MVL Seminar: Robert Hinshaw (9a, 33-218, 11/17)

January 10, 2018

Robert Hinshaw

MEMP Bioastronautics
Harvard-MIT Health Science & Technology (HST) Program


The central nervous system, once thought to be relatively radioresistant, has been shown to be susceptible to low doses of high charge and energy (HZE) particle radiation, and I hypothesize that maladaptive glial activation driven primarily by microglia mediates this radiation-induced damage. The specific goal of this work is to determine the spatiotemporal response of microglia to tracks of particle radiation so that their role in neuronal damage may be better understood. I aim first to modify a CX3CR1-GFP mouse organotypic brain slice culture model to be compatible with Columbia University’s Radiological Research Accelerator Facility (RARAF) microbeam system, which will allow for precise deposition of particle radiation in neural tissue. I will test this model first with exposure to broadbeam HZE radiation at the Brookhaven National Laboratory to demonstrate that the resulting neural damage is dependent on microglia, which will be selectively eliminated by chemical treatment. My second aim is to use the RARAF microbeam system to determine the spatiotemporal response of microglia in unirradiated tissue to nearby particle traversals. This will be the first experimental system able to observe the interaction between irradiated and unirradiated mammalian neural tissue. Based on the published literature, I expect to see microglia in unirradiated tissue express an activated phenotype and migrate towards the neurons damaged by particle traversals. My final aim is to use two independent 3D human neural culture systems developed by our collaborators as models of Alzheimer’s disease to test the hypothesis that genotypes linked to the disease -specifically the Apo E allele and APP mutations- confer a greater susceptibility to radiation-induced neurodegeneration. These models notably do not contain microglia, but characterizing their radiation response in the absence of microglia will lay the groundwork for future investigations in emerging human microglia/neuron coculture models and the genetic link between chronic neuroinflammation and neurodegeneration.