master students from Human Biology Master Program at LMU
Heart, Lung and Metabolism - Practical course (Course Catalogue Reference: 19286)
- PhD candidates IRTG1123 program
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TEAM
Santovito and Weber Lab
GROUP MEMBERS
Donato Santovito, MD PhDPrincipal Investigator
Floriana Farina, PhDPostdoctoral researcherÄäüplgug Ägplugvim ävf mi
James Henderson, PhDPostdoctoral researcherQgvic-Ziumipcüuvimeävftmi
Rhoda Anane Karikari, PhDPostdoctoral researcherBdzümg Ügplogplvimeävf-mi
Mahadia KumkumPhD student
Batoul BayerM. Sc. studentjdagdbüfäY jgјipvimsävf mi
Vasiliki TriantafyllidouBioinformaticianÖgclälol-Kp;lgubgwјäDädlmüfvim ävf miAlumniElizabeth Mann Fallenbuchel, former technician Weber and Santovito Labs
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Cimen I, Natarelli L, Kichi ZA, Henderson JM, Farina FM, Briem E, Aslani M, Megens RTA, Jansen Y, Mann-Fallenbuchel E, Gencer S, Duchêne J, Nazari-Jahantigh M, van der Vorst EPC, Enard W, Döring Y, Schober A, Santovito D, Weber C. Targeting a cell-specific microRNA repressor of CXCR4 ameliorates atherosclerosis in mice. Sci Transl Med. 2023
Farina FM, Weber C, Santovito D. The emerging landscape of non-conventional RNA functions in atherosclerosis. Atherosclerosis. 2023
Santovito D, Weber C. Non-canonical features of microRNAs: paradigms emerging from cardiovascular disease. Nat Rev Cardiol. 2022
Santovito D, Toto L, De Nardis V, Marcantonio P, D’Aloisio R, Mastropasqua A, De Cesare D, Bucci M, Paganelli C, Natarelli L, Weber C, Consoli A, Mastropasqua R, Cipollone F. Plasma microRNA signature associated with retinopathy in patients with type 2 diabetes. Sci Rep. 2021
Henderson JM, Weber C, Santovito D. Beyond self-recycling: cell-specific role of autophagy in atherosclerosis. Cells. 2021
Santovito D, Egea V, Bidzhekov K, Natarelli L, Mourão A, Blanchet X, Wichapong K, Aslani M, Brunßen C, Horckmans M, Hristov M, Geerlof A, Lutgens E, Daemen MJAP, Hackeng T, Ries C, Chavakis T, Morawietz H, Naumann R, von Hundelshausen P, Steffens S, Duchêne J, Megens RTA, Sattler M, Weber C. Noncanonical inhibition of caspase-3 by a nuclear microRNA confers endothelial protection by autophagy in atherosclerosis. Sci Transl Med. 2020
Santovito D, Marcantonio P, Mastroiacovo D, Natarelli L, Mandolini C, De Nardis V, Paganelli C, De Cesare D, Affaitati G, Giamberardino MA, Stellin L, Pinelli M, Weber C, De Blasis G, Occhiuzzi U, Bucci M, Desideri G, Cipollone F. High dose rosuvastatin increases ABCA1 transporter in human atherosclerotic plaques in a cholesterol-independent fashion. Int J Cardiol. 2020
Santovito D, De Nardis V, Marcantonio P, Mandolini C, Paganelli C, Vitale E, Buttitta F, Bucci M, Mezzetti A, Consoli A, Cipollone F. Plasma Exosome MicroRNA Profiling Unravels a New Potential Modulator of Adiponectin Pathway in Diabetes: Effect of Glycemic Control. J Clin Endocrinol Metab. 2014
