Kardiovaskuläre Erkrankungen, darunter Herzinsuffizienz (Herzschwäche), koronare Herzkrankheit und Herzinfarkt, zählen weltweit zu den häufigsten Todesursachen. Deshalb sind die weitere Forschung für eine rechtzeitige Prävention und Diagnostik sowie Entwicklung neuer Therapiestrategien für diese Erkrankungen besonders wichtig. Beim Projekt »Molekulare Mechanismen der Herzinsuffizienz« arbeiten Wissenschaflter:innen am ISAS daran, die Pathomechanismen von Herzinsuffizienz zu entschlüsseln und therapierelevante Schlüsselstrukturen auf molekularer Ebene zu identifizieren. Ziel dieser Arbeiten ist es, neue diagnostische und therapeutische Zielmoleküle (Targets) für verschiedene Herzerkrankungen wie beispielsweise Herzinsuffizienz zu identifizieren. Außerdem arbeiten die Forschenden daran, herzschädigende (kardiotoxische) Mechanismen von etwa Krebsmedikamenten aufzuklären.
Kombination von Methoden für frühe Diagnose und verbesserte Therapie
Für eine differenzierte Untersuchung sowohl einzelner Komponenten als auch ganzer zellulärer Systeme ist eine Kombination unterschiedlicher Analysemethoden notwendig. So verbinden die Forschenden in diesem Projekt unter anderem klassische Methoden der Molekulargenetik und Biochemie mit Hochdurchsatzmethoden. Sie untersuchen auch das Potenzial von kalten atmosphärischen Plasmen (Cold Atmospheric Plasma, CAP) zur Behandlung von Herzinsuffizienz.
Für eine verbesserte und frühzeitige Diagnostik der Erkrankung mittels identifizierter spezifischer Biomarker kommen bei diesem Forschungsprojekt zudem spektroskopische Bildgebungsverfahren zum Einsatz. Sie geben Aufschluss darüber, welche Rolle das Herz nicht nur bei Herzinsuffizienz, sondern auch bei Stoffwechselstörungen und Speichererkrankungen wie Morbus Fabry spielt. So ist es den Forschenden erstmal gelungen, im Mausmodell mithilfe der Coherent Anti-Stokes Raman Scattering (CARS)-Mikroskopie subtile Veränderungen im Protein-Lipid-Gehalt zwischen Herzgewebe, das von Morbus Fabry betroffen ist, und gesundem Gewebe, festzustellen. Diese Diagnosemethode hat das Potenzial, andere Diagnostik zu unterstützen, um die Beteiligung bestimmter Organe an den Erkrankungen zu ermitteln.
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Ausgewählte Publikationen
Molecular Metabolism, Bd. 79, 2023, S. 101859
Janz A, Walz K, Cirnu A, Surjanto J, Urlaub D, Leskien M, Kohlhaas M, Nickel A, Brand T, Nose N, Wörsdörfer P, Wagner N, Higuchi T, Maack C, Dudek J,…
Mutations in DNAJC19 cause altered mitochondrial structure and increased mitochondrial respiration in human iPSC-derived cardiomyocytes
https://doi.org/10.1016/j.molmet.2023.101859
Chemistry-A European Journal, Bd. 30, Nr. 11, 2023, S. e202303506
Sink A, Gerwe H, Hübner H, Boivin-Jahns V, Fender J, Lorenz K, Gmeiner P, Decker M.
"Photo-Adrenalines": ß2-Adrenergic Receptor Agonists as Molecular Probes for the Study of Spatiotemporal Adrenergic Signaling
https://doi.org/10.1002/chem.202303506
Cells, Bd. 12, Nr. 13, 2023, S. 1780
Bazgir F, Nau J, Nakhaei-Rad S, Amin E, Wolf MJ, Saucerman JJ, Lorenz K, Ahmadian MR.
The Microenvironment of the Pathogenesis of Cardiac Hypertrophy
http://doi.org/10.3390/cells12131780
Nature Communications, Bd. 14, Nr. 1, 2023
Dore R, Watson L, Hollidge S, Krause C, Sentis SC, Oelkrug R, Geißler C, Johann K, Pedaran M, Lyons G, Lopez-Alcantara N, Resch J, Sayk F, Iwen A,…
Resistance to thyroid hormone induced tachycardia in RTHα syndrome
https://doi.org/10.1038/s41467-023-38960-1
Angewandte Chemie - International Edition, Bd. 62, Nr. 49, 2023, S. e202306176
Steinmüller SAM, Fender J, Deventer MH, Tutov A, Lorenz K, Stove CP, Hislop JN, Decker M.
Visible-Light Photoswitchable Benzimidazole Azo-Arenes as β-Arrestin2-Biased Selective Cannabinoid 2 Receptor Agonists
https://doi.org/10.1002/anie.202306176
Circulation Research, Bd. 132, Nr. 4, 2023, S. 400-414
Cachorro E, Günscht M, Schubert M, Sadek MS, Siegert J, Dutt F, Bauermeister C, Quickert S, Berning H, Nowakowski F, Lämmle S, Firneburg R, Luo X,…
CNP Promotes Antiarrhythmic Effects via Phosphodiesterase 2
https://doi.org/10.1161/CIRCRESAHA.122.322031
Biomedicines, Bd. 11, Nr. 2, 2023, S. 559
Schanbacher C, Hermanns HM, Lorenz K, Wajant H, Lang I.
Complement 1q/Tumor Necrosis Factor‐Related Proteins (CTRPs): Structure, Receptors and Signaling
https://doi.org/10.3390/biomedicines11020559
Journal of Molecular and Cellular Cardiology, Bd. 2022, Nr. 173, 2022, S. S150-S150
Schanbacher C, Bieber M, Reinders Y, Teichert C, Sickmann A, Kleinschnitz C, Langhauser F, Lorenz K.
The extracellular signal-regulated kinases ERK1/2 are detrimental in ischemic stroke
https://doi.org/10.1016/j.yjmcc.2022.08.294
Nature Communications, Bd. 13, Nr. 1, 2022, S. 7648
Klapproth E, Witt A, Klose P, Wiedemann J, Vavilthota N, Künzel SR, Kämmerer S, Günscht M, Sprott D, Lesche M, Rost F, Dahl A, Rauch E, Kattner L,…
Targeting cardiomyocyte ADAM10 ectodomain shedding promotes survival early after myocardial infarction
https://doi.org/10.1038/s41467-022-35331-0
ACS Chemical Neuroscience, Bd. 13, Nr. 16, 2022, S. 2410-2435
Rodríguez-Soacha DA, Steinmüller SAM, Işbilir A, Fender J, Deventer MH, Ramírez YA, Tutov A, Sotriffer C, Stove CP, Lorenz K, Lohse MJ, Hislop JN,…
Development of an Indole-Amide-Based Photoswitchable Cannabinoid Receptor Subtype 1 (CB1R) "Cis-On" Agonist
https://doi.org/10.1021/acschemneuro.2c00160
Archives of Toxicology, Bd. 96, Nr. 8, 2022, S. 2341-2360
Merches K, Breunig L, Fender J, Brand T, Bätz V, Idel S, Kollipara L, Reinders Y, Sickmann A, Mally A, Lorenz K.
The potential of remdesivir to affect function, metabolism and proliferation of cardiac and kidney cells in vitro
https://doi.org/10.1007/s00204-022-03306-1
Frontiers in Pharmacology, Bd. 13, 2022, S. 962763
Tolstik E, Gongalsky MB, Dierks J, Brand T, Pernecker M, Pervushin NV, Maksutova DE, Gonchar KA, Samsonova JV, Kopeina G, Sivakov V, Osminkina L,…
Raman and fluorescence micro-spectroscopy applied for the monitoring of sunitinib-loaded porous silicon nanocontainers in cardiac cells
https://doi.org/10.3389/fphar.2022.962763
Proceedings of the National Academy of Sciences of the United States of America, Bd. 119, Nr. 25, 2022, S. e2121867119
Lee J, Olivieri C, Ong C, Masterson LR, Gomes S, Lee B, Schaefer F, Lorenz K, Veglia G, Rosner MR.
Raf Kinase Inhibitory Protein regulates the cAMP-dependent protein kinase signaling pathway through a positive feedback loop
https://doi.org/10.1073/pnas.2121867119
International Journal of Molecular Science, Bd. 23, Nr. Special Issue , 2022
Tolstik E, Ali N, Guo S, Ebersbach P, Möllmann D, Arias Loza A, Dierks J, Schuler I, Freier E, Debus J, Baba HA, Nordbeck P, Bocklitz T, Lorenz K.
CARS Imaging Advances Early Diagnosis of Cardiac Manifestation of Fabry Disease
https://doi.org/doi: 10.3390/ijms23105345
Cardiovascular Research, Bd. 118, Nr. 14, 2021, S. 2932-2945
Gil-Pulido J, Amézaga N, Jorgacevic I, Manthey HD, Rösch M, Brand T, Cidlinsky P, Schäfer S, Beilhack A, Saliba A, Lorenz K, Boon L, Prinz I, Waisman…
Interleukin-23 receptor expressing γδ T cells locally promote early atherosclerotic lesion formation and plaque necrosis in mice
https://doi.org/10.1093/cvr/cvab359
International Journal of Molecular Sciences, Bd. 23, Nr. 2, 2022
Schanbacher C, Bieber M, Reinders Y, Cherpokova D, Mathejka C, Nieswandt B, Sickmann A, Kleinschnitz C, Langhauser F, Lorenz K.
ERK1/2 Activity Is Critical for the Outcome of Ischemic Stroke
Frontiers in Cardiovascular Medicine, Bd. 8, 2021
Kerp H, Hönes GS, Tolstik E, Hönes-Wendland J, Gassen J, Moeller LC, Lorenz K, Führer D.
Protective Effects of Thyroid Hormone Deprivation on Progression of Maladaptive Cardiac Hypertrophy and Heart Failure
https://doi.org/10.3389/fcvm.2021.683522
IJC Heart & Vasculature, Bd. 34, 2021, S. 100781
Pfeiffer J, Lorenz K.
Murine models for heart failure: Their creation and applicability to human still require critical and careful considerations
https://doi.org/10.1016/j.ijcha.2021.100781
ACS Chemical Neuroscience, Bd. 12, Nr. 9, 2021, S. 1632-1647
Rodríguez-Soacha DA, Fender J, Ramírez YA, Collado JA, Muñoz E, Maitra R, Sotriffer C, Lorenz K, Decker M.
"Photo-Rimonabant": Synthesis and Biological Evaluation of Novel Photoswitchable Molecules Derived from Rimonabant Lead to a Highly Selective and Nanomolar " Cis-On" CB 1 R Antagonist
https://doi.org/10.1021/acschemneuro.1c00086
International Journal of Molecular Sciences, Bd. 22, Nr. 9, 2021
Wagner M, Sadeck MS, Dybkova N, Mason FE, Klehr J, Firneburg R, Cachorro E, Richter K, Klapproth E, Künzel S, Lorenz K, Heijman J, Dobrev D,…
Cellular Mechanisms of the Anti-Arrhythmic Effect of Cardiac PDE2 Overexpression
https://doi.org/10.3390/ijms22094816
Redox Biology, Bd. 41, 2021
Rhoden A, Friedrich FW, Brandt T, Raabe J, Schweizer M, Meisterknecht J, Wittig I, Ulmer BM, Klampe B, Uebeler J, Piasecki A, Lorenz K, Eschenhagen…
Sulforaphane exposure impairs contractility and mitochondrial function in three-dimensional engineered heart tissue
https://doi.org/10.1016/j.redox.2021.101951
FEBS open bio, Bd. 10, Nr. 7, 2020, S. 1210-1218
Künzel SR, Rausch JSE, Schäffer C, Hoffmann M, Künzel K, Klapproth E, Kant T, Herzog N, Küpper J, Lorenz K, Dudek S, Emig R, Ravens U, Rog-Zielinska…
Modeling atrial fibrosis in vitro - Generation and characterization of a novel human atrial fibroblast cell line
https://doi.org/10.1002/2211-5463.12896
Nature Communications, Bd. 11, Nr. 1, 2020
Tomasovic A, Brand T, Schanbacher C, Kramer S, Hümmert MW, Godoy P, Schmidt-Heck W, Nordbeck P, Ludwig J, Homann S, Wiegering A, Shaykhutdinov T,…
Interference with ERK-dimerization at the nucleocytosolic interface targets pathological ERK1/2 signaling without cardiotoxic side-effects
https://doi.org/10.1038/s41467-020-15505-4
Biochemical and Biophysical Research Communications, Bd. 520, Nr. 2, 2019, S. 327-332
Maimari T, Krasel C, Bünemann M, Lorenz K.
The N-termini of GRK2 and GRK3 simulate the stimulating effects of RKIP on β-adrenoceptors
https://doi.org/10.1016/j.bbrc.2019.09.135
ESC heart failure, Bd. 6, Nr. 5, 2019, S. 1015-1026
Jochmann S, Elkenani M, Mohamed BA, Buchholz E, Lbik D, Binder L, Lorenz K, Shah AM, Hasenfuß G, Toischer K, Schnelle M.
Assessing the role of extracellular signal-regulated kinases 1 and 2 in volume overload-induced cardiac remodelling
https://doi.org/10.1002/ehf2.12497
International Journal of Molecular Sciences, Bd. 20, Nr. 9, 2019
Breitenbach T, Lorenz K, Dandekar T.
How to Steer and Control ERK and the ERK Signaling Cascade Exemplified by Looking at Cardiac Insufficiency
https://doi.org/10.3390/ijms20092179
Clinical pharmacology and therapeutics, Bd. 2019, Nr. 5, 2018, S. 1224-1233
Müntze J, Gensler D, Maniuc O, Liu D, Cairns T, Hu K, Lorenz K, Frantz S, Wanner C, Nordbeck P.
Oral Chaperone Therapy Migalastat for Treating Fabry Disease: Enzymatic Response and Serum Biomarker Changes After 1 Year
https://doi.org/10.1002/cpt.1321
Magnetic Resonance in Medicine, Bd. 0, Nr. 0, 2018
Gensler D, Salinger T, Düring M, Lorenz K, Jahns R, Wech T, Frantz S, Ertl G, Jakob PM, Nordbeck P.
Real-time Triggered RAdial Single-Shot Inversion recovery for arrhythmia-insensitive myocardial T1 mapping: motion phantom validation and in vivo comparison.
https://doi.org/10.1002/mrm.27526
Cardiology Research and Practice, Bd. 2018, Nr. Article ID 3713897, 2018, S. 1-7
Salinger T, Hu K, Liu D, Taleh S, Herrmann S, Oder D, Gensler D, Müntze J, Ertl G, Lorenz K, Frantz S, Weidemann F, Nordbeck P.
Association between Comorbidities and Progression of Transvalvular Pressure Gradients in Patients with Moderate and Severe Aortic Valve Stenosis
https://doi.org/10.1155/2018/3713897
Molecular aspects of medicine, Bd. 63, 2018, S. 47-58
Cuello F, Wittig I, Lorenz K, Eaton P.
Oxidation of cardiac myofilament proteins: Priming for dysfunction?
https://doi.org/10.1016/j.mam.2018.08.003
PLOS One, Bd. 13, Nr. 8, 2018
Koussémou M, Lorenz K, Klotz K.
The A2B adenosine receptor in MDA-MB-231 breast cancer cells diminishes ERK1/2 phosphorylation by activation of MAPK-phosphatase-1
https://doi.org/10.1371/journal.pone.0202914
Skeletal Muscle, Bd. 8, Nr. 28, 2018
Coraspe JAG, Weis J, Anderson ME, Münchberg U, Lorenz K, Buchkremer S, Carr S, Zahedi R, Brauers E, Michels H, Sunada Y, Lochmüller H, Campbell KP,…
Biochemical and pathological changes result from mutated Caveolin-3 in muscle
https://doi.org/10.1186/s13395-018-0173-y
Circulation Cardiovascular Imaging, Bd. 11, Nr. 8, 2018
Herrmann S, Fries B, Salinger T, Liu D, Hu K, Gensler D, Strotmann J, Christa M, Beer M, Gattenlöhner S, Störk S, Voelker W, Bening C, Lorenz K, Leyh…
Myocardial Fibrosis Predicts 10-Year Survival in Patients Undergoing Aortic Valve Replacement
https://doi.org/10.1161/CIRCIMAGING.117.007131
FASEB Journal, Bd. Volume 32, Nr. No. 5, 2018
Neumann V, Knies R, Seidinger A, Simon A, Lorenz K, Matthey M, Breuer J, Wenzel D.
The β2 agonist terbutaline specifically decreases pulmonary arterial pressure under normoxia and hypoxia via α adrenoceptor antagonism
https://doi.org/10.1096/fj.201700684RR
Scientific reports, Bd. 8, 2018
Joos J, Staadatmand A, Schnabel C, Viktorinova I, Brand T, Kramer M, Nattel S, Dobrev D, Tomancak P, Backs J, Kleinbongard P, Heusch G, Lorenz K,…
Ectopic expression of S28A-mutated Histone H3 modulates longevity, stress resistance and cardiac function in Drosophila
https://doi.org/10.1038/s41598-018-21372-3
Cardiovascular Research, Bd. 114, Nr. 5, 2018, S. 641-642
Dobrev D, Lorenz K.
Age-dependent increase in c-Jun N-terminal kinase-2 activity: does this help to understand Ca2+-calmodulin-dependent protein-kinase II-mediated atrial arrhythmogenesis in human atrial fibrillation?
https://doi.org/10.1093/cvr/cvy037
Proceedings of the National Academy of Sciences of the United States of America, Bd. 114, Nr. 51, 2017
Skinner J, Wang S, Lee J, Ong C, Sommese R, Sivaramakrishnan S, Koelmel W, Hirschbeck M, Schindelin H, Kisker C, Lorenz K, Sosnick TR, Rosner MR.
A conserved salt bridge competition triggered by phosphorylation regulates the protein interactome
Thrombosis and Haemostasis, Bd. 117, Nr. 1, 2016, S. 176-187
Vorlova S, Koch M, Manthey HD, Cochain C, Busch M, Chaudhari SM, Stegner D, Yepes M, Lorenz K, Nolte MW, Nieswandt B, Zernecke A.
Coagulation factor XII induces pro-inflammatory cytokine responses in macrophages and promotes atherosclerosis in mice
https://doi.org/10.1160/TH16-06-0466
Circulation: Cardiovascular Genetics, Bd. 10, Nr. 5, 2016
Oder D, Liu D, Hu K, Üçeyler N, Salinger T, Müntze J, Lorenz K, Kandolf R, Gröne H, Sommer C, Ertl G, Wanner C, Nordbeck P.
α-Galactosidase A Genotype N215S Induces a Specific Cardiac Variant of Fabry Disease
https://doi.org/10.1161/CIRCGENETICS.116.001691
BMC Cardiovascular Disorders , Bd. 8, Nr. 7, 2016, S. 11950-11962
Salinger T, Hu K, Liu D, Herrmann S, Lorenz K, Ertl G, Nordbeck P.
Cardiac amyloidosis mimicking severe aortic valve stenosis - a case report demonstrating diagnostic pitfalls and role of dobutamine stress echocardiography
https://doi.org/10.1186/s12872-017-0519-0
Oncotarget, Bd. 8, Nr. 7, 2017, S. 11950-11962
Pott LL, Hagemann S, Reis H, Lorenz K, Bracht T, Herold T, Skryabin BV, Megger DA, Kälsch J, Weber F, Sitek B, Baba HA.
Eukaryotic elongation factor 2 is a prognostic marker and its kinase a potential therapeutic target in HCC
https://doi.org/10.18632/oncotarget.14447
Circulation Research, Bd. 120, Nr. 1, 2016, S. 120-132
Vettel C, Lindner M, Dewenter M, Lorenz K, Schanbacher C, Riedel M, Lämmle S, Meinecke S, Mason FE, Sossalla S, Geerts A, Hoffmann M, Wunder F,…
Phosphodiesterase 2 Protects Against Catecholamine-Induced Arrhythmia and Preserves Contractile Function After Myocardial Infarction
https://doi.org/10.1161/CIRCRESAHA.116.310069
Basic Research in Cardiology, Bd. 111, Nr. 66, 2016, S. 1-4
Cuello F, Lorenz K.
Inhibition of cardiac CaMKII to cure heart failure: Step by step towards translation?
https://doi.org/10.1007/s00395-016-0582-1
Molecular bioSystems, Bd. 12, Nr. 8, 2016, S. 2436-2446
Brietz A, Schuch KV, Wangorsch G, Lorenz K, Dandekar T.
Analyzing ERK 1/2 signalling and targets
https://doi.org/10.1039/C6MB00255B
Frontiers in Pharmacology, Bd. 7, 2016, S. 118
Propping S, Lorenz K, Michel MC, Wirth MP, Ravens U.
β-Adrenoceptor-mediated Relaxation of Urinary Bladder Muscle in β2-Adrenoceptor Knockout Mice
https://doi.org/10.3389/fphar.2016.00118
Biochemistry, Bd. 55, Nr. 12, 2016, S. 1909-1917
McReynolds AC, Karra AS, Li Y, Lopez ED, Turjanski AG, Dioum E, Lorenz K, Zaganjor E, Stippec S, McGlynn K, Earnest S, Cobb MH.
Phosphorylation or Mutation of the ERK2 Activation Loop Alters Oligonucleotide Binding
https://doi.org/10.1021/acs.biochem.6b00096