Our lab uses the tools of chemistry, molecular biology, and computational design to engineer proteins and nucleic acids as self-assembling nanoscale devices. Such devices include molecular barcodes for labeling, timers for kinetic analysis, rulers for measuring distances, printers for molecular manufacturing, and computers for multi-signal processing. Through the application of these tools, our goal is to define the cell-types, cell-states, and cell-cell interactions that underlie the dynamics of disease progression and drug resistance.
Our lab employs a variety of skillsets and techniques, and combines experimentation with computation. Students in the lab gain a broad spectrum of skills including molecular techniques, biochemistry, imaging, coding, device fabrication, and much more.
We are proud to be a multidisciplinary group, and welcome applicants from diverse fields including but not limited to biology, chemistry, physics, engineering, and computer science. All we require is that you’re driven, innovative, self-motivated, and curious with a passion. We also believe that an academic career should not be the only reason to pursue graduate research, and we actively work on projects that can lead to innovative careers including start-up and spin-off ventures. If you are interested in working with us, you can find the application process here!
Cell-type diversity and cell-cell interactions underlie the formation of multicellular tissues and diseases such as cancer. These interactions invovlve both soluble signaling and physical contacts between cells, and together form a ‘signaling circuit’ that determines tissue-level behaviors. Many emerging cancer drugs, such as immune checkpoint inhibitors and CAR-T cells, are designed to disrupt specific nodes of the signaling circuit. Yet these drugs currently only work in a fraction of patients, suggesting that they are not targeting the most critical signaling nodes in the circuit, and/or that there exists redundant nodes which remain untargeted. Deciphering the nature of this circuit is the first and foremost challenge towards precision and personalized medicine.
The field of DNA nanotechnology has developed a suite of programmable tools for bottom-up molecular barcoding, sensing, and nanofabrication. The current focus of our lab is to use these tools for precise, multiplexed, and spatially resolved cellular analysis and manipulation. Ultimately, this will allow us to build predictive models of drug resistance and rationally designed drugs. Specific projects are detailed below:
Below you will find a list of our current and past projects. These projects revolve around the themes listed above. And yes, Leo enjoys coming up with cryptic project code names, a habit he picked up from his postdoc days :-)*
We design nucleic acid-based transcription factors to make in vitro gene regulatory networks scalable and programmable
We are using DNA-encoded molecular circuitry to rapidly sort cells. This could be useful for isolating rare cell populations or stem …
We are creating synthetic biology methods to barcode large libraries of proteins with DNA barcodes in a parallel manner so as to enable …
We are developing DNA-based encoding schemes to enable highly-multiplexed in situ protein imaging in cells and clinical tissue …
We use a spatially programmable capsule made of DNA to organize an enzymatic cascade for coordinated RNA manufacturing
We are using DNA-powered synthetic gene networks to create an in vitro operating system for molecular computing
We are creating moleculars computers that can diagnose diseases without the need for instrumentation