Recent advances in stem cell and developmental biology have enabled us to create in vitro miniature analogs of human organs known as organoids, which replicate the anatomical structures and functions of living human organs. Probing organoids to understand how cells interact with each other and their environment to build tissues and organs offers exciting opportunities for modeling human health and disease in a more realistic manner that may potentially revolutionize the future of biomedical research, drug discovery, and regenerative medicine. Our primary research interest lies in pioneering cutting-edge stem cell bioengineering strategies to develop i) microengineered organoid model systems of human tissues and organs, ii) machine learning-guided organoid patterning and morphogenesis on a chip, iii) tissue stem cell-based biomedical devices for sensory augmentation , and iv) self-assembled transplantable tissues and organs. We plan to utilize these systems to uncover the mechanisms underlying various human diseases and developmental processes and develop next-generation tissue engineering methods and sensing/screening platforms essential for successful applications in drug discovery, diagnostics, and regenerative medicine.

Human Organoids-on-a-Chip

By harnessing the self-organizing properties of pluripotent or adult stem cells, we can create 3D tissue constructs called organoids, which are miniature analogs of living human organs. This bioengineering approach offers new avenues in biomedicine for studying organ development, homeostasis, and disease. Yet, challenges remain in controlling and analyzing organoids. Our work combines organ-on-a-chip technology with organoids to create a controlled microenvironment for generating organoids. We are particularly interested in lung, intestine, and eye diseases, investigating how biochemical and biomechanical signals affect the structure and function of tissues in diseases. We aim to test drug agents and assess toxicity from nutritional and environmental factors. Our interest extends to retinal organoids for age-related macular degeneration and diabetic retinopathy research, studying disease progression and potential treatments. The ultimate goal of our work is to develop multi-organoid devices that simulate tissue-tissue and organ-organ interactions for comprehensive human disease modeling.

Organoid-Machine Interface for Tissue Patterning and Morphogenesis on Chip

Morphogenesis drives the transition from single stem cells to complex multicellular organisms. For example, lung branching and intestinal budding are pivotal for their respective functions. Our project employs organoids to replicate morphogenesis, coupled with a machine learning approach. Using this morphogenesis-on-a-chip, we are interested in studying the mechanisms that drive complex tissue formation. Our primary focus involves using computer-interfaced organoid platforms to analyze the real-time branching of lung and intestinal organoids at various developmental stages. This will help us identify signaling molecules responsible for cellular and structural complexity, which can be targeted to enhance tissue regeneration after injury. Additionally, we aim to bridge gaps in the development, regeneration, and disease progression of the crypt-villus axis in the intestine. This innovative approach facilitates the analysis of organoid symmetry breaking and spatial coupling, advancing tissue engineering for regenerative medicine.

Sensory Augmentation Biomedical Devices

Sense organs are specialized organs that help us interact with the environment by providing information for interpretation through a network of nerves. Our research focuses on developing biomedical devices that exploit these unique properties by incorporating various sensory receptor cells to achieve autonomous functions for biomedical and environmental applications. For example, we are interested in reproducing the chemically triggered sensory olfactory mechanism responsible for the sense of smelling in the nose to develop platforms for the detection of hormones and hazards. Inspired by the ability of dogs to detect various human diseases through smell, we plan to use this device to identify the distinctive characteristics of the disease-bearing human samples. Another bioinspired system that we plan to develop is a tongue-on-a-chip that reconstitutes taste receptors in the tongue. We are interested in creating systems that incorporate tongue organoids and mimic the transduction of bitter, sweet, and umami taste receptors to reproduce the sensing of food particles. We will utilize these biomimetic systems to study the mechanisms of taste perception and establish human cell-based models that can be used to distinguish the complex flavor profiles of food particles for accurate taste testing of newly developed food additives and drug substances.  

Engineered Transplantable Tissues and Organs

Stem or progenitor cells have an incredible capability to repair and replace damaged parts of the body in response to injuries or diseases. These regenerative processes in biological systems are essential for the normal and pathological function of cells and organs and are remarkable examples of self-repair mechanisms with great potential for the development of self-assembled implantable tissues and organs for regenerative therapies. Our lab harnesses these mechanisms to create stem cell-based transplantable tissues and organs for the efficient regeneration of native organs. Specifically, we are interested in engineering transplantable tissue parts using patient-derived induced pluripotent stem cells, which will offer the opportunity to restore damaged tissue with healthy ones. We also plan to develop three-dimensional organ chip systems to provide vascular perfusion and support during tissue differentiation and maturation processes. These engineering strategies will be applied to the development and improvement of vascularized tissues for organ replacement therapy.