High-Throughput Screening for Novel Drug Discovery Using Patient-Specific Induced Pluripotent Stem Cells for Familial Hypertrophic Cardiomyopathy

Abstract

The objective of this proposal is to discover novel drugs to treat hypertrophic cardiomyopathy (HCM) using cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs). HCM is one of the most prevalent heritable heart diseases in the world, affecting about 1 out of 500 people, including military families. It is characterized by a thickening of the heart tissue, reduced cavity size, impaired relaxation time, arrhythmias and ultimately sudden cardiac death (SCD). Here, we have validated two candidates of drugs that lead to inhibit calcineurin/NFAT or Mitigating enhanced actomyosin crossbridge formation in patient derived hiPSC-CMs. Additionally, we performed transcriptome analysis by RNA sequencing (RNAseq) with the control, isogenic MYH7-corrected, isogenic MLP-corrected and proband MLP-W4R;MYH7-R723C iPSC-CMs to elucidate the mechanism of pathological hypertrophy.

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Document Details

Document Type
Technical Report
Publication Date
Jan 01, 2022
Accession Number
AD1167699

Entities

People

  • Jin‐Kyu Park

Organizations

  • Yale University

Tags

DTIC Thesaurus Topics

  • Abstracts
  • Biomedical Research
  • Cardiomyopathies
  • Cells
  • Department Of Defense
  • Diseases And Disorders
  • Enzyme Inhibitors
  • Gene Expression
  • Genes
  • Genetics
  • Heart Diseases
  • Hypertrophy
  • Maryland
  • Medical Personnel
  • Military Families
  • Molecules
  • Relaxation Time
  • Rna Sequence Analysis
  • Small Molecules
  • Stem Cells
  • Students
  • Throughput

Fields of Study

  • Biology
  • Medicine

Readers

  • Cardiovascular Physiology
  • Molecular and Cellular Biology

Technology Areas

  • Biotechnology