About Us

The central theme of Dr. Hsiai's research program is primarily on hemodynamics and mechanobiology via the application of engineering principles and techniques, including Bio-MEMS and nanotechnology to study oxidative stress and to link physical and chemical properties with vascular biology. Using a micro-fluidic flow model, Dr. Hsiai's lab is investigating the mechanisms whereby hemodynamics regulates the development of coronary artery disease. His group is linking the effects of real-time shear stress on cardiac cell dynamics using intravascular polymer sensors, molecular biology techniques, and proteomics. Using zebrafish heart model, the group is developing micro-ECG for longitudinal monitoring for cardiac arrhythmia. The current research objective is to study vascular inflammatory responses in the context of electrochemical properties and vascular calcification.

Our Projects

Hemodynamics and Cardiac Development Electrical and Mechanical coupling of Zebrafish Hearts
Hemodynamic forces are intimately linked with cardiac development and normal function. Circulating blood imparts fluid shear stress on the walls of the heart during cardiac contractions. Our group is interested in investigating the link between fluid shear stress and cardiac development in a Zebrafish model. In collaboration with Professor Chih-ming Ho, we are acquiring real-time 3D beating heart images using selective plane illumination microscopy (SPIM). This imaging method allows us to determine boundary conditions from image data to prescribe wall motion for computed fluid dynamic (CFD) simulations. In collaboration with Professor Alison Marsden from UCSD, we are assessing hemodynamics and cardiac morphogenesis via the use of moving boundary Computational Hemodynamics (CFD). Our laboratory has been inspired by the developmental biologists for their seminal contributions to cardiovascular medicine using the zebrafish heart model. We and others have developed micro-ECG strategy (Dr. Tai at Caltech) to assess conduction phenotypes in adult and embryonic zebrafish. In collaboration with the zebrafish heart experts, we observed changes in conduction phenotypes in the regenerating myocardium in response to ventricular injury. In collaboration with Dr. K. Kirk Shung, NIH Director of Ultrasonic Transducers Resource Center, we are demonstrating mechanical phenotypes in terms of ventricular compliance (E- and A- waves) with high spatial and temporal resolution. In collaboration with zebrafish experts, Dr. Ellen Lien at Los Angeles Children's Hospital, Dr. Jau Chen at UCLA, Dr. Xiaolei Xu at Mayo Clinic, and Dr. Neil C. Chi at UCSD, we are assessing the biomechanical mechanisms underlying the functional/physiological phenotypes in the regenerating myocardium by incorporating microelectrode arrays and high frequency ultrasonic transducers, histology and optical voltage mapping conduction. These fundamental findings will pave the way for early detection, monitoring, and management of aberrant electrical signals in neonatal models of tissue regeneration.




Vascualr Repair Related in Shear Stress and Oxidative Stress Urban Air Pollutants Ultrafine Particles and Vascular Biology
Wnt-Ang-2 signaling and vascular endothelial repair. The tails of transgenic Tg (kdrl:GFP) zebrafish embryos were amputated at 72 hpf . At 0 day post amputation (dpa), the red arrow pointed to the site of injury. At 1 dpa, initiation of endothelial repairs was present. At 3 dpa, complete tail repair was observed, as indicated by the yellow arrow. Chronic exposure to ambient urban ultrafine particles (UFP, dp < 150 nm) is an emerging environmental risk factor associated with increased morbidity and mortality. This issue is particular relevant in large cities that rely on automotive transportation such as Los Angeles. In a collaborative effort with Professors Constantinos Sioutas and Professor Celeb Finch from USC and Professors Mohamad Navab, Jesus Araujo, Linda Demer, and Prof. Yin Tintut from the UCLA School of Medicine, we are assessing the molecular mechanisms underlying multi-organ system effects in response to ambient air pollutant exposure. Our collaborations have culminated in novel signal pathways leading to endothelial cell dysfunction and CVC cell calcification, as well as lipid peroxidation and reduced HDL anti-oxidant capacity in the LDLR-null mouse model.
Integrated intravascular sensors to assess unstable plaque Hemodynamics & Mechanobiology of Endothelium
Our group have developed the first quantitative micro-technological approach to measure in real-time changes in intravascular shear stress in the New Zealand White rabbits and swine models. We have further applied microelectromechanical systems (MEMS) and nano-scale sensors for real-time quantification of shear stress and oxidative stress with pathological significance to the initiation of inflammatory resposnes. Our micro-enabled technology (e.g., MEMS shears stress sensors and concentric bipolar microelectrodes), molecular tools (e.g., adenoviruses to over-express Mn-SOD, small interference RNAs, flow cytometry to measure mitochondrial redox status), as well as transgenic and knockout animals Our group has demonstrated the first quantitative approach to changes in intravascular shear stress (ISS) with vascularnulloxidative stress in New Zealand White (NZW) rabbit and swine models. We have demonstrated that spatial (/x) and temporal (/t) variations in shear stress modulate post-translational oxidative modifications of low density lipoprotein protein (LDL) and mechano-signal transduction of mitochondrial redox states.
Fluorescent light-sheet microscopy to image 3-D zebrafish embryo and beating heart Ultramicroscopy with Super-Resolution and Clearing Techenique
(a) The sample is placed at the intersection of illumination lens (IL) and detection lens (IL) in our LSM system. (b) LSM applies a laser light-sheet to illuminate the sample. The illuminated planes are orthogonally detected by the detection objective. Cyl: cylindrical lens. Deb obj: detection objective. (c) A schematic diagram illustrates a sheet of laser light transverses the embryo. (d) The entire embryo can be imaged at the micron scale within 30 seconds. Inset reveals the trabeculated endocardium. (e) Magnification of the heart reveals the fli-1-eGFP-labeled endocardium and DsRed-labeled red blood cells throughout the cardiac cycle. (f) 4-D LSM image reveals a beating heart. By slicing and applying the super-resolution to increase the image resolution for optically cleared large-scale neonatal mouse hearts (several milimeter scale), followed by volumetric rendering, we demonstrated the use of 4x objective with a numerical aperture of 0.13 to resolve the single cell level of cardiac trabeculation and changes in orientation of myocardial fibers from left ventricle to septum, to right hearts.

Wireless Batteryless Miniature Implantable Cardiac Pacer
Despite great advancements in implantable cardiac pacemaker technology, complications from pacemaker leads continue to compromise nearly 10% of all implants. This has motivated significant research for the development of leadless devices. These include battery-based systems, power harvesting devices, and stimulators wirelessly powered through radiofrequency radiation. Our research is focused on the development of an inductive power transfer system with a remote stimulation control system. Our proposed system is capable of significantly improving power efficiency and reducing tissue energy absorption in a highly asymmetrical system in which the pacer is small enough to be intravascularly deployed and implanted with a stent-like fixation mechanism.