{"id":1186,"date":"2021-06-07T11:52:19","date_gmt":"2021-06-07T11:52:19","guid":{"rendered":"https:\/\/www.embl.org\/about\/info\/mmpu\/?page_id=1186"},"modified":"2025-10-31T08:22:39","modified_gmt":"2025-10-31T08:22:39","slug":"heart-development-and-disease","status":"publish","type":"page","link":"https:\/\/www.embl.org\/about\/info\/mmpu\/research-groups\/heart-development-and-disease\/","title":{"rendered":"Heart Development and Disease"},"content":{"rendered":"\n
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Group leaders: Eileen Furlong and Johannes Backs<\/h2>\n\n\n\n

Our research interest<\/h3>\n\n\n\n

Our team focuses on both fundamental and translational aspects of chromatin biology in the context of human heart development and disease including cardiomyopathies and acquired forms of acute\/chronic heart failure. These heart diseases represent the most frequent underlying cause of death in western countries and thereby need an in depth investigation to develop new approaches to pave the way towards new translational approaches. Specific areas of interest include the mechanisms of epigenetic regulation down to the single cell level and the generation of tractable human in vitro<\/em> 3D models (cardioids) that recapitulate the early steps of heart development and disease.<\/p>\n\n\n\n

Background<\/h3>\n\n\n\n

Although a number of morphological heart defects can be addressed surgically, the genetic causes persist, and eventually result in heart failure and arrhythmias in adults. Mutations in transcription factors or chromatin modifiers lead to congenital heart disease, but very little is known about the pathomechanisms linking the specific genetic causes to cardiac dysfunction in adults. Mutations in chromatin modifying enzymes do not only cause neonatal and adult heart disease due to misregulation of gene expression, but also by stress-induced regulatory mechanisms that lead to secondarily heart disease.<\/p>\n\n\n\n

Goals<\/h3>\n\n\n\n

This program aims to develop a human in vitro<\/em> 3D model that recapitulates the early steps of heart development to form a 3D heart tube, which we will further exploit to make more complex heart organoids. Such a model will provide a genetically tractable system to study the molecular basis of both human heart development and genetic heart disease, especially when combined with gene perturbations and state-of-the-art single-cell technologies. We will use single-cell approaches (such as scATAC-seq) to follow the developmental trajectories of iPS cell differentiation with different protocols to develop a 3D system that best recapticulates human heart development. Having such 3D heart models in hand will enable a characterization of the functional impact of disease associated genetic variants. Chromatin remodeling will be assessed after genetic perturbations and also upon inflammatory stress, which we previously discovered leads to an acute de-compaction of chromatin. The combined expertise of both groups may lead to synergies to discover fundamental principles with translational potential to combat inherited and acquired heart disease.<\/p>\n\n\n\n

\n\nSelected publications<\/summary>\n
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The lipid droplet-associated protein ABHD5 protects the heart through proteolysis of HDAC4.<\/a>
Jebessa ZH, Shanmukha KD, Dewenter M, Lehmann LH, Xu C, Schreiter F, Siede D, Gong XM, Worst BC, Federico G, Sauer SW, Fischer T, Wechselberger L, M\u00fcller OJ, Sossalla S, Dieterich C, Most P, Gr\u00f6ne HJ, Moro C, Oberer M, Haemmerle G, Katus HA, Tyedmers J, Backs J. Nat Metab. 2019 Nov;1(11):1157-1167. doi: 10.1038\/s42255-019-0138-4. Epub 2019 Nov 15. PMID: 31742248<\/p>\n\n\n\n

Highly rearranged chromosomes reveal uncoupling between genome topology and gene expression.<\/a>
Ghavi-Helm Y, Jankowski A, Meiers S, Viales RR, Korbel JO, Furlong EEM. Nat Genet. 2019 Aug;51(8):1272-1282. doi: 10.1038\/s41588-019-0462-3. Epub 2019 Jul 15. PMID: 31308546<\/p>\n\n\n\n

O-GlcNAcylation of Histone Deacetylase 4 Protects the Diabetic Heart From Failure.<\/a>
Kronlage M, Dewenter M, Grosso J, Fleming T, Oehl U, Lehmann LH, Falc\u00e3o-Pires I, Leite-Moreira AF, Volk N, Gr\u00f6ne HJ, M\u00fcller OJ, Sickmann A, Katus HA, Backs J. Circulation. 2019 Aug 13;140(7):580-594. doi: 10.1161\/CIRCULATIONAHA.117.031942. Epub 2019 Jun 14. PMID: 31195810<\/p>\n\n\n\n

Inflammation leads through PGE\/EP3<\/sub> signaling to HDAC5\/MEF2-dependent transcription in cardiac myocytes.<\/a>
T\u00f3th AD, Schell R, L\u00e9vay M, Vettel C, Theis P, Haslinger C, Alban F, Werhahn S, Frischbier L, Krebs-Haupenthal J, Thomas D, Gr\u00f6ne HJ, Avkiran M, Katus HA, Wieland T, Backs J. EMBO Mol Med. 2018 Jul;10(7):e8536. doi: 10.15252\/emmm.201708536. PMID: 29907596<\/p>\n\n\n\n

The cis-regulatory dynamics of embryonic development at single-cell resolution.<\/a>
Cusanovich DA, Reddington JP, Garfield DA, Daza RM, Aghamirzaie D, Marco-Ferreres R, Pliner HA, Christiansen L, Qiu X, Steemers FJ, Trapnell C, Shendure J, Furlong EEM. Nature. 2018 Mar 22;555(7697):538-542. doi: 10.1038\/nature25981. Epub 2018 Mar 14. PMID: 29539636<\/p>\n\n\n\n

A proteolytic fragment of histone deacetylase 4 protects the heart from failure by regulating the hexosamine biosynthetic pathway.<\/a>
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, V\u00f6lkers M, Jungmann A, Sauer SW, Thiel C, Nickel A, Kohlhaas M, Sch\u00e4fer M, Sticht C, Maack C, Gretz N, Wagner M, El-Armouche A, Maier LS, Londo\u00f1o JEC, Meder B, Freichel M, Gr\u00f6ne HJ, Most P, M\u00fcller OJ, Herzig S, Furlong EEM, Katus HA, Backs J. Nat Med. 2018 Jan;24(1):62-72. doi: 10.1038\/nm.4452. Epub 2017 Dec 11. PMID: 29227474<\/p>\n\n\n\n

Genetic variants regulating expression levels and isoform diversity during embryogenesis.<\/a>
Cannav\u00f2 E, Koelling N, Harnett D, Garfield D, Casale FP, Ciglar L, Gustafson HE, Viales RR, Marco-Ferreres R, Degner JF, Zhao B, Stegle O, Birney E, Furlong EE. Nature. 2017 Jan 19;541(7637):402-406. doi: 10.1038\/nature20802. Epub 2016 Dec 26. PMID: 28024300<\/p>\n\n<\/div>\n<\/details>\n\n\n\n

\n\nGroup members<\/summary>\n
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Farhad Bazgir, PhD<\/strong>
Postdoc
Backs Group
Heidelberg University Hospital, Institute of Experimental Cardiology
Phone: +49 6221 56 35271
farhad.bazgir@cardioscience.uni-heidelberg.de <\/a><\/p>\n\n\n\n

Javier Duran, PhD<\/strong>
Postdoc
Backs Group
Heidelberg University Hospital, Institute of Experimental Cardiology
Phone: +49 6221 56 35271
Javier.Duran@med.uni-heidelberg.de <\/a><\/p>\n\n\n\n

Victoria Mauz, MD<\/strong>
PhD student (EMBL International PhD Programme – EIPP)
Backs Group
Heidelberg University Hospital, Institute of Experimental Cardiology
Phone: +49 6221 56-7214
victoria.mauz@med.uni-heidelberg.de<\/a><\/p>\n\n\n\n

Eric Schoger, PhD<\/strong>
Postdoc
Backs Group
Heidelberg University Hospital, Institute of Experimental Cardiology
Phone: +49 6221 56 35271
eric.schoger@cardioscience.uni-heidelberg.de<\/a><\/p>\n\n\n\n

Hans Siegrist, MD<\/strong>
Clinician Scientist
Backs Group
Heidelberg University Hospital, Institute of Experimental Cardiology
Phone: +49 6221 56 35271
Hans.Siegrist@med.uni-heidelberg.de<\/a><\/p>\n\n\n\n

Annika Vogler<\/strong>
PhD student (EMBL International PhD Programme – EIPP)
Furlong Group, EMBL
Phone: +49 6221 387-8426
<\/a>annika.vogler@embl.de<\/a><\/p>\n\n\n\n

Xin Wang , PhD<\/strong>
Bioinformatician
Furlong Group, EMBL
wang.xin@embl.de<\/a><\/p>\n\n\n\n

<\/p>\n\n<\/div>\n<\/details>\n\n\n\n

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\n \n On this page\n <\/h3>\n \n \n

    \r\n \t
  • Our research interest<\/li>\r\n \t
  • Background<\/li>\r\n \t
  • Goal<\/li>\r\n \t
  • Selected publications<\/li>\r\n \t
  • Group members<\/li>\r\n<\/ul><\/p>\n <\/div>\n<\/article>\n\n<\/div>\n<\/div>\n<\/div>\n\n\n\n

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