Project Details
Projekt
Assessment of Cellular and Molecular Architecture of Human Hypertrophic Cardiomyopathy utilizing Single-Cell Technologies
Applicant
Dr. Meraj Neyazi
Subject Area
Cardiology, Angiology
Term
since 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 505244757
Hypertrophic cardiomyopathy (HCM) is one of the most common genetic heart diseases, affecting 1 in 500 people in the general population and 20 million people globally. Patients with HCM can suffer from severe symptoms at a young age like exertional dyspnea, angina, palpitations, atrial fibrillation, heart failure or even sudden cardiac death. HCM can be caused by autosomal dominant mutations, with multiple genes of the sarcomere in the contractile components or related structures being involved, which makes genetic testing an important pillar in diagnosis and treatment of patients with HCM. 70 – 80% of the known mutations are located in genes that encode for myosin heavy chain 7 (MYH7) and myosin binding protein c (MYBPC3), which are both localized in the thick filament of the sarcomere. Yet, in many cases HCM is not variant positive, but unexplained, possibly being caused by variants of unknown significance or de novo mutations. It is crucial to shed more light into the mechanisms that lead to this disease phenotype to not only improve our understanding, but also to generate novel and better treatment options for affected individuals.Novel technologies, such as single-cell sequencing, make it possible to study diseases from a new perspective, revealing new insights. In contrast to other former sequencing methods, which provide an average of the cells in one tissue, single-cell sequencing respects the heterogeneity of cell types and cell states within one tissue, yielding a more comprehensive picture of the analyzed object. The aim of the proposed project is the first analysis of HCM on a single-cell level. For this research project, I will utilize state-of-the-art singe-cell technologies to study hypertrophic cardiomyopathy, including single-cell transcriptomics, single-cell epigenomics (i.e., single-cell ATAC seq and single-cell DNA methylation analysis), and spatially resolved transcriptomics. This innovative approach is expected to provide a deeper understanding of changes in cellular composition and intercellular interactions in diseased hearts, both in variant positive and unexplained HCM. Furthermore, this will help to elucidate how unexplained HCM cases develop this phenotype. Ultimately, this study will be a further step towards precision medicine for affected patients and towards the identification of novel drug targets.
DFG Programme
WBP Fellowship
International Connection
USA
