Research

Our ongoing bench research includes investigations of biologic effect variability in proton therapy as well as radiation effects on non-replicative cell types including neurons. We have extensive experience in both in vivo and in vitro biologic effect models of radiation-induced neuronal and cognitive dysfunction. Our ongoing research projects includes:

1. Revealing the role of the ventral tegmental area dopaminergic system, not only alterations at a neuronal level but also dysfunction in coupling with other brain regions, in radiation induced cognitive impairment. We, for the first time, seek to understand alterations in the midbrain dopaminergic system after brain radiation and mechanisms underlying these changes. With this new knowledge, we then seek to prevent or reverse these changes using drugs already approved for patient use for other neurodegenerative conditions to improve functional outcomes and quality of life for brain tumor survivors.
2. Determining the novel roles of microtubule-associated tau in radiation-induced neuronal damage. Tau is canonically associated with neuropathology but we are exploring the novel, neuroprotective functions of the protein in radiation. For the first time, we are showing phosphorylated tau plays a critical role in radiation-induced cell stress such as DNA damage repair, endoplasmic reticulum stress, and the translation machinery.
3. Investigating the impact of irradiation on neurons and uncover the protective mechanisms of memantine from radiation damage. Specifically, we intend to explore the effects of radiation on neuron structure and function by utilizing a customized high-resolution confocal microscope that enables real-time imaging coupled with irradiation. Furthermore, we plan to evaluate the protective effects of memantine on radiation-induced cognitive decline by conducting behavior tests. Through this research, we hope to gain a better understanding of the underlying mechanisms of radiation-induced neuronal damage and develop potential therapeutic strategies to mitigate its harmful effects.
4. Identifying long-term effects of ionization radiation on gene expression levels and DNA methylation status in hippocampus CA regions and prefrontal cortex of radiated brain in a mouse model. Performing computational analysis of single-nucleus RNA sequencing and Whole Genome Bisulfate Sequencing techniques to discover novel mechanisms that leads to molecular and structural changes in brain cells.
5. Studying the effects of particle radiation, protons and carbon ions, using novel cerebral brain organoids cultured with or without glioma stem-like cells. Here we seek to relate cellular response as a function of both dose and LET for light and heavy ion beams. We are also investigating a novel role for necroptosis in radiation response.