Ralph Knöll group
Our research aims to combine the strengths of the ICMC Regenerative Cardiology Program to foster innovative science-based strategies, technologies, and therapeutic platforms towards unraveling the epigenetic mechanisms underlying the biology of human cardiac disease.
Specific Research Objectives
1. Analysis of epigenetics, including genomic DNA methylation patterns in health and disease, unravelling of the underlying molecular mechanisms as well implementation of therapeutic strategies to exploit therapeutic potential of these modifications (together with AZ/MedImmune and Moderna Therapeutics).
2. Based on previous results, use of human genetics and genetically altered models for the development of translational studies in patients with clinically/genetically distinct forms of cardiomyopathy/CHF as a unique patient study subset, including HF-PEF (heart failure with preserved ejection fraction; KI/AZ).
3. Continuation of work in the context of the Leducq transatlantic network of excellence in regards to the evaluation of mechano-sensitive types of cell death (apoptosis or “mechanoptosis”), which includes evaluation of therapeutic interventions to avoid cardiac myocyte cell death during biomechanical stress.
|Ralph Knöll, Professor, Group leader|
Valerio Azzimato, Dr
|Zaher Elbeck, Research technician|
Payam Haftbaradaran Esfahani, PhD student
Ali Mustafa Tabish, Postdoc
|Humam Siga, Research assistent|
ZBTB17 (MIZ1) Is Important for the Cardiac Stress Response and a Novel Candidate Gene for Cardiomyopathy and Heart Failure.
Circ Cardiovasc Genet 2015 Oct;8(5):643-52
A role for membrane shape and information processing in cardiac physiology.
Pflugers Arch. 2015 Jan;467(1):167-73
Mechano-signaling in heart failure.
Pflugers Arch. 2014 Jun;466(6):1093-9
A critical role for Telethonin in regulating t-tubule structure and function in the mammalian heart.
Hum. Mol. Genet. 2013 Jan;22(2):372-83
Ventricular assist device implantation corrects myocardial lipotoxicity, reverses insulin resistance, and normalizes cardiac metabolism in patients with advanced heart failure.
Circulation 2012 Jun;125(23):2844-53
Telethonin deficiency is associated with maladaptation to biomechanical stress in the mammalian heart.
Circ. Res. 2011 Sep;109(7):758-69
A common MLP (muscle LIM protein) variant is associated with cardiomyopathy.
Circ. Res. 2010 Mar;106(4):695-704
Zebrafish integrin-linked kinase is required in skeletal muscles for strengthening the integrin-ECM adhesion complex.
Dev. Biol. 2008 Jun;318(1):92-101
Relevance of brain natriuretic peptide in preload-dependent regulation of cardiac sarcoplasmic reticulum Ca2+ ATPase expression.
Circulation 2006 Jun;113(23):2724-32
Tcap gene mutations in hypertrophic cardiomyopathy and dilated cardiomyopathy.
J. Am. Coll. Cardiol. 2004 Dec;44(11):2192-201
Asymmetric septal hypertrophy in heterozygous cMyBP-C null mice.
Cardiovasc. Res. 2004 Aug;63(2):293-304
Cardiac mechanotransduction and implications for heart disease.
J. Mol. Med. 2003 Dec;81(12):750-6
Anisotropic stretch-induced hypertrophy in neonatal ventricular myocytes micropatterned on deformable elastomers.
Biotechnol. Bioeng. 2003 Mar;81(5):578-87
Enhanced gene expression of calcium regulatory proteins in stunned porcine myocardium.
Cardiovasc. Res. 1993 Nov;27(11):2037-43
About Ralph Knöll
Professor Ralph Knöll was recruited to AstraZeneca from Imperial College where he was Professor and Chair of Myocardial Genetics from 2009 to 2014. He was formerly Professor and head of the Working Group of Cardiovascular Molecular Genetics at the Georg August University, Göttingen, Germany from 2004 to 2009. He received his professional training as a Postgraduate Researcher and then Group Leader at the Institute of Molecular Medicine, UC San Diego, from 1999 to 2004 and clinical training at the University Hospital Benjamin Franklin, Free University Berlin (Charité) from 1996 to 1999. He received his doctoral degree at the Max-Planck-Institute of Physiological and Clinical Research, Department of Experimental Cardiology, and was educated at Johann Wolfgang Goethe University Medical School, Frankfurt and Justus Liebig University Medical School, Giessen.
He received several prestigious awards, including the Fritz Acker Award of the German Cardiac Society (2007), the Theodor Frerichs Award of the German Society for Internal Medicine (2003) and an Astra Zeneca Award in Basic Science (2002).
Professor Knöll is a Member of several Editorial Boards including Basic Research in Cardiology, as well as a referee for a number of other prominent journals, including Circulation, Circulation Research, Journal of Molecular and Cellular Cardiology, European Heart Journal, Molecular and Cellular Biochemistry, European Journal of Heart Failure, and Clinical Cardiology, among others. He is also a Member of the International Society for Heart Research (ISHR), British Society for Cardiovascular Research (BSCR), European Society of Cardiology (ESC – nucleus member and treasurer of the Working Group of Myocardial Function), the American Heart Association (AHA), British Pharmacological Society (BPS) and the German Cardiac Society (DGK), among others.
He is currently active in Leducq, European Union (EU) and British Heart Foundation (BHF) grants.
He is based at AstraZeneca in Mölndal as well as at the recently established Integrated Cardio Metabolic Center at the Karolinska Institue (ICMC/KI) and has a strong interest in genetics, physiology and pharmacology of the cardiovascular system. His research aims to combine the strengths of the ICMC Regenerative Cardiology Program to foster innovative science-based strategies, technologies, and therapeutic platforms towards unraveling the epigenetic mechanisms underlying the biology of human cardiac disease. The program will capitalize on the internal strengths of KI in the fields of regenerative/developmental/human stem cell biology in general, unique and well-curated patient registries and human tissue/cell resources.
His program will integrate the strengths of AstraZeneca in terms of drug development know-how, chemical screening, larger scale biology/bioinformatics/higher throughput capacity, regulatory and toxicology expertise, large animal model systems, and larger scale production. Also, he will take advantage of AZ/MedImmune (recombinant protein/peptide design and production, biological therapeutics know-how) and collaboration with Moderna Therapeutics (synthetic modified mRNA therapeutics for cardiovascular disease in general).