Location

IRC (Library)

Advisor(s)

Dr Chrishan Ramachandra

Start Date

30-6-2018 10:00 AM

End Date

30-6-2018 10:15 AM

Abstract

Hypertrophic cardiomyopathy (HCM), that clinically manifests as an enlarged heart is a highly prevalent cardiac disorder with propensity towards arrhythmia-induced sudden cardiac death. The mechanism of HCM remains poorly defined, necessitating further understanding of the disease for improved therapeutic strategies. As it is challenging to obtain cardiac biopsies from human subjects, using induced pluripotent stem cells technology, we generated cardiomyocytes (CMs) in a dish from HCM patients. These HCM-CMs presented the clinical manifestation in that they were significantly larger in size in comparison to control (healthy)-CMs. Furthermore, gene expression profiling of cardiac ion channels revealed increased transcripts encoding for calcium channels which resulted in calcium-mediated arrhythmias in the HCM-CMs. Our humanized HCM model recapitulated the disease phenotype and the subsequent findings lay the foundation for gaining significant insight into disease pathology for therapeutic intervention.

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Jun 30th, 10:00 AM Jun 30th, 10:15 AM

A humanized hypertrophic cardiomyopathy model to elucidate molecular mechanism in disease pathology

IRC (Library)

Hypertrophic cardiomyopathy (HCM), that clinically manifests as an enlarged heart is a highly prevalent cardiac disorder with propensity towards arrhythmia-induced sudden cardiac death. The mechanism of HCM remains poorly defined, necessitating further understanding of the disease for improved therapeutic strategies. As it is challenging to obtain cardiac biopsies from human subjects, using induced pluripotent stem cells technology, we generated cardiomyocytes (CMs) in a dish from HCM patients. These HCM-CMs presented the clinical manifestation in that they were significantly larger in size in comparison to control (healthy)-CMs. Furthermore, gene expression profiling of cardiac ion channels revealed increased transcripts encoding for calcium channels which resulted in calcium-mediated arrhythmias in the HCM-CMs. Our humanized HCM model recapitulated the disease phenotype and the subsequent findings lay the foundation for gaining significant insight into disease pathology for therapeutic intervention.

 

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