Univ.-Prof. Dr. rer. nat. Ralf Gilsbach

Research area: epigenetics, chromatin biology, gene regulation, functional epigenetics, heart disease

Prof. Gilsbach is a DZHK Professor for RNA Biology of Heart Disease at the DZHK partner site Mannheim/Heidelberg, Heidelberg University Hospital. Prof. Gilsbach and his team decode and modulate disease-associated regulatory elements in the genome of cardiac cells. 

Prof. Gilsbach’s research uses multimodal methods to study epigenetic mechanisms, spatial genome organization, and RNA modifications in the heart with cell type-specific to single-cell resolution. These genome-wide studies identify distal regulatory genomic elements as central switches of heart disease. His published and ongoing studies reveal that regulatory elements dynamically interact with genes over large genomic distances in a cell-type and disease-specific manner and are enriched for non-coding risk factors. Prof Gilsbach’s lab engineers and utilizes functional epigenetic methods to steer these disease-associated regulatory elements without the risk associated with direct modification of the genetic code. These methods rely on the recruitment of epigenetic modifiers using CRISPR-based tools in an RNA-programmable manner. His lab combines them with viral delivery to dissect and perturb regulatory elements in vitro and in vivo.

Prof. Gilsbach expects that decoding and modulation of epigenetic mechanisms will allow modulation of cell type-specific genetic switches of heart disease to target pathological gene expression and cardiac remodeling. We think functional epigenetic therapy can open new avenues for precise treatment of genetic and acquired heart disease.

• Guido Tarone Award of the Heart Failure Association (ESC) (2019)
• Habilitation and PhD (“summa cum laude”) in Pharmacology and Toxicology

Laurette P, Cao C, Ramanujam D, Schwaderer M, Lueneburg T, Kuss S, Weiss L, Dilshat R, Furlong E, Rezende F, Engelhardt S, Gilsbach R. In vivo silencing of regulatory elements using a single AAV-CRISPRi vector. Circ Res. 2023 (in press)

Bednarz RL, P.; Díaz i Pedrosa, N.; Lahm, H.; Dressen, M.; Krane, M.; Streckfuß-Bömeke, M.; Gilsbach, R. Decoding promoter-enhancer interactions in human cardiac myocytes, 05 August 2022. Research Square Preprint. 2022.

Gilsbach R, Schwaderer M, Preissl S, Gruning BA, Kranzhofer D, Schneider P, Nuhrenberg TG, Mulero-Navarro S, Weichenhan D, Braun C, Dressen M, Jacobs AR, Lahm H, Doenst T, Backofen R, Krane M, Gelb BD, Hein L. Distinct epigenetic programs regulate cardiac myocyte development and disease in the human heart in vivo. Nat Commun. 2018;9:391.

Mayer SC, Gilsbach R, Preissl S, Monroy Ordonez EB, Schnick T, Beetz N, Lother A, Rommel C, Ihle H, Bugger H, Ruhle F, Schrepper A, Schwarzer M, Heilmann C, Bonisch U, Gupta SK, Wilpert J, Kretz O, von Elverfeldt D, Orth J, Aktories K, Beyersdorf F, Bode C, Stiller B, Kruger M, Thum T, Doenst T, Stoll M, Hein L. Adrenergic Repression of the Epigenetic Reader MeCP2 Facilitates Cardiac Adaptation in Chronic Heart Failure. Circ Res. 2015;117:622-633. https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.115.306721

Nothjunge S, Nuhrenberg TG, Gruning BA, Doppler SA, Preissl S, Schwaderer M, Rommel C, Krane M, Hein L, Gilsbach R. DNA methylation signatures follow preformed chromatin compartments in cardiac myocytes. Nat Commun. 2017;8:1667.

Preissl S, Schwaderer M, Raulf A, Hesse M, Gruning BA, Kobele C, Backofen R, Fleischmann BK, Hein L, Gilsbach R. Deciphering the Epigenetic Code of Cardiac Myocyte Transcription. Circ Res. 2015;117:413-423.

Gilsbach R, Preissl S, Gruning BA, Schnick T, Burger L, Benes V, Wurch A, Bonisch U, Gunther S, Backofen R, Fleischmann BK, Schubeler D, Hein L. Dynamic DNA methylation orchestrates cardiomyocyte development, maturation and disease. Nat Commun. 2014;5:5288.

CRC1550 “Molecular Circuits of Heart Disease”

SFB1425 “Heterocellular Nature of Cardiac Lesions: Identities, Interactions, Implications”