Lecture
Proteomics and Precision Medicine and The Potential Route to Individualize Therapeutics
- at -
- ICM Saal 2
- Type: Lecture
Lecture description
Precision medicine leverages an individual's Omic signature, including the proteome, for personalized diagnosis and treatment. In cardiac research, proteomics reveals unique disease mechanisms even in patients with identical diagnoses, often lacking clear
therapeutic options. To address this, we developed a high-throughput proteomics platform using human iPSC-derived cardiomyocytes for drug screening across diverse genetic backgrounds. Single-cell proteomics confirmed these cells mimic adult heart
cardiomyocytes, forming distinct proteome clusters based on metabolic and myofilament protein expression. Notably, these cardiomyocytes express a wide variety of unexpected proteins (not known to be present in the adult cardiomyocytes), indicating
proteome flexibility at the single-cell level. Interestingly, initial findings suggest individual cardiomyocytes' drug responses vary based on unique proteomes, impacting patientspecific therapeutic outcomes. In hypertrophic cardiomyopathy, a single amino acid
mutation in a myofilament protein showed that the extensive proteome heterogeneity was influenced by mutant protein dosage. This may explain how identical mutations lead to diverse cardiac pathologies. We will discuss how insights from single-cell
proteomics can help understand heart disease and, similarly, neurological diseases impacting the strategy for development of personalized therapeutics.
therapeutic options. To address this, we developed a high-throughput proteomics platform using human iPSC-derived cardiomyocytes for drug screening across diverse genetic backgrounds. Single-cell proteomics confirmed these cells mimic adult heart
cardiomyocytes, forming distinct proteome clusters based on metabolic and myofilament protein expression. Notably, these cardiomyocytes express a wide variety of unexpected proteins (not known to be present in the adult cardiomyocytes), indicating
proteome flexibility at the single-cell level. Interestingly, initial findings suggest individual cardiomyocytes' drug responses vary based on unique proteomes, impacting patientspecific therapeutic outcomes. In hypertrophic cardiomyopathy, a single amino acid
mutation in a myofilament protein showed that the extensive proteome heterogeneity was influenced by mutant protein dosage. This may explain how identical mutations lead to diverse cardiac pathologies. We will discuss how insights from single-cell
proteomics can help understand heart disease and, similarly, neurological diseases impacting the strategy for development of personalized therapeutics.
