We desire and enable achieving cardiovascular precision medicine by leveraging patient-specific clinical data and hiPSC-derived cells/organoids.
Fluorescent reporters have been widely applied in biomedical research given their easy observation under the microscope. Our recent work by generating a dual reporter platform in hiPSCs has shown the robustness of fluorescent reporters used for delineating cardiac lineages and isolating lineage-specific cardiovascular cells. The work facilitates understanding of cardiac lineage determination during in vitro differentiation and further application of lineage-specific cardiovascular cells in precise disease modeling and drug testing. We aim to further apply different fluorescent reporter platforms coupled with advanced live-cell imaging modalities, CRISPR screening, and multi-omics techniques to 1) better understand cell fate determination which accelerates the process of directed differentiation in vitro; 2) delineate the genetic significance in the efficacy and toxicity of drugs.
The heart is a complex organ composed of several cell types. Studies have shown that interactions between cardiomyocytes and other cells play an important role in maintaining the homeostasis of the heart and remodeling of the heart under pathological conditions. One of the ongoing projects is to decipher the mechanisms underlying cardiac fibrosis in hypertrophic cardiomyopathy. We are also actively exploring the cross-talk between cardiomyocytes and other cell types using state-of-the-art technologies to better understand how different cell types contribute to the development of heart diseases. The overarching goal is to understand the heart disease mechanisms in a more precise manner and eventually lead to tailored therapeutic regimens.
High throughput screening studies
Action potential, calcium handling, and contractility are three key parameters of cardiomyocyte function. Our previous work has demonstrated that by monitoring the three parameters of hiPSC-CMs, we enable to determine the drug-induced cardiac toxicity, one of the main causes of post-market withdrawal of medical drugs. In this ongoing work, we aim to leverage the high throughput screen platform of hiPSC-CMs/mico-tissues by simultaneously measuring action potential, calcium events, and contractility to determine the drug toxicity. We aim to develop a machine-learning-based analysis algorithm to objectively detect abnormality of cardiomyocyte function. We are actively collaborating with drug development teams for drug screening. The overarching goal is to improve drug testing accuracy, understand drug toxic mechanisms, and accelerate the process of drug discovery.
One of the goals of our lab is to continuously train talented young scientists. We are here to help you fulfill your career goal. We are very happy to discuss your research interests and career goal, so we can tailor a specific project that helps you to achieve your goal and is also in line with our lab's research interests.