Research areas: vascular disease, atherosclerosis, aortic aneurysm, non-coding RNA
Lars Maegdefessel is a DZHK Junior Group Leader at the Klinikum rechts der Isar of the Technical University Munich. His research focuses on the therapeutic and biomarker potential of non-coding RNAs in vascular diseases.
Lars Maegdefessel’s Experimental Vascular Medicine unit at the TUM is focused on the therapeutic and biomarker potential of non-coding RNAs in vascular disease and its underlying (patho-)mechanisms, such as atherosclerosis, aneurysm formation, inflammation, and thrombosis. His research team utilizes unique human biobank material and various pre-clinical experimental models to unravel novel treatment and detection methods on a molecular basis to combat the burden of cardiovascular diseases. The traditional method of drug design and biomarker discovery, involving enzymes, cell surface receptors, and other proteins, has not really impacted the treatment and detection of cardiovascular diseases (CVDs) to a greater extent in the recent past, which is mainly due to the sensitive nature of the targeted system. The discovery of an entirely new method of regulation and recognition by non-coding RNAs (e.g., microRNAs, long non-coding RNAs, circular RNAs) and their validation as markers and modulators of pathological conditions, provides new hope for innovative therapy and disease recognition approaches. The Experimental Vascular Medicine lab in Munich utilizes unique human biobank material (tissue and plasma) of different CVDs. Most recently the group is exploring the role of microRNAs and lncRNAs in stable and unstable atherosclerotic plaques (from patients with symptomatic and asymptomatic carotid stenosis), aortic aneurysms (thoracic and abdominal), peripheral vascular occlusive disease (PVOD), in-stent restenosis (ISR), as well as transplantation and radiation vasculopathy. Candidate ncRNAs and their putative gene (mRNA) targets and proteins are profiled and detected through different transcriptomic (RNA sequencing, microarrays), proteomic, epigenomic and genetic analyses applications. Discoveries from human profiling studies are extensively investigated in pre-clinical models of CVD, allowing the lab to better understand the physiological and pathological function and dysfunction of ncRNA modulation.
AHA Scientific News on Sex Differences in Vascular Diseases:
AHA Scientific News on Genomic Tools in CVD:
Major achievements and awards
- ERC Starting Grant 2016
- Heisenberg Stipend and Professorship (DFG) 2016
- Werner Risau Award in Vascular Biology of the American Heart Association (AHA) 2016
- Prince Daniel Research Award of the Swedish Heart and Lung Foundation (HLF) 2014
- Ragnar Söderberg Fellowship in Medicine 2014
Centa M, Jin H, Hofste L, Hellberg S, Busch A, Baumgartner R, Verzaal NJ, Lind Enoksson S, Perisic Matic L, Boddul SV, Atzler D, Li DY, Sun C, Hansson GK, Ketelhuth DFJ, Hedin U, Wermeling F, Lutgens E, Binder CJ, Maegdefessel L, Malin SG. Germinal Center-Derived Antibodies Promote Atherosclerosis Plaque Size and Stability. Circulation. 2019 May 21;139(21):2466-2482.
Li DY, Busch A, Jin H, Chernogubova E, Pelisek J, Karlsson J, Sennblad B, Liu S, Lao S, Hofmann P, Bäcklund A, Eken SM, Roy J, Eriksson P, Dacken B, Ramanujam P, Dueck A, Engelhardt S, Boon RA, Eckstein HH, Spin JM, Tsao PS, Maegdefessel L. H19 induces abdominal aortic aneurysm development and progression. Circulation. 2018; 138:1551-1568.
Jin H, Li DY, Chernogubova E, Sun C, Busch A, Eken SM, Saliba-Gustafsson P, Winter H, Winski G, Raaz U, Schellinger IN, Simon N, Hegenloh R, Matic LP, Jagodic M, Ehrenborg E, Pelisek J, Eckstein HH, Hedin U, Backlund A, Maegdefessel L. Local Delivery of miR-21 Stabilizes Fibrous Caps in Vulnerable Atherosclerotic Lesions. Mol Ther. 2018; 26:1040-1055.
Kojima Y, Werner N, Ye J, Nanda V, Tsao N, Wang Y, Flores AM, Miller CL, Weissman I, Deng H, Xu B, Dalman RL, Eken SM, Pelisek J, Li Y, Maegdefessel L, Leeper NJ. Proefferocytotic Therapy Promotes Transforming Growth Factor beta Signaling and Prevents Aneurysm Formation. Circulation. 2018; 137:750-753.
Eken SM, Jin H, Chernogubova E, Li Y, Simon N, Sun C, Korzunowicz G, Busch A, Bäcklund A, Österholm C, Razuvaev A, Renné T, Eckstein HH, Pelisek J, Eriksson P, Gonzalez Diez M, Matic Perisic LP, Schellinger IN, Raaz U, Leeper NJ, Hansson GK, Paulsson-Berne G, Hedin U, Maegdefessel L. MicroRNA-210 Enhances Fibrous Cap Stability in Advanced Atherosclerotic Lesions. Circ Res. 2017; 120:633-44.
Kojima Y, Volkmer JP, McKenna K, Civelek M, Lusis AJ, Miller CL, Direnzo D, Nanda V, Ye J, Connolly AJ, Schadt EE, Quertermous T, Betancur P, Maegdefessel L, Matic LP, Hedin U, Weissman IL, Leeper NJ. CD47-blocking antibodies restore phagocytosis and prevent atherosclerosis. Nature. 2016; 536: 86-90.
Wang D, Deuse T, Stubbendorff M, Chernogubova E, Erben RG, Eken SM, Jin H, Li Y, Busch A, Heeger CH, Behnisch B, Reichenspurner H, Robbins RC, Spin JM, Tsao PS, Schrepfer S, Maegdefessel L. Local MicroRNA Modulation Using a Novel Anti-miR-21-Eluting Stent Effectively Prevents Experimental In-Stent Restenosis. Arterioscler Thromb Vasc Biol. 2015; 35(9):1945-53.
Maegdefessel L, Spin JM, Raaz U, Adam M, Azuma J, Toh RM, Deng A, Chernogubova E, Eken SM, Jin H, Roy J, Hultgren R, Caidahl K, Schrepfer S, Mc Connell MV, Hamsten A, Eriksson P, Dalman RL, Tsao PS. miR-24 limits aortic vascular inflammation and murine abdominal aortic aneurysm development. Nat Commun. 2014; 5:5214.
Maegdefessel L, Azuma J, Toh RM, Merk DR, Deng A, Raiesdana A, Leeper NJ, Raaz, U, Schoelmerich A, Mc Connell MV, Dalman RL, Spin JM, Tsao PS. Induction of microRNA-21 blocks abdominal aortic aneurysm development and nicotine-augmented expansion. Sci Transl Med. 2012; 4:122ra22.