Director of Stem Cell Core
530 45th St.
8117 Rangos Research Center
Pittsburgh, Pennsylvania 15201
Heart is a complicated organ with three-dimensional (3D) organization of cellular and extracellular matrix (ECM) essential for blood pumping. Human heart is composed of various kinds of cells, of which cardiomyocytes (CMs), smooth muscle cells (SMCs), endothelial cells (ECs) and cardiac fibroblasts (CFs) are major cell types. CMs provide the contraction power of myocardium. SMCs and ECs form the vasculatures and ECs contribute to the heart valve and endocardium. CFs regulate heart formation and functions, such as electrical transduction and contraction. Damages or death of heart cells due to environmental factors, genetic defects and/or other diseases could lead to human heart diseases. In the United States, heart disease is the leading death factor. Myocardial infarction (MI) affects over 80 million American people and approximately 5 million Americans are living with heart failure. About 50,000 people die each year due to the limited donor hearts for transplant. Additionally, over 50% of patients with heart disease do not respond to current pharmacological administration. Thus the future treatment of heart disease requires a deep understanding of disease mechanisms for mining novel therapeutic targets, as well as the development of personalized therapeutic strategies, such as disease-specific pharmacological reagents and patient-specific cardiac tissues or even whole bio-artificial hearts for transplantation.
To conduct the translational study of human heart disease, my laboratory utilizes a combination of human embryonic stem (ES) cells, human induced pluripotent stem (iPS) cells, tissue engineering and mouse genetic models to address early stage human heart development, human inherited cardiovascular diseases and heart disease therapy. Our research is focusing on the following three directions.
1) Dissecting early human heart formation using human pluripotent stem cells.
We are interested in uncovering novel regulators, such as microRNAs, during early human heart development. This study is utilizing human ES& iPS cells to recapitulate early events in human heart development, and establishing a valuable model system to understand early formation of human cardiovascular progenitors and commitment of human cardiovascular lineage cells. Mouse genetic models will be used to validate findings from human ES cell studies.
2) Modeling human inherited heart diseases using patient-specific iPS cells.
We will generate cardiomyocytes from iPS cells derived from patients with various inherited cardiovascular diseases, and use this unique system to elucidate the cellular and molecular mechanisms of human heart diseases, as well as to establish an in vitro assay for screening therapeutic compounds.
3) Engineering patient-specific heart tissues and whole heart constructs using human iPS cells.
We use human iPS cell-derived Multipotential Cardiovascular Progenitor cells (MCPs) to engineer three dimensional (3D) human heart tissues for studying human early heart development and curing human heart disease. Our long-term goal is to rebuild a whole patient-specific bio-artificial human heart for transplantation.
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