Dr. Huang's laboratory aims to understand the chemical and mechanical interactions between extracellular matrix (ECM) proteins and pluripotent stem cells that regulate vascular and myogenic function. The fundamental insights of cell-matrix interactions are applied towards stem cell-based therapies with respect to improving cell survival and regenerative capacity, as well as engineered vascularized tissues for therapeutic transplantation. Current projects focus on various aspects of mechanical and physical factors on tissue regeneration. Examples include:
1) Cellular Biomechanics for in High Through Chemical Screening: To develop new technology for high-throughput quantitative assessment of vascular endothelial cell biomechanics for cardiovascular drug screening. We hypothesize that cellular biomechanics can be a predictive biomarker of endothelial health.
2) Engineered Matrix Microarrays to Enhance the Regenerative Potential of iPSC-Derived Endothelial Cells: We propose to develop a combinatorial family of engineered ECMs (eECMs) with independently tunable biochemical and biomechanical cues, including stiffness and stress relaxation rate for high-throughput, matrix array studies of induced pluripotent stem cell-derived endothelial cell (iPSC-EC) survival and angiogenic potential. The optimally designed eECMs will then be coinjected with iPSC-EC for treatment of peripheral arterial disease in a mouse model of hindlimb ischemia (Sponsor: NIH).
3) iPSC-Derived Smooth Muscle Progenitors for Treatment of Abdominal Aortic Aneurysm: We propose to deliver human induced pluripotent stem cell-derived smooth muscle progenitors to the site of abdominal aortic aneurysm will replenish smooth muscle cells, enhance elastin production, and abrogate wall dilatation in a murine model (Sponsor: CIRM).
4) Vascularized Cardiac Patch with Physiological Orientation for Myocardial Repair: The aims are to engineer a vascularized aligned iPSC-derived CM (cardiomyocyte) patch and elucidating the molecular mechanisms of ECM-mediated nitric oxide signaling in enhancing iPSC-CM survival and phenotype; and to determine the therapeutic effect of a vascularized aligned iPSC-derived CM patch for treatment of myocardial infarction (Sponsor: Dept of Veteran Affairs).
5) Other ongoing research areas: mRNA-based therapeutics, exosome biologics, microgravity effects on tissue regeneration and dysfunction, 3D bioprinting of engineered skeletal muscle, viscoelasticity effects on endothelial-to-mesenchymal transition, electro-osmosis for treatment of lymphedema, tissue chips for stem cell manufacturing
Dr. Huang's laboratory research is funded by the National Institues of Health, Department of Defense, California Institute for Regenerative Medicine, National Science Foundation, and the Department of Veteran Affairs.