- Assistant Professor of Cardiothoracic Surgery
Stanford Cardiovascular Institute
- Principal Investigator, Center for Tissue Regeneration, Repair and Restoration; Veterans Affairs Palo Alto Health Care System
- 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 differentiation. 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 implantation. Current projects focus on the role of naturally-derived ECMs to enhance endothelial differentiation of induced pluripotent stem cells on two-dimensional ECM microarrays of varying substrate rigidity. The knowledge gained from understanding cell-ECM interactions are applied towards engineering prevascularized skeletal or cardiac muscle constructs using nanotopographical cues derived from nanofibrillar ECMs.
Mahdis Shayan, PhD
PhD in Industrial Engineering, University of Pittsburgh
Peripheral arterial disease (PAD) is a highly prevalent pathological condition which results in critical limb ischemia. Lack of effective therapeutic approaches to restore the blood flow in response to ischemia, would lead to limb amputation and death. Stem cells have displayed a great potential for vascular regeneration in treating vascular and ischemic diseases. Endothelial cells (ECs) derived from human induced pluripotent stem cells (iPSCs) are promising patient-specific cell sources to restore blood perfusion. The aim of my research is to understand how biochemical and biomechanical cues of microenvironmental combinatorial engineered extracellular matrices (e-ECMs) contribute to angiogenic potential of iPSC-ECs. The optimized e-ECMs condition would enhance the survival and angiogenic function of iPSC-ECs and can be used for efficient transplantation of the cells. The findings of this study would help develop a new strategy based on iPSC-ECs to enhance angiogenesis and treat PAD.
- PhD, Biomedical Engineering, University of California, Davis
- BS, Bioengineering, University of California, San Diego
- Cardiovascular disease is the leading cause of death for both men and women in the United States, with over 1 million deaths annually. Limited suitability of the saphenous vein required for conventional grafts used to treat patients with cardiovascular diseases, as well as issues of thrombosis and restenosis associated with prosthetic alternatives drives the need for alternative vascular grafts. Therefore, we are exploring the generation and characterization of an aligned three-dimensional vascular graft that will direct the longitudinal orientation of human iPSC-EC to provide instructive cues that may prevent graft stenosis, thereby providing a viable vascular graft with long-term patency and clinical relevance. Another interesting concept is the ability of substrate stiffness to mediate differentiation of cells along different lineages in response to the biomechanical interactions with the surrounding matrix environment. We are examining the role of substrate rigidity on modulation of endothelial cell growth, morphology, senescence, endothelial-mesenchymal transformation, and generation.
- PhD, Chemical and Biomolecular Engineering, Johns Hopkins University
- BSc, Chemical Engineering, University of Delaware
- Coronary heart disease (CHD) is characterized by narrowing of the coronary arteries that supply blood flow to the heart which leads to myocardial infarction (MI) and ultimately heart failure. Cell-based therapy using induced pluripotent stem cells (iPSCs) provides a potentially useful therapy to combat CHD, a disease that affects over 15 million people. Current cardiac cell based therapies lack the highly organized physiological structure with ordered cellular alignments and gap junctions of cardiomyoctyes which ultimately drives efficient electromechanical coupling and contractility. My work focuses on engineering a three-dimensional vascularized cardiac patch with pre-formed physiological cellular organization composed of induced pluripotent stem cell derived cardiomyocytes and endothelial cells. We are investigating whether a three-dimensionally aligned iPSC-derived cardiac patch with endothelial interactions will provide superior therapeutic capacity because of enhanced cell survival and cardiac function, due to more effective electrical coupling and organized tissue morphology.
- PhD, Mechanical Engineering, National University of Singapore (NUS), Singapore
- Traumatic injuries, surgical procedures, or diseases may impair revascularization capacity of skeletal muscle. In a large number of patients with skeletal muscle ischemia, the anatomical extent and the distribution of vascular injuries make the patients unsuitable for autologous vascular grafting. An alternative or complementary strategy to reconstructive surgery is therapeutic angiogenesis, which aims to amplify naturally occurring adaptive neovascularization of the injured muscle tissue. My research focuses on developing novel scaffolds incorporated with angiogenic mRNA as a therapeutic strategy for revascularization of ischemic skeletal muscle. Sustained delivery of angiogenic factors mRNA to the target cells will enhance the expression of encoding angiogenic proteins through the cells’ translational machinery, which eventually induces the formation of new blood vessels in the ischemic tissue. We are interested in studying the influence of physicochemical and morphological properties of the scaffold on mRNA release rate, transfection efficiency, structural stability and immunogenicity. This may eventually provide an innovative and promising therapeutic approach for vascular regeneration in broad range of ischemic diseases.
- PhD, Neuroscience, Karolinska Institute
- MSc, Biological Sciences and Bioengineering, Sabanci University
- BSc, Molecular Biology and Genetics, Bilkent University
- Reprogrammed stem cells are a promising research field for personalized regenerative medicine. In order to fully harvest the potential of these stem cells we need to understand how they are regulated by the microenvironmental factors which include secreted hormones or growth factors, composition of the extracellular matrix as well as its stiffness and topographical properties. In my project, I am investigating how the extracellular matrix components regulate the survival, function and behavior of endothelial cells as well as their differentiation from induced pluripotent stem cells (IPS). We are eventually aiming at improving the outcome of transplantation studies to treat ischemic tissues that are caused by peripheral arterial disease (PAD). I am also investigating the effects of hormones on endothelial function.
- Graduate Student, Department of Mechanical Engineering, Stanford University
- Frank is a second year graduate student in mechanical engineering. Cell therapies based on human endothelial cells (ECs) derived from induced pluripotent stem cells (iPSCs) look to be a promising option for treatment of ischemic cardiovascular diseases. To fully realize the therapeutic potential of such strategies, a deeper understanding of how these cells sense and respond to cues from the microenvironment is required. I am investigating how mechanical cues such as nanotopography and matrix stiffness can regulate cell behavior and fate and ultimately enhance regenerative capacity. Engineered cellular microsystems also provide an opportunity to study the role of mechanotransduction in normal and pathological cellular processes such as endothelial-to-mesenchymal transition. To this end, I am interested in using in-vitro disease models as powerful tools for providing insights into mechanobiology and translating this knowledge to improved clinical outcomes.
- Doctoral Student, Department of Chemical Engineering, Stanford University
- Ada is a doctoral student in chemical engineering that is co-mentored by Dr. Huang. Ada's research focuses on the rheology and multiscale biological dynamics of live cell monolayer sheets under shear. Her work takes advantage of a live cell monolayer rheometer (LCMR), developed in Gerald Fuller’s Research Group, which allows application of precise, uniform shear strains or shear stresses to live cell monolayers mounted on an imaging platform. By coupling the LCMR with real-time fluorescence imaging and carefully-selected molecular imaging probes, she is able to concurrently study the mechanics and biological response of living cell monolayers under shear force. In her current work, she is investigating the complex mechanics of the vascular endothelium, with the goal of revealing novel physical biomarkers for vascular function.
Cynthia Alcazar, BS
Lab Manager and Animal Technician
- BS, Animal Science, University of California, Davis
- Veterans who suffer from injuries to muscle tissue face difficulty repairing the damage and regaining normal function. This is caused by the destruction of cells in the affected region or the inadequate blood supply to the surrounding tissue. My work focuses on studying the revascularization and regeneration of cells in a hindlimb ischemia model. We are testing a stem-cell and hydrogel treatment with the aim to increase healing and rejuvenation.
- Undergraduate, Cañada College
- I am a Veteran who served in the US Marine Corps, and I am interested in pursuing biomedical research. Although there are several available treatment options for cardiovascular disease, it continues to be the deadliest and most expensive to treat in the US. Meanwhile advancements in medical technology have greatly increased the survival rate of casualties from the most recent military conflicts, creating a need for new and more efficient types of treatments. Bioengineers are working to create cardiac and muscle tissue implants composed of stem cell lined three-dimensional scaffolds. I will be working with a team to develop and refine a consistent process of electrospinning biodegradable polymers into precise aligned porous scaffolds required to deliver treatment to sites of tissue ischemia.
- Undergraduate Researcher, San Jose State University
- I am passionate about innovating new technologies. Current medical treatments for heart related illness can be improved, and I am excited to be working in this cutting-edge field of research. I will be fabricating 3-dimensional scaffolds using electrospinning that promote directional cell growth. As a Marine Corps Veteran, I hope to help this lab create new treatments to help veterans and other Americans maintain their health and live long fulfilling lives.
Caroline Hu, BS
- BS in Molecular & Cellular Biology, University of Illinois at Urbana-Champaign
- I am interested in investigating the development of vascular tissues, and understanding the mechanisms of vascular damage, healing, and regeneration. Using that knowledge and pluripotent stem cells, researchers are developing methods to optimize regeneration and revascularization in muscle tissues. I perform animal models of cardiovascular and muscular injuries to test the efficacy of engineered tissue-based therapies.
- Mechanical Engineering Undergraduate Student, University of California Davis
- I have had a long-standing interest in mechanical engineer and more recently biomedical engineering. My grandfather is a World War II veteran who has experience his own injuries and trauma. Being able to contribute to the wellbeing of our veterans is personally satisfying. I have been assisting in the study of the revascularization and regeneration of cells in a hindlimb ischemia model. Specifically, I am performing quantitative image analysis of histological tissue sections for vascularization. In addition, I have been doing mechanical design and 3D printing of devices for our tissue engineering platforms.
Guang Yang, PhD
- PhD, Bioengineering, University of Pittsburgh
- BS, University of Science and Technology of China
- Endothelial cells (ECs) derived from human induced pluripotent stem cells (iPSCs) represents a promising patient-specific cell source for the treatment of peripheral arterial disease (PAD), which is prevalent in the United States. Adequate survival and angiogenesis of cell implant are the key to fully exploit the potential of iPSC-ECs in vascular repair and regeneration. My research is aiming at understanding regulatory effect of aligned nanofibrillar collagen scaffold that mimics the native nanostructure of the blood vessel ECM on iPSC-EC fate and function. We hypothesize that the topographical cues presented by the scaffold will cause cell alignment and improve cell survival, proliferation and angiogenic activities under hypoxia. We envision this tissue engineering approach to be clinically translatable to improve the blood perfusion and vasculature of PAD patients.
- Undergraduate Intern, Department of Bioengineering, University of Illinois at Urbana-Champaign
- Future developments in tissue engineering and regenerative medicine will rely heavily upon biomimetic three-dimensional scaffolds. The generation of these scaffolds will require a comprehensive understanding of how cells respond to biomechanical interactions as well as microenvironmental cues. My work focuses on the development of non-thrombogenic vascular grafts and wet spinning of fibrous scaffolds for tissue engineering applications.
Luqia Hou, PhD
- PhD, Molecular & Integrative Physiology, University of Michigan
- MSc, Pharmacology, SUNY Upstate Medical University
- BSc, Biotechnology, Shandong University
- Over 8 million Americans are suffering from Peripheral Arteries Disease (PAD), which is due to atherosclerotic occlusion of the peripheral arteries of the limbs. Tissue engineering using induced pluripotent stem cells (iPSCs) derived endothelial cells serves as a promising approach for vascular repair. My project focuses on studying the role of microenvironment, the interaction between extracellular matrix (ECM) and integrin, in the iPSCs differentiation process by utilizing high throughput ECM microarray technique. I am also interested in optimizing the ECM composition to maintain the survival and function of iPSC derived endothelial cells in hypoxia, which mimic the in vivo condition of PAD patients.
Joseph Jung-Woong Kim, PhD
- PhD, Biomedical Engineering, Rutgers University
- MS, Biological Sciences, University of Medicine and Dentistry of New Jersey
- BA, Cell Biology and Neuroscience, Rutgers University
Zachary Strassberg, BSc
- BSc, McGill University, Montreal
Prajakta Joshi, MS (2014-2015)
- Graduate Student Research Assistant
- MS (Pharm) Biotechnology, NIPER (Ahmedabad), India
- BPharm Sc, Institute of Chemical Technology (Mumbai), India
Arshi Jha (2013)
Life Science Research Assistant
Brian Boursiquot, AB
- MD Candidate, Stanford University School of Medicine
- AB, Biomedical Engineering, Harvard University
Monica Gole, PhD
- PhD, Pharmaceutical Sciences (Pharmacology), University of Mississippi
- MS, Pharmaceutical Sciences (Pharmacology), University of Mississippi
- BS, Pharmaceutical Sciences, University of Mumbai