Investigator, Assoc Prof (M) Radiation Oncology, Mass General Research Institute

Associate Professor of Radiation Oncology Harvard Medical School

biological modeling; cell scale effects; dose-rate effects; flash radiation therapy; gold nanoparticles; monte carlo method; protons; radiation dosage; radiotherapy dosage; radiotherapy planning computer-assisted; scattering radiation; track structure monte carlo

In radiation oncology, tumors are irradiated with different types of radiation, most commonly with photons, but increasingly also with protons and other ions. The goal is to eliminate tumor cells while sparing the surrounding healthy tissue. Phenomenological concepts, such as the tumor control probability and relative biological effectiveness (RBE) models, play an important role in investigating connections of radiation modalities to clinically observed effects, particularly concerning toxicities. However, in order to fully understand the underlying mechanisms of radiation damage and repair, one has to investigate the mesoscale processes. Such complex biological concepts can only be fully explained in a mechanistic step by step approach. 

The focus of my research lab is to understand cellular processes in response to radiation insult, aiming at optimizing strategies for cancer radiation therapy. Computational methods are exceptionally useful to investigate the interactions of initial damage induction via ionization events (physics) followed by resulting radiolysis processes (chemistry) and the eventual mechanisms of cell repair (biology). I employ an experimentally-guided, multi-scale, cross-disciplinary approach to advance our understanding of the fundamental biological response of cells to radiation and to test and design new treatments.

My work focuses on three areas:

1)    Mechanistic Modeling: Developing accurate representations of cells and their sub-structures for simulations of damage induction during radiation exposure, modeling the DNA repair kinetics, exploring effects of non-nuclear components, and elucidating the underlying cell response mechanisms.

2)    Gold nanoparticles (GNP): Investigating the radiosensitization effects of GNPs, determining the biological targets and underlying mechanisms to optimize therapeutic approaches and increase tumor specificity and efficacy.

3)    Flash therapy: Identifying the underlying mechanism of how extremely high dose rate irradiations (>100 Gy/s), also termed Flash therapy, spare normal tissue while not affecting tumor response.