Yang Lab

The research laboratory of Lei Yang, PhD, focuses on human-specific heart development, disease and regeneration.  The main approaches utilized in the Yang Lab are human embryonic stem (ES) cells, human induced pluripotent stem (iPS) cells, tissue engineering and mouse genetic models.

The heart is a complicated organ with three-dimensional organization of cellular components and an extracellular matrix (ECM) essential for pumping blood. A human heart is composed of various kinds of cells, including the major cell types of cardiomyocytes (CMs), smooth muscle cells (SMCs), endothelial cells (ECs) and cardiac fibroblasts (CFs). Throughout the past few decades, studies of heart development have been mainly focused on conserved gene regulatory mechanisms, which control various aspects of cardiogenesis across multiple species from drosophila to mice.

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Despite the high evolutionary conservation of cardiogenesis, the human heart exhibits unique properties, including distinctive morphogenesis and electrophysiological properties. These species-specific differences suggest the existence of novel genetic or epigenetic programs in each species. However, the mechanisms that regulate unique aspects of human cardiogenesis are largely unknown. Damage or death of heart cells due to environmental factors, genetic defects and/or other diseases could lead to human heart disease.

In the United States, heart disease is the leading cause of death. Myocardial infarction (MI) affects more than 80 million American people and approximately 5 million are living with heart failure. A limited supply of donor hearts for transplant leads to about 50,000 deaths each year. Thus heart disease therapy requires a deep understanding of disease mechanisms for finding novel therapeutic targets as well as development of personalized therapeutic strategies, such as disease-specific drugs and patient-specific heart tissues or whole organ transplantation.

Active Research

Dissecting early heart development using human pluripotent stem cells

The Yang Lab is interested in uncovering novel regulators, such as non-coding RNAs, during early human heart development. This study utilizes human ES & iPS cells to recapitulate early events in human heart development and establish 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. 

Studying inherited heart diseases using patient-specific iPS cells

The research group within the Yang Lab generates cardiomyocytes from iPS cells derived from patients with various inherited cardiovascular diseases. The group uses this unique system to elucidate the cellular and molecular mechanisms of human heart diseases and to establish an in vitro assay for screening therapeutic compounds. 

Engineering patient-specific heart tissues and constructs using human iPS cells

The Yang Lab uses human iPS cell-derived multipotential cardiovascular progenitor cells (MCPs) to engineer 3D human heart tissues for studying early heart development and curing human heart disease. Its long-term goal is to rebuild a whole patient-specific bio-artificial human heart for transplantation. 

Media Coverage of the Yang Lab

In 2014, the Yang Lab generated nationwide attention for a breakthrough study, published by Nature Communications. The study successfully reconstructed a decellularized mouse heart, which began to beat on its own again.

Using induced pluripotent stem (iPS) cell technology, Dr. Yang and his team reprogrammed human skin cells to become multipotential cardiovascular progenitor (MCP) cells. These cells regenerated the organ and restored some of its function.

The study shows tremendous promise for organ engineering and regeneration for the thousands of patients who are waiting for a heart.

Research Funding

  • 2014 NIH Directors New Innovator Award 1DP2HL127727-01
    Role: PI

    Title: Toward regeneration of whole bioartificial human heart

  • 2017 American Heart Association AHA Grant in Aid 17GRNT33440059
    Role: PI

    Title: miRNA126 regulates human heart development

  • 2017 American Heart Association AHA Postdoctoral Fellowship 17POST33460140
    Role:  Mentor

    PI: Juli Liu

    Title: LncRNA HBL1 regulates human cardiomyocyte development

  • 2019 American Heart Association AHA Postdoctoral Fellowship
    19POST34380871

    Role: PI

  • 2019 American Heart Association AHA Transformative Priject Award
    19TPA34850038

    Role: PI

  • 2019 NHLBI R01 HL 147871
    Transcriptional Factor SOX2, LNCRNA, HBL1. MicroRNA1 and PRC2 Epigenetic Complex Compose a Network to Orchestrate Cardiac Differentiation From Human Pluripotent Stem Cells

    Role: PI

  • 2019 NICHD R21 HD095049
    Identification of Novel Human LNCRNAs Controlling Human Cardiogenesis

    Role: PI

Recent Publications

Visit PubMed to find a full list of Yang’s publications.
  • 2018

    Liu JL, Li Y, Lin B, Sheng Y, Yang L. HBL1 Is a Human Long Noncoding RNA that Modulates Cardiomyocyte Development from Pluripotent Stem Cells by Counteracting MIR1. 2017. Developmental Cell. 2017. 42: 333-348. Online on August 21th.

  • 2017

    Liu JL, Li Y, Lin B, Sheng Y, Yang L. HBL1 Is a Human Long Noncoding RNA that Modulates Cardiomyocyte Development from Pluripotent Stem Cells by Counteracting MIR1. 2017. Developmental Cell. 2017. 42: 333-348. Online on August 21th.

  • 2015

    Li Y, Lin B, Yang L. Comparative Transcriptomic Analysis of Multiple Cardiovascular Fates from Embryonic Stem Cells Predicts Novel Regulators in Human Cardiogenesis. Scientific Reports. 2015. 5:09758.

    Lin B, Li Y, Han L, Kaplan AD, AO Y, Kalra S, Bett G, Rasmusson RL, Denning C, Yang L. Modeling and study of the mechanism of dilated cardiomyopathy using induced pluripotent stem cells derived from individuals with Duchenne muscular dystrophy. Disease Models & Mechanisms. 2015. 8:457-466.

  • 2013

    Lu TY, Lin B, Kim J, Sullivan M, Tobita K, Salama G, Yang L. Repopulation of Decellularized Mouse Heart with Human Induced Pluripotent Stem Cell Derived Cardiovascular Progenitor Cells. Nature Communications. August, 2013. 4, Article number: 2307.

  • 2008

    Yang L, Soonpaa M, Edler E, Roepke T, Kattman S, Kennedy M, Henckaerts E, Bonham K, Abbott G, Lindon M, Field L and Keller G. Human cardiovascular progenitors develop from a KDR+ ES cell-derived population. Nature. 2008, 453: 524-528.

Research Team

Lei Yang, PhD

Associate Professor of Pediatrics

Juli Liu

Assistant Research Professor of Pediatrics

Lei Han

Postdoctoral Fellow in Pediatrics