Our lab focuses on the integration of biotechnologies in cellular and molecular engineering for the development of genetically-encoded biosensors and the application of them to visualize molecular events in live cells and animals. We also develop molecular sensors and transducers for the engineering of immune cells to control genetic and epigenetic activities targeting cancer immunotherapy. For example, we engineer CAR T cells and macrophages so that they can be remotely and non-invasively controlled by ultrasound waves to recognize and eradicate tumors. Several examples of our research interest are listed as following:

"A Drunk Cell Dancing" - Airport Art Exhibit

This image shows the activation process of a kinase in a live cell. Initially the cell shows a blue color indicating low activity (2 o'clock position). After stimulation, the cell turns green and then turns red counterclockwise, indicating kinase activation.

1) Developing genetically-encoded reporters based on fluorescent resonance energy transfer (FRET) to visualize and quantify signaling transduction in live cells with high tempo-spatial resolution;

The 3D structures of the Src reporter before Src activation.

The 3D structures of the Src reporter after Src activation.

The movie shows effects of EGF stimulation and washout on FRET responses of the monomeric Src reporter in HeLa cells.

The EGF-induced FRET response in HeLa cells expressing the Src reporter.

PP1 reversed the EGF-induced FRET responses of the membrane-targeted Src reporter in HeLa cells.

2) Combining red fluorescence protein (RFP) together with CFP/YFP-based FRET reporters to simultaneously visualize multiple signaling events and elucidate the molecular hierarchy involved in cellular signaling transduction;

3) Integrating Nano-fabrication, Laser-Tweezer, and Multi-photon Microscopy, together with fluorescence probes, to manipulate and visualize the regulatory signaling cascades in live cell motility and migration.

The movie shows a highlighted cell with a clear FRET wave propagation away from the stimulation site upon force application.

The laser-tweezer-traction induced directional and long-range propagation of FRET responses of the membrane-targeted Src reporter in HUVECs.

The laser-tweezer-traction on a polylysine-coated bead did not induce FRET responses in HUVECs.

4) Detecting early cancer development in biopsy samples with FRET-based reporters.

5) Image-driven system biology: Intra-cellular transport and diffusion by finite-element-analysis.

6) High throughput image analysis software for automatic quantification of molecular activities and statistical inference.

We are very grateful to the following agencies for their generous support:

Beckman Laser Institute, Inc.

Grainger Foundation, Inc.