Stanford Cardiovascular Institute
My long-term goal is pursuing precision medicine to treat cardiovascular diseases (CVDs). The optimized and personalized therapies on CVDs are significant and advanced to achieve the ultimate cure in comparison to the conventional treatments. My academic training and research experiences ideally pave a clear way through strengthening the background in tissue engineering, biofabrication, polymer science, and stem cell biology & therapy, leading myself into the field of precision medicine. As an undergraduate, I started to get exposed to the interdisciplinary idea of applying polymer chemistry and microbiology into looking for an advanced solution to bacterial corrosion in the oil field. As a graduate student, I went further to explore the novel applications of synthetic biopolymers and natural proteins into scaffold fabrication for seeking possibilities of cardiovascular repair & regeneration. In this study, I have obtained expertise in chemistry and physics of biopolymer, and cardiovascular tissue engineering. In the doctoral period, I was trained inclusively on cardiac physiology, stem cell biology, tissue engineering, microfabrication and live-cell imaging to study the ECM involved sarcomerogenesis and electrophysiology of single cardiomyocytes. Then, the mechanisms of stem cell therapy on cardiac regeneration and protection through intercellular interactions were studied in a microfluidic-based biochip in high throughput, which is one of the powerful tools for building in vitro models for drug screening and discover in the regenerative medicine. A 3D in vitro model for studying remodeling of hypertrophied myocardium was also designed and fabricated. A uniaxial single-cell stretcher with elastic microgrooves was used to the culture, and preload cardiomyocyte at 6 ~ 10%, then the in situ observation of myofibril remodeling was imaged with a secondary harmonic confocal microscope. From this study, I learned how the microenvironmental factors, such as blood pressure, strain/stress, and drugs, lead to congestive cardiac diseases and heart failure. Those factors should be fully considered in the applications of precision medicine. As the foundation of precision medicine, induced pluripotent stem cell (iPSC) and its derived cardiovascular cells (cardiomyocytes, CM and endothelial cells, ECs) from patients have been extensively utilized to model the human cardiovascular diseases for pathological mechanism and therapeutic targets of treatment. Under this certain circumstance, I started to realize the importance and innovation of combining the hiPSC and tissue engineering to advance the study and translation of precision medicine. At Stanford as a postdoctoral researcher since 2015, I can make this happen with great support from tremendous research and collaboration resources at the cardiovascular institute. I have applied the advanced microfabrication techniques, such as micropatterning and 3D engineered heart tissue, genome editing, and hypertrophy cardiomyopathy (HCM) patient iPSC-derived cardiovascular cells, to model HCM in a dish with 2D micropatterned adult-like CMs and 3D engineered heart tissue. Finally, gene therapy with novel targets and robust in vivo delivery approaches have been applied for the possibilities of cardiovascular regenerative medicine.
Molecular and functional resemblance of differentiated cells derived from isogenic human iPSCs and SCNT-derived ESCs.
Proceedings of the National Academy of Sciences of the United States of America 12, 2017 | Pubmed ID: 29203658
Comparison of Non-human Primate versus Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Treatment of Myocardial Infarction.
Stem cell reports 02, 2018 | Pubmed ID: 29398480
Progress, obstacles, and limitations in the use of stem cells in organ-on-a-chip models.
Advanced drug delivery reviews 02, 2019 | Pubmed ID: 29885330
A Premature Termination Codon Mutation in MYBPC3 Causes Hypertrophic Cardiomyopathy via Chronic Activation of Nonsense-Mediated Decay.
Circulation 02, 2019 | Pubmed ID: 30586709
An miRNA Delivery System for Restoring Infarcted Myocardium.
ACS nano 09, 2019 | Pubmed ID: 31149806
Modelling diastolic dysfunction in induced pluripotent stem cell-derived cardiomyocytes from hypertrophic cardiomyopathy patients.
European heart journal Dec, 2019 | Pubmed ID: 31219556
Soah Lee*,1,2,3,
Huaxiao Yang*,1,2,3,
Caressa Chen*,1,2,3,
Sneha Venkatraman1,2,3,
Adrija Darsha1,2,3,
Sean M. Wu1,2,3,
Joseph C. Wu1,2,3,
Timon Seeger1,2,3,4,5
1Stanford Cardiovascular Institute, Stanford University School of Medicine,
2Department of Medicine, Division of Cardiovascular Medicine, Stanford University,
3Institute for Stem Cell Biology and Regenerative Medicine, Stanford University,
4Department of Medicine III, University Hospital Heidelberg,
5German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim