Stem Cell Center, Yale: Tissue Specific Stem Cells
My research laboratory seeks to understand the basic biology of a novel population of cardiovascular progenitor cells (CPC) that can produce the majority of heart and blood vessel cells in the heart. We are using these CPC cells to generate 3D cardiac tissue in order to repair the injured heart using animal models. We are also reprogramming skin cells from patients with cardiovascular diseases into pluripotent stem cells and then redifferentiate these pluripotent stem cells into mature cardiovascular cells. In this way, we will be able to derive unlimited amount of cardiovascular cells with disease-causing mutations and study cardiovascular disease mechanisms. Furthermore, we are pursuing to correct the disease-causing phenotype by genetic repair as well as initiating small molecule screening.
Extensive Research Description
My research laboratory seeks to understand the basic biology of a novel population of cardiovascular progenitor cells (CPC) derived from heart tissues and embryonic stem (ES) and induced pluripotent stem (iPS) cells. These CPC are capable of making nearly an entire heart during heart formation and are marked by Isl1, a LIM-Homeo domain transcription factor. Through a high-throughput small molecule screen coupled with murine ES cell and embryonic heart developmental studies, we have successfully discovered several small molecules modulating these CPC. One of our major goals is to further dissect the mechanisms governing the biology of these CPC. We believe that knowledge from these studies will enable us to enhance activities of adult CPC in the injured heart in vivo to ameliorate heart diseases.
Adult stem cells may undergo aging, possibly affecting their ability to maintain organ homeostasis. Therefore, our second research project is to obtain functional CPC and cardiomyocytes from human ES and iPS cells for cell-based therapy. In collaboration with Dr. Christopher Breuer’s laboratory at Yale, we will utilize bio-degradable scaffold to establish engineered heart tissues (EHT) with CPC and examine their contribution to heart repair and regeneration in animal models.
With purified CPC and cardiomyocytes from human ES and iPS, our third research project is to establish an in vitro cellular model to study human heart development and disease mechanisms by investigating the effect of genetic alterations on the functions of CPC and cardiomyocytes.
Lastly, we would like to take advantage of our previous experience in high-throughput small molecule screening to establish assays for new chemical screens to directly reprogram heart fibroblast (scar-forming cells) and quiescent adult epicardial cells into CPC, essential for heart repair and regeneration. By modulating adult resident CPC directly in vivo, and exploring cell-based therapy coupled with tissue engineering in vitro, we believe that our lab represents an exciting time on the forefront of heart repair and regeneration studies. We wholeheartedly welcome you to join our team and contribute to such exciting endeavors.1. Isolate cardiovascular progenitor and fundtional cardiomycoytes from human ES and iPS cells, genearte engineered heart tissues with these heart cells, and test their functions in injured animal heart.
2. Generate patient-specific iPS cells using Cre-loxp-based transgene-free and modified mRNA strategies, derive heart cells from iPS cells, and study heart disease pathogenesis and mechanisms using 2D and 3D in vitro model.
3. Study self-renewal and cardiac differentiation of cardiovascular progenitor cells using murine embryonic heart and transgenic models.
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