CRISPR-based editing reveals edge-specific effects in biological networks.
The CRISPR Journal, 2018.
Networks consist of functional elements (nodes) that form a variety of diverse connections (edges), with each node being a hub for multiple edges. Herein, in contrast to node-centric network perturbation and analysis approaches, we present a high-throughput CRISPR-based methodology for delineating the role of network edges.

Mapping the operational landscape of microRNAs in synthetic gene circuits.
NPJ Systems Biology and Applications, 2018.
We combined experiments and mathematical modeling to study the microRNA operational landscape. We engineered custom genetic circuits that contain microRNA-based regulation and introduced an analytical strategy, that includes clustering and superposition of discrete experiments, to produce a “bird’s-eye view” perspective.

Exploiting the CRISPR/Cas9 PAM constraint for single-nucleotide resolution interventions.
PLOS ONE, 2016.
We demonstrate that the PAM requirement can be exploited to specifically target single-nucleotide heterozygous mutations while exerting no aberrant effects on the wild-type alleles. Specifically, we target the heterozygous G13A activating mutation of KRAS in colorectal cancer cells and we show reversal of drug resistance to a MEK small-molecule inhibitor.

Discriminating direct and indirect connectivities in biological networks.
Proceedings of the National Academy of Sciences (PNAS), 2015.
We used a combination of computational and theoretical approaches coupled to synthetic biology experimentation in mammalian cells to study direct and indirect connectivities in biological networks.

CRISPR-based self-cleaving mechanism for controllable gene delivery in human cells.
Nucleic Acids Research, 2015.
We introduce a methodology to control the copies and residence time of a gene product delivered in host human cells but also selectively disrupt fragments of the delivery vehicle. We envision future applications in complex synthetic biology architectures, gene therapy and trace-free delivery.

Assembly and validation of versatile transcription activator-like effector libraries.
Scientific Reports, 2014.
Here we introduce, describe the assembly, and demonstrate the use of comprehensive and versatile transcription activator-like effector (TALE) libraries. Considering the highly modular nature of TALEs and the versatility and ease of constructing these libraries we envision broad implications for high-throughput genomic assays.

Biological 2-input decoder circuit in human cells.
ACS Synthetic Biology, 2014.
Decoders are combinational circuits that convert information from n inputs to a maximum of 2ⁿ outputs. We present the first implementation of a genetic decoder in human kidney cells.

Synthetic mammalian transgene negative autoregulation.
Nature/EMBO Molecular Systems Biology, 2013.
The effect of negative feedback on global and local sources of uncertainty is studied with synthetic circuits stably integrated in human cells. Negative feedback is shown to be the most efficient way to mitigate the effects of global fluctuations by introducing a single additional regulatory link.

Reverse engineering validation using a benchmark synthetic gene circuit in human cells.
ACS Synthetic Biology, 2013.
We stably integrate a synthetic gene network in human kidney cells and use it as a benchmark for validating reverse engineering methodologies.