Our lab combines theoretical and experimental approaches to better understand the fundamental mechanisms of how cells and tissues respond to radiation. We integrate advanced modeling with cutting-edge biological and chemical experiments to bridge physics, chemistry, and biology.
Macroscopic Monte Carlo simulations
We are part of the core team that develops and maintains the TOPAS Monte Carlo code. TOPAS (since the OpenTOPAS release) is a fully open software offering accurate simulations at the CT scale for multiple radiation therapy and imaging approaches.Our lab focusses on understanding the underlying mechanisms of cell and tissue response to radiation. To gain a better understanding of the mechanisms, we combine Monte Carlo simulations of radiation induced damages on sub-cellular targets followed by mechanistic modeling of DNA repair kinetics with radiobiology experiments.
Cell-Scale Monte Carlo Simulations
We use Monte Carlo simulations to model radiation-induced damage at the sub-cellular level and pair these with mechanistic models of DNA repair kinetics and radiobiological experiments. Our framework (TOPAS-nBio) builds the basis of many of our studies, including studiying:
- The impact of DNA organization on radiation sensitivity
- Radiation-triggered prodrug release
- Radiation enhancement using nanoparticles
- Mechanisms of healthy tissue sparing at ultra-high dose rates (UHDR)
The FLASH Effect
UHDR irradiation has been observed to spare healthy tissue while maintaining tumor control. This phenomenon is known as the FLASH effect, which could be a game-changer in radiation therapy. However, many questions remain, including identifying the underlying mechanism. To explore these, we integrate:
- Mechanistic modeling
- Radiation chemistry experiments
- In vivo and in vitro studies
Multi-Scale Cellular Automaton Models
Some radiation effects arise from interactions across multiple spatial scales. Our cellular automaton models capture how microenvironmental factors, such as oxygen gradients and vascular supply, influence radiation response beyond the single-cell level.
Prodrug Release
Delivery and radiation-mirigated activation of prodrugs offers a dual targeting, combining drug delivery with radiation targeting. The Miller Lab has designed a class of radiation-activated prodrugs that uncage selectively in response to radiation-generated reactive species including free radicals generated during radiolysis. Collaboratively, we apply TOPAS-nBio simulations to understand the underlying mechanisms and chemical reactions responsible for drug activation.
Nanoparticles
Our lab has a long history in nanoparticle research. We initially focused on gold nanoparticles (GNPs) and their physics-driven radiation enhancement effects. However, biologically observed radiation sensitization greatly outperforms dose enhancement from Auger electrons. Our studies now focus on the radiation chemical effect due to the presence of (metallic) nanoparticles and expand to include non-nuclear effects and non-gold nanoparticles.
Radiopharmaceuticals
Radiopharmaceutical therapy (RPT) offer a systemic delivery of radiation, targeting multiple leasions at once, potentially destroying all metastases. Additionally, immune activation may further drive metastatic tumor control. With the correct targeting moeities, RPT thus offers the potential to target all tumor cells in a patient. RPT can choose from radionuclides emitting photons, electrons and alpha particles and various chelating agents to target cells. However, toxicities remain a limiting factor. To optimize outcomes, we need to better understand cell and tissue level responses, and move to a more patient-specific dosimetry. We investigate the cell-scale effects, while the latter part is the focus of the blab.