(6lu) Bionanotechnology: DNA Nanotechnology-based Molecular Devices, Bio-sensors, and Hybrid Materials forBiological and Nanophotonic Applications

Research Interests: Bionanotechnology has emerged as a new paradigm to study biological processes, many of which occur at the nanoscale, and to design next-generation sensors and diagnostics. My laboratory will advance the field of bionanotechnology by developing DNA-based molecular bio-sensors, devices, and hybrid materials that will be used to address biological questions regarding cooperativity amongst cell receptor-binding ligands (Project 1), to solve problems in biological detection, e.g., the detection of low abundant circulating tumor DNAs (ctDNAs) (Project 2), and to further our understanding in nanophotonics by designing programmable nanophotonic materials for application in biology and energy (Project 3). Our ultimate goal is to understand biological processes in a more profound sense, by utilizing multidisciplinary approaches at the intersection of biology, materials, and biophysics and to apply such knowledge to design next-generation therapies and diagnostics.

Project 1: It is known that ligand cooperativity regulates cellular behavior. For example, the cooperativity between RGD (Arginylglycylaspartic acid) and BMP (Bone morphogenetic protein) enhances transcriptional activity that promotes osteogenic differentiation in hMSCs (Human Mesenchymal Stem cells), and RGD and VEGF (Vascular endothelial growth factor) regulates vascularization of endothelial cells. These interactions occur at nanoscale distances. Due to the lack of technology to spatially control the distance, density, and ratio between and amongst ligands, such cooperative phenomena have not been explored and investigated. Using DNA origami, I propose to engineer molecular rulers to investigate these cooperativities and apply the developed tools to study other molecular interactions. Project 2: Quantitative detection of circulating tumor DNAs (ctDNAs) in cancer patients is essential for early cancer diagnosis and precision medicine, but they are very difficult to quantify because of the low abundance in the blood. Based on the highly specific binding properties of DNA, I envision to develop DNA sensors as a novel and practical approach to solve this problem. Project 3: We are in great need of novel technologies for energy and nanophotonic applications. To address this, my group will develop hybrid-nanomaterials composed of natural photosynthetic systems and/or photonic materials/nanoparticles using self-assembled and highly programmable 3D DNA nanostructures to spatially arrange proteins, fluorophores, nanoparticles, and other molecules and moieties in the nanoscale. Beyond the projects, as mentioned earlier, my group will be interested in exploring other innovative ideas in a broad range of areas, including drug delivery. To advance the research in my group, I will engage in active collaborations with other faculty members, especially with computational groups and biology groups within the department and the university.

Research Accomplishments: During my doctoral research in Prof. Hao Yan’s and Prof. Yan Liu’s laboratory at Arizona State University, I invented DNA nanostructure-based multi-chromophoric artificial light-harvesting antenna systems and investigated the photonic properties using various spectroscopic methods, including fluorescence spectroscopy, time-correlated single-photon counting, Streak camera, ultrafast pump-probe spectroscopy and other optical spectroscopic methods (JACS 2011, JACS 2014, JACS 2014). These studies furthered our fundamental understanding of multi-chromophoric systems and paved the path for designing and developing more complex and sophisticated artificial light-harvesting antenna systems for energy and bio-switch applications. After finishing my Ph.D., I joined Prof. Yonggang Ke’s laboratory in the Department of BME at Georgia Institute of Technology and Emory University, as a postdoctoral fellow, to design and test complex DNA origami structures for nanophotonic (JACS 2016, ACS Nano 2017) and mechanobiological applications (Nano Letters 2018). To gain more biological insights in mechanobiology, I pursued a second postdoc in Prof. Christopher Chen’s laboratory at Boston University and Harvard Medical School. After joining, I developed a-actinin tension sensors to investigate the mechanobiology of sarcomerogenesis in iPSC-derived (induced pluripotent stem cell) cardiomyocytes, and I employed DNA origami to spatially control ligand molecules to study cell adhesion and signaling. While working in Prof. Chen’s laboratory, I also learned various micro-patterning and microfluidic device design techniques. In conclusion, during my research training, I have gained vast knowledge and acquired a unique skill set in DNA nanotechnology, nanomaterials, biophysics, analytical science, surface/conjugation chemistry, and cell biology, which will enable me to develop an exciting and transformative research program in bionanotechnology.

Funding: I have prior experience in writing NIH-R21 proposal with my previous advisor, which was granted. This experience will help me to write two NIH-R21 proposals for Project-1 and -2, and a NSF proposal for Project 3, immediately after my joining as a faculty. Also, the initial results from these three projects will help me to write proposals for RO1 grants. I will also seek grants from DoD, ARO, and DoE and funding opportunities from pharmaceutical companies and private foundations.

Teaching Interests: Aside from my research career, I also have enjoyed teaching/mentoring. At Arizona State University, I was an Organic Chemistry Teaching Assistant for two semesters. I also have mentored several high school, undergraduate, and graduate students during Ph.D. and Postdoctoral studies. I believe that as a mentor, my role is to motivate the students and stimulate their thinking and problem-solving capabilities. I am fully committed to facilitating these goals by setting up an engaging teaching environment. As a faculty, I would like to teach courses at both undergraduate and graduate levels, covering fundamentals of fluorescence, biophysics, analytical chemistry, and physical chemistry. I would also like to introduce graduate-level courses in bionanotechnology and its applications in various research areas, and instrumentations (spectroscopy, optical microscopy, electron microscopy).