Research areas: epigenetic regulatory mechanisms in the myocardium
Prof. Backs is DZHK Professor for Epigenetic Regulatory Mechanisms in the Myocardium, Director of the Institute of Experimental Cardiology at the Heidelberg University Hospital, and the Speaker of the DZHK partner site Heidelberg/Mannheim.
Prof. Backs and his coworkers try to understand how the environment and frequent comorbidities, including stress, diabetes, or cancer, interact at the molecular level with the cardiac genome and lead to heart failure. Prof. Backs was one of the first who dissected the functions and mechanisms of epigenetic enzymes that transduce stress signals to the cardiac genome. His team contributed paradigm-shifting research findings, showing that cardiac dysfunction is driven by specific metabolic and inflammatory mediators leading through epigenetic enzymes to coordinated changes in gene expression causative for cardiac dysfunction. For instance, he discovered that lipid droplet-associated proteins control cardiac function through regulated proteolysis of a histone deacetylase (Jebessa et al., Nat Metab. 2019), which then, in turn, serves as a key regulator of protein O-GlcNAcylation and cardiac contractility (Lehmann et al., Nat Med 2018). These pathways are modulated by direct interactions with protein kinases. One identified mechanism led to a drug-development program (CaMKII-HDAC4 inhibitory compounds) that is currently supported by a Translational Research Project (TRP) of the DZHK. The work of the Backs lab suggests that this type of new drugs would be in particular useful for patients with heart failure and diabetes (Kronlage et al., Circulation 2018). Current projects focus on different hereditary forms of heart failure, such as RBM20 cardiomyopathy but also on the contribution of gene expression to acute heart failure caused by inflammation or emotional stress. With his DZHK professorship, Prof. Backs became the inaugural Director of the Institute of Experimental Cardiology at Heidelberg University Hospital that is currently expanding and recruiting more DZHK professors for RNA Biology and Chromatin Remodeling.
Major achievements and awards
- Elected as Vice-Chair for the Gordon Research Conference (GRC) on Epigenetic Regulation of Cardiovascular Disease in 2021 (Chair in 2023) (2019)
- Arthur-Weber Award, German Cardiac Society (DGK) (2017)
- Outstanding Investigator Award from the International Society of Heart Research (ISHR) (2016)
- Outstanding Achievement Award from the Council on Basic Cardiovascular Science of the European Society of Cardiology (CBCS) (2015)
- Outstanding Early Investigator Award from the Basic Cardiovascular Science Council (BCVS) of the American Heart Association (AHA) (2015)
Jebessa ZH, Shanmukha Kumar D, Dewenter M, Lehmann LH, Xu C, Schreiter F, Siede D, Gong XM, Worst BC, Federico G, Sauer SW, Fischer T, Wechselberger L, Muller OJ, Sossalla S, Dieterich C, Most P, Grone HJ, Moro C, Oberer M, Haemmerle G, Katus HA, Tyedmers J and Backs J. The lipid droplet-associated protein ABHD5 protects the heart through proteolysis of HDAC4. Nat Metab. 2019;1:1157-1167.
Saadatmand AR, Sramek V, Weber S, Finke D, Dewenter M, Sticht C, Gretz N, Wustemann T, Hagenmueller M, Kuenzel SR, Meyer-Roxlau S, Kramer M, Sossalla S, Lehmann LH, Kammerer S, Backs J* and El-Armouche A*. CaM kinase II regulates cardiac hemoglobin expression through histone phosphorylation upon sympathetic activation. Proc Natl Acad Sci U S A. 2019;116:22282-22287. * Contributed equally
Kronlage M, Dewenter M, Grosso J, Fleming T, Oehl U, Lehmann LH, Falcao-Pires I, Leite-Moreira AF, Volk N, Grone HJ, Muller OJ, Sickmann A, Katus HA and Backs J. O-GlcNAcylation of Histone Deacetylase 4 Protects the Diabetic Heart From Failure. Circulation. 2019;140:580-594.
Toth AD, Schell R, Levay M, Vettel C, Theis P, Haslinger C, Alban F, Werhahn S, Frischbier L, Krebs-Haupenthal J, Thomas D, Grone HJ, Avkiran M, Katus HA, Wieland T and Backs J. Inflammation leads through PGE/EP3 signaling to HDAC5/MEF2-dependent transcription in cardiac myocytes. EMBO Mol Med. 2018;10.
Lehmann LH, Jebessa ZH, Kreusser MM, Horsch A, He T, Kronlage M, Dewenter M, Sramek V, Oehl U, Krebs-Haupenthal J, von der Lieth AH, Schmidt A, Sun Q, Ritterhoff J, Finke D, Volkers M, Jungmann A, Sauer SW, Thiel C, Nickel A, Kohlhaas M, Schafer M, Sticht C, Maack C, Gretz N, Wagner M, El-Armouche A, Maier LS, Londono JEC, Meder B, Freichel M, Grone HJ, Most P, Muller OJ, Herzig S, Furlong EEM, Katus HA and Backs J. A proteolytic fragment of histone deacetylase 4 protects the heart from failure by regulating the hexosamine biosynthetic pathway. Nat Med. 2018;24:62-72.
Dewenter M, von der Lieth A, Katus HA and Backs J. Calcium Signaling and Transcriptional Regulation in Cardiomyocytes. Circ Res. 2017;121:1000-1020.
Lehmann LH, Rostosky JS, Buss SJ, Kreusser MM, Krebs J, Mier W, Enseleit F, Spiger K, Hardt SE, Wieland T, Haass M, Luscher TF, Schneider MD, Parlato R, Grone HJ, Haberkorn U, Yanagisawa M, Katus HA and Backs J. Essential role of sympathetic endothelin A receptors for adverse cardiac remodeling. Proc Natl Acad Sci U S A. 2014;111:13499-504.
Weinreuter M, Kreusser MM, Beckendorf J, Schreiter FC, Leuschner F, Lehmann LH, Hofmann KP, Rostosky JS, Diemert N, Xu C, Volz HC, Jungmann A, Nickel A, Sticht C, Gretz N, Maack C, Schneider MD, Grone HJ, Muller OJ, Katus HA and Backs J. CaM Kinase II mediates maladaptive post-infarct remodeling and pro-inflammatory chemoattractant signaling but not acute myocardial ischemia/reperfusion injury. EMBO Mol Med. 2014;6:1231-45.
Kreusser MM, Lehmann LH, Keranov S, Hoting MO, Oehl U, Kohlhaas M, Reil JC, Neumann K, Schneider MD, Hill JA, Dobrev D, Maack C, Maier LS, Grone HJ, Katus HA, Olson EN and Backs J. Cardiac CaM Kinase II genes delta and gamma contribute to adverse remodeling but redundantly inhibit calcineurin-induced myocardial hypertrophy. Circulation. 2014;130:1262-73.
Backs J, Worst BC, Lehmann LH, Patrick DM, Jebessa Z, Kreusser MM, Sun Q, Chen L, Heft C, Katus HA and Olson EN. Selective repression of MEF2 activity by PKA-dependent proteolysis of HDAC4. J Cell Biol. 2011;195:403-15.