Yibing Qyang, PhD

Associate Professor of Medicine (Cardiology) and of Pathology; Section of Cardiovascular Medicine

Research Departments & Organizations

Internal Medicine: Cardiovascular Medicine: Qyang Lab


Vascular Biology and Therapeutics Program

Yale Stem Cell Center

Office of Cooperative Research

Research Interests

Cardiology; Cardiovascular Diseases; Heart; Physiology; Stem Cells; Tissue Engineering

Research Summary

Our research laboratory has been focused on establishing novel cellular and animal models of human cardiovascular diseases for the purpose of elucidating causative mechanisms and identifying potential therapeutic interventions to treat those diseases. Through a close collaboration with several clinicians at Yale, we are able to obtain cells from a variety of tissues procured from healthy subjects and patients with cardiovascular diseases. These cells include dermal fibroblast cells derived from skin punch biopsies or peripheral mononuclear blood cells, which are isolated and reprogrammed into induced pluripotent stem (iPS) cells by introducing stem cell factors before being re-differentiated into functional cardiovascular cells. In this way, we have the ability to derive an unlimited amount of human cardiovascular cells for use in our investigations into the specifics of cardiovascular disease mechanisms and the discovery of potential therapeutic treatments by performing high-throughput drug screening, as well as the generation of patient-specific, autologous cardiovascular tissues for organ repair.

Specialized Terms: Heart; Stem cell; ES cell; iPS cell; Physiology; Tissue engineering; Small molecule; Patient; Disease; Cardiovascular

Extensive Research Description

Our research laboratory has been focused on establishing novel cellular and animal models of human cardiovascular diseases for the purpose of elucidating causative mechanisms and identifying potential therapeutic interventions to treat those diseases. Our research covers the following areas:

1. Vascular disease mechanism and drug screening: Having patient-specific vascular smooth muscle cells (SMCs) available facilitates the study of disease and development of novel therapeutic interventions. We were the first to describe the development of a human induced pluripotent stem cell (iPSC) line from a patient with supravalvular aortic stenosis (SVAS). SVAS iPSC-SMCs recapitulate key pathological features of patients with SVAS and provide a promising strategy to study disease mechanisms and to develop novel therapies. The objectives of our recently funded Connecticut Regenerative Medicine Research Program (2015-2019) are to obtain mechanistic insight into how elastin and candidate drug vinblastine inhibit the hyperproliferation of SVAS iPSC-SMCs and to screen for additional small molecules that ameliorate the hyperproliferative defect in SVAS. By studying SVAS, a particular disease with an intrinsic defect in SMC proliferation, we may gain insights into the disease mechanisms and develop novel therapies for multiple vascular proliferative diseases. Rotation students are welcome to join this project and learn vascular disease mechanism and drug screening using patient stem cell modeling.

2. Vascular tissue engineering and repair: The availability of unlimited supply of iPSC-derived SMCs and endothelial cells (ECs) has also allowed for the generation of 3D vascular tissue for disease studies and blood vessel repair (awarded NIH R01 program 2013-2018). We have engineered 3D tissue rings from hiPSC-SMCs using a facile one-step self-assembly technique in collaboration with Dr. Marsha Rolle group. The tissue rings are mechanically robust and can be used for vascular tissue engineering, disease modeling and drug screening.

Furthermore, we have generated a biological blood vessel by seeding hiPSC-SMCs onto biodegradable polyglycolic acid (PGA) scaffold in bioreactors in collaboration with Dr. Laura Niklason group. These engineered vessels remained mechanically intact and patent after implanted into nude rats as abdominal aorta interposition grafts. This research paves the foundation for developing autologous grafts for clinical intervention in patients with vascular diseases. Future studies will be performed to further enhance the mechanical properties of the engineered vessels and to test the long-term durability of these vessels in vivo.

3. Cardiac disease modeling and mechanism: Human iPSC potentially provide a unique resource for generating patient-specific cardiomyocytes to study cardiac disease mechanisms and treatments. We were the first group to report that small molecule Wnt inhibitors IWP1 or IWP4-based, highly efficient production of functional cardiomyocytes from embryonic stem cells (ESCs) or iPSCs. We have used iPSC approach to study the functional consequences of sarcomeric and stretch-sensing mutations in hypertrophic cardiomyopathy (HCM; thickening of the heart tissue, affecting 1 out of 500 people). We have recently derived iPSCs from patients with MYH7(sarcomeric) and MLP (stretch-sensing) mutations. We will investigate the disease mechanism by producing engineered heart tissue constructs (EHTs) that can be precisely stretched in vitro in collaboration with Dr. Stuart Campbell group. This project is supported by an awarded NIH R01 program (2016-2020). Rotation students can join this project, gain experience in studying cardiac disease mechanism, and learn how to design potential drug screening approach to rescue/treat this devastating heart disease.

4. Cardiac repair and regeneration based on cardiac progenitor cells: We have also established robust cardiac differentiation approach in human ESCs and iPSCs to derive ISL1+ cardiovascular progenitor cells (ISL1-CPCs), a CPC population representative of an authentic cardiac origin, for cardiac repair. We show that ISL1-CPCs have important physiological effects to improve heart contractile function, reduce scar size and increase blood vessel formation in the mouse model. Thus, our findings indicate that the ISL1-CPC approach may represent a significant advance in the heart repair field. Future efforts will be made to translate ISL1-CPC heart repair from mouse to large animal models. This project is supported by a Department of Defense Award (another grant is pending and other proposals are in preparation). Rotation students joining this project will learn how to isolate ISL1-CPCs from human ESCs and iPSCs, generate cardiac progenitor-based tissue, and gain experience in cardiac repair and regeneration.

5. Preclinical modeling of cardiovascular repair and regeneration: We have generated robust iPSC lines from pigs for preclinical studies.The availability of pig iPSC will enable us to engineer cardiovascular tissues and then test in pigs, which closely mimic human cardiovascular physiology. Our studies will provide critical preclinical knowledge for the application of autologous stem cell-based cardiovascular repair and regeneration therapies.

Selected Publications

See list of PubMed publications

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