Top-NOTCH approach to pathological changes of congenital heart disease

• Applicant: Professor Dr. Marc-Phillip Hitz, Ph.D.
• Subject Area: Cardiology, Angiology ; Pediatric and Adolescent Medicine
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 531193580

Congenital heart diseases (CHD) affect 7/1000 births and form a majority of all clinically important birth defects. In a genetic study of patients with CHD, we found a high prevalence of CHD cases with rare variants in the NOTCH1 Gen. This makes NOTCH1 signaling a major player involved in CHD. In WP1, we plan to introduce human NOTCH1 variants from three patients into a mouse and establish humanized models. Consequently, we will perform a detailed characteristic at various developmental stages for morphological and physiological changes. We will compare the gain of function humanized mice models to conditional NOTCH1 loss of function mice. In WP2, our collaborators will perform single-cell sequencing to analyze mechanisms involved in the development of CHD at cellular resolution. In WP3, we will visualize and evaluate heart tissue changes and analyze coronary vasculature development based on the findings from the previous WP with our newly developed methodology. We plan to perform a detailed development analysis of NOTCH1-related CHD in humanized mouse models and identify essential time points for prenatal diagnosis of CHD.

• DFG Programme: Research Grants
• International Connection: Czech Republic
• Cooperation Partner: Dr. Hana Kolesova, Ph.D.