“Molecular Imaging and Cellular Reprogramming in Immuno-engineering”
Peter Yingxiao Wang, Ph.D.
Professor of Bioengineering
Department of Bioengineering
Institute of Engineering in Medicine
University of California, San Diego
Genetically-encoded biosensors based on fluorescence proteins (FPs) and fluorescence resonance energy transfer (FRET) have enabled the specific targeting and visualization of signaling events in live cells with high spatiotemporal resolutions. FRET biosensors have been successfully developed to monitor the activity of a variety of signaling molecules, including tyrosine/serine/threonine kinases. We have a developed a general high-throughput screening (HTS) method based on directed evolution to develop sensitive and specific FRET biosensors which allowed the visualization of signaling activation patterns in live immune cells. It has also been increasingly clear that controlling protein functions can control cellular behaviors for therapeutics. We have engineered a novel class of machinery molecules which can provide a surveillance of the intracellular space, visualizing the spatiotemporal patterns of molecular events and automatically triggering corresponding molecular actions to guide cellular functions. We have adopted a modular assembly approach to develop these machinery molecules, and applied them to reprogram the “don’t eat me” CD47 receptor SIRPa on macrophages such that the engagement of SIRPa and its activation of naturally negative signals will be rewired to turn on positive actions to facilitate phagocytosis of red blood cells and target tumor cells. Because of the modular design of our engineered molecule, our approach can be extended to perform a broad range of cell-based imaging and immunotherapies, and hence highlight the translational power in bridging the fundamental molecular engineering to clinical medicine. We have further integrated with lights and ultrasound to control the molecular activations of genes and enzymes, which allowed us to control the cellular functions of immunocells for therapeutics with high precision in space and time.
Peter Wang, Ph.D., obtained his bachelor’s and master’s degrees in Mechanics and Fluid Mechanics from Peking University, Beijing, P.R. China, in 1992 and 1996, respectively. He received his Ph.D. degree in Bioengineering from UC, San Diego in 2002 and continued his postdoctoral work at UC San Diego working under Bioengineering Professor Shu Chien and Professor Roger Y. Tsien in the Department of Pharmacology. He is current a professor at the department of Bioengineering at UCSD and a fellow of American Institute of Medical and Biological Engineering (AIMBE). Before joining the UC San Diego faculty in 2012, he was an associate professor at the University of Illinois, Urbana-Champaign (UIUC), Department of Bioengineering and a full-time faculty member in the Beckman Institute for Advanced Science and Technology at the University of Illinois. Dr. Wang is the recipient of the Wallace H. Coulter Early Career Award (both Phase I and Phase II), the National Science Foundation CAREER Award, and National Institutes of Health Independent Scientist Award. His research is supported by the National Institutes of Health, National Science Foundation, and private foundations.