Our research focuses on a key bottleneck in precision medicine: the disconnect between the molecular design of a drug and its actual behavior within a patient. Although next-generation bispecific antibodies, genetic therapies, and targeted small molecules have proven efficacy and hold transformative potential, their clinical utility is often capped by dose-limiting toxicities and insufficient uniform accumulation within diseased tissues. To address this issue, we engineer site-specific systems, ranging from radiation-activated conjugates to ultrasound-responsive agents, that respond to external triggers to release their payloads. Recent work includes radiation-activated antibody-drug conjugates and scintillating nanoparticle depots that convert ionizing radiation into local drug release. These promise to maximize local efficacy while minimizing systemic toxicity.

Radiation therapy is a cornerstone of cancer treatment, and the precision with which it can be delivered to tissues is continually improving with the development of conformal and adaptive treatments, molecularly-targeted radiopharmaceuticals, and new imaging capabilities. Our research investigates the impact of radiation on the tumor microenvironment, and in turn, how the microenvironment influences radiation response. A key objective is to use this understanding to identify and engineer new strategies for safely maximizing the effectiveness of radiation and radioconjugate treatments while using lower doses with improved safety.

Thousands of biomaterials and nanoparticles have been developed for drug and nucleic acid delivery, but molecular and cellular-level mechanisms of their action in tissue are often poorly understood. Our group expands on novel in vivo imaging techniques to analyze the combined distribution and action of biomaterials and nanoformulations at a multi-scale level. This project pursues a systematic, molecular-level understanding of drug action, with the goal of informing improved therapeutic and biomaterial designs.

Through new technologies, including single-cell RNA sequencing (scRNAseq) and multiplexed tissue imaging (MTI), tissues can now be visualized with incredible molecular and cellular detail. However, such rich maps of tissue structure are typically static snapshots from a fixed sample, and lack important information about how the tissue actually functions — how cells, fluids, and biomolecules dynamically interact to govern multicellular behaviors. This project aims to overcome this limitation by building an integrated computational and experimental platform for quantitatively linking functional dynamics within tissue to a map of its molecular and cellular composition.