Question 2

What are the molecular determinants that underlie cardiac fibroblast activation and diversification in the context of ischemic injury and heart failure?

We will utilize state of the art single cell and spatial genomic tools in human and mouse to dissect mesenchymal cell heterogeneity and identify cellular and molecular drivers of cardiac fibrosis and cross-talk to immune cells with the ultimate goal to identify novel therapeutic targets for patients suffering from heart failure. We will extend these studies to dissect the genetic pathways that influence the identity, abundance, and function of cardiac fibroblasts in homeostasis and disease by establishing a variation-to-disease validation pipeline that leverages naturally occurring genetic diversity in well characterized, full sequenced mouse strains. Key identified pathways will be validated by CRISPR/Cas9 based modeling in vitro and in vivo.
We will utilize state of the art single cell and spatial genomic tools in human and mouse to dissect mesenchymal cell heterogeneity and identify cellular and molecular drivers of cardiac fibrosis and cross-talk to immune cells with the ultimate goal to identify novel therapeutic targets for patients suffering from heart failure. We will extend these studies to dissect the genetic pathways that influence the identity, abundance, and function of cardiac fibroblasts in homeostasis and disease by establishing a variation-to-disease validation pipeline that leverages naturally occurring genetic diversity in well characterized, full sequenced mouse strains. Key identified pathways will be validated by CRISPR/Cas9 based modeling in vitro and in vivo.

“We propose that integrative single cell and spatial genomic technologies allow to dissect the cellular heterogeneity of cardiac fibrosis driving mesenchymal cells and their mechanisms of activation to guide the development of novel therapies for patients with heart failure.”

Rafael Kramann, RWTH Aachen University, Senior Investigator- Q2

Network Members

Rafael Kramann, MD, PhD

Rafael Kramann, MD, PhD

RWTH Aachen University, Senior Investigator – Question 2

Christoph Kuppe, MD

Christoph Kuppe, MD

RWTH Aachen University, Early Career Investigator – Question 2

Turgay Saritas, MD

Turgay Saritas, MD

RWTH Aachen University, Early Career Investigator – Question 2

David Schumacher, MD

David Schumacher, MD

RWTH Aachen University, Early Career Investigator – Question 2

Sikander Hayat, PhD

Sikander Hayat, PhD

RWTH Aachen University, Early Career Investigator – Question 2

Nadia Rosenthal, PhD

Nadia Rosenthal, PhD

The Jackson Laboratory & Imperial College London, Senior Investigator – Question 2

John Bachman, PhD

John Bachman, PhD

The Jackson Laboratory, Early Career Investigator – Question 2

Susanne Sattler, PhD

Susanne Sattler, PhD

Imperial College, Early Career Investigator – Question 2