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Targeting perivascular myofibroblast progenitors to treat cardiac fibrosis and heart failure in chronic kidney disease

Total Cost €


EC-Contrib. €






 CureCKDHeart project word cloud

Explore the words cloud of the CureCKDHeart project. It provides you a very rough idea of what is the project "CureCKDHeart" about.

cardiovascular    homeostasis    cardiomyopathy    proteasome    gli1    treat    die    utilize    editing    population    screens    cardiomyocytes    patients    throughput    tracing    chronic    myofibroblast    ablation    vivo    ventricular    expertise    mostly    recurrent    experiments    genetic    scientists    physician    perivascular    hypertrophy    ckd    death    remodeling    pathophysiologic    disease    hypothesis    immortalized    ameliorates    profiling    crispr    carries    fibrosis    mouse    critical    chemists    breakthrough    mortality    progenitors    mechanism    physiologists    cardiac    therapeutics    passion    left    drives    activation    inhibitory    massively    communication    interdisciplinary    rescues    sudden    genome    therapies    untangle    kidney    cells    compounds    assays    sought    health    function    critically    rarefaction    heart    fate    aging    uremia    biomedical    models    uremic    cas9    premature    endothelial    public    cell    capillary    progenitor    druggable    precusors    transcript    perform   

Project "CureCKDHeart" data sheet

The following table provides information about the project.


Organization address
address: Pauwelsstrasse 30
city: AACHEN
postcode: 52074

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Total cost 1˙497˙888 €
 EC max contribution 1˙497˙888 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-STG
 Funding Scheme ERC-STG
 Starting year 2016
 Duration (year-month-day) from 2016-05-01   to  2021-04-30


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITAETSKLINIKUM AACHEN DE (AACHEN) coordinator 1˙497˙888.00


 Project objective

Chronic kidney disease (CKD) is a growing public health problem with a massively increased cardiovascular mortality. Patients with advanced CKD mostly die from sudden cardiac death and recurrent heart failure due to premature cardiac aging with hypertrophy, fibrosis, and capillary rarefaction. I have recently identified the long sought key cardiac myofibroblast progenitor population, an emerging breakthrough that carries the potential to develop novel targeted therapeutics. Genetic ablation of these Gli1 perivascular progenitors ameliorates fibrosis, cardiac hypertrophy and rescues left-ventricular function. I propose that Gli1 cells are critically involved in all major pathophysiologic changes in cardiac aging and uremic cardiomyopathy including fibrosis, hypertrophy and capillary rarefaction. I will perform state of the art genetic fate tracing, ablation and in vivo CRISPR/Cas9 genome editing experiments to untangle their complex mechanism of activation and communication with endothelial cells and cardiomyocytes promoting fibrosis, capillary rarefaction, cardiac hypertrophy and heart failure. To identify novel druggable targets I will utilize new mouse models that allow comparative transcript and proteasome profiling assays of these critical myofibroblast precusors in homeostasis, aging and premature aging in CKD. Novel assays with immortalized cardiac Gli1 cells will allow high throughput screens to identify uremia associated factors of cell activation and inhibitory compounds to facilitate the development of novel therapeutics. This ambitious interdisciplinary project requires the expertise of chemists, physiologists, biomedical researchers and physician scientists to develop novel targeted therapies in cardiac remodeling during aging and CKD. The passion that drives this project results from a simple emerging hypothesis: It is possible to treat heart failure and sudden cardiac death in aging and CKD by targeting perivascular myofibroblast progenitors.


year authors and title journal last update
List of publications.
2016 Rafael Kramann, Claudia Goettsch, Janewit Wongboonsin, Hiroshi Iwata, Rebekka K. Schneider, Christoph Kuppe, Nadine Kaesler, Monica Chang-Panesso, Flavia G. Machado, Susannah Gratwohl, Kaushal Madhurima, Joshua D. Hutcheson, Sanjay Jain, Elena Aikawa, Benjamin D. Humphreys
Adventitial MSC-like Cells Are Progenitors of Vascular Smooth Muscle Cells and Drive Vascular Calcification in Chronic Kidney Disease
published pages: 628-642, ISSN: 1934-5909, DOI: 10.1016/j.stem.2016.08.001
Cell Stem Cell 19/5 2019-07-08
2017 Rebekka K. Schneider, Ann Mullally, Aurelien Dugourd, Fabian Peisker, Remco Hoogenboezem, Paulina M.H. Van Strien, Eric M. Bindels, Dirk Heckl, Guntram Büsche, David Fleck, Gerhard Müller-Newen, Janewit Wongboonsin, Monica Ventura Ferreira, Victor G. Puelles, Julio Saez-Rodriguez, Benjamin L. Ebert, Benjamin D. Humphreys, Rafael Kramann
Gli1 + Mesenchymal Stromal Cells Are a Key Driver of Bone Marrow Fibrosis and an Important Cellular Therapeutic Target
published pages: 785-800.e8, ISSN: 1934-5909, DOI: 10.1016/j.stem.2017.03.008
Cell Stem Cell 20/6 2019-07-08
2017 Rafael Kramann, Janewit Wongboonsin, Monica Chang-Panesso, Flavia G. Machado, Benjamin D. Humphreys
Gli1 + Pericyte Loss Induces Capillary Rarefaction and Proximal Tubular Injury
published pages: 776-784, ISSN: 1046-6673, DOI: 10.1681/ASN.2016030297
Journal of the American Society of Nephrology 28/3 2019-07-08
2018 Hélène FE Gleitz, Rafael Kramann, Rebekka K Schneider
Understanding deregulated cellular and molecular dynamics in the haematopoietic stem cell niche to develop novel therapeutics for bone marrow fibrosis
published pages: 138-146, ISSN: 0022-3417, DOI: 10.1002/path.5078
The Journal of Pathology 245/2 2019-05-04
2018 Leon J. Schurgers, Asim C. Akbulut, Dawid M. Kaczor, Maurice Halder, Rory R. Koenen, Rafael Kramann
Initiation and Propagation of Vascular Calcification Is Regulated by a Concert of Platelet- and Smooth Muscle Cell-Derived Extracellular Vesicles
published pages: , ISSN: 2297-055X, DOI: 10.3389/fcvm.2018.00036
Frontiers in Cardiovascular Medicine 5 2019-05-04
2018 Rafael Kramann, Flavia Machado, Haojia Wu, Tetsuro Kusaba, Konrad Hoeft, Rebekka K. Schneider, Benjamin D. Humphreys
Parabiosis and single-cell RNA sequencing reveal a limited contribution of monocytes to myofibroblasts in kidney fibrosis
published pages: , ISSN: 2379-3708, DOI: 10.1172/jci.insight.99561
JCI Insight 3/9 2019-05-04

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