Our research integrates advanced protein design, translational synthetic biology, and deep-tissue optical technologies to develop next-generation tools for biomedical discovery and therapy. Our work centers on molecular engineering for next-generation health technologies, aiming to create programmable molecular systems that sense, report, compute, and control cellular states with high precision.
Near-Infrared Optogenetics and All-Optical Technologies. We develop near-infrared optogenetic systems, molecular biosensors, and fluorescent proteins that enable spatiotemporally precise control of cellular processes deep within living tissues. By combining genetically encoded optical biosensors and non-opsin optogenetic actuators with spectrally separated fluorescent and photoacoustic reporters, we design fully optical methods for both perturbing and monitoring biological activity in real time. These tools allow the manipulation of molecular pathways in intact tissues with minimal invasiveness and high spatial resolution. We apply these all-optical strategies to systems ranging from molecular signaling networks to translational applications. Local illumination can activate engineered immune cells or therapeutic viral vectors selectively, confining functional responses to defined tissues while maintaining systemic safety. This direction establishes a foundation for quantitative, light-guided modulation of gene expression, cell signaling, and intercellular communication.
Synthetic Biology Targeting Intracellular Disease Drivers. We design synthetic molecular systems that convert intracellular disease states into programmable biological responses. Target-stabilizable binders, such as nanobody-derived modules that become stable and active only in the presence of their intracellular targets, serve as versatile building blocks for intracellular sensing and control. These binders act as molecular switches, enabling highly specific activation of immune effectors, transcriptional programs, or genome-editing modules exclusively in diseased cells. This strategy opens new opportunities for precision medicine by targeting intracellular proteins that have remained inaccessible to conventional antibody-based therapeutics. In cancer models, for instance, oncogene expression can conditionally trigger immune engagement or checkpoint modulation, enabling cell-selective interventions without affecting normal cells. More broadly, this technology supports a flexible framework for intracellular diagnostics and treatment design across cancer, inflammatory, metabolic, and infectious diseases.
Intracellular Logic Circuits for Cell Programming. We explore how complex cellular behaviors can be represented and engineered using molecular logic circuits operating entirely within the cell. These circuits, built from target-stabilizable binders and related components, integrate multiple dynamic inputs, such as transient signaling events or activation timing, into defined molecular outputs. By coupling sensing, reporting, computation, and actuation within a single molecular architecture, cells can be programmed to execute context-dependent responses autonomously. This approach is applied to immune and neural systems where precise information processing is essential. In engineered T cells, logic operations such as coincidence detection and ratio sensing allow finely tuned activation, minimizing aberrant signaling and functional exhaustion. In astrocytes, logic-gated designs interpret inflammatory and neuromodulatory cues to selectively mitigate pathological responses. Through this research, we aim to establish intracellular computation as a new layer of biological control and therapeutic modulation.
Together, these directions form an integrated research program that advances protein-based tools for precise control and quantitative understanding of complex biological systems. The resulting approaches create broadly applicable molecular platforms that bridge fundamental discovery and technological innovation across diverse areas of biology and medicine.