Loma Linda University

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Xiao Mao, MD
Assoc Res Prof, Basic Sciences
School of Medicine
Assoc Res Prof, Radiation Medicine
School of Medicine
Member, Research, SM, Faculty of Graduate Studies

My research has started with investigating normal tissue radiation dose response to proton beam irradiation and focus on radiation-induced normal vascular in central nervous system.  Both the dose response of the vasculature of a cancer being treated and the response of the vasculature in surrounding normal tissues are important parameters. Quantitative data on cell population changes were lacking. While vessel changes have been described histologically previously they have never been quantified. This is believed to have resulted because of the lack of a suitable model and the absence of necessary techniques. With mycollaborators, I have developed a novel model for vasculature studies based on the brain and retina. The initial study required identifying an appropriate animal model. In collaboration with Dr. G. Robison at the National Eye Institute the rat retinal digest model was identified. This model allowed separation of the retinal microvessels from the retina. Collaboration with Dr. Lucie Kubinova in the Academy of Sciences of the CzeckRepublic has been established to utilize confocal laser scanning microscopy to perform the stereology techniques to quantify vascular changes. Stereological methods allow rigorous quantitative evaluation of the structure of three-dimensional (3-D) objects. Based on these animal model and quantification techniques, as a co-investigator, a NASA grant was rewarded to determine the dose response of Iron-56 on brain and retina microvasculature. Also as a co-investigator for a NASA NSCOR grant, focus on quantifying the cellular composition of mouse brain vascular endothelium using confocal stereological analysis of preserved tissue. A manuscript published on Radiation Research was selected as cover page and selected for Podcast. 

In past several years, my research has focus on identifying factors and cellular mechanisms which trigger radiation and oxidative stress-induced microvascular and tissue remodeling in retina and brain.  Our gene expression analysis of rat retina showed that radiation-induced changes in gene expression relating to oxidative stress and apoptosis in retinal cells. That study led us to investigate molecular mechanisms of proton radiation-induced oxidative damage to retinal cells by evaluating expression of genes and proteins associated with mitochondria and the potentially protective role of MnTE-2-PyP. The data demonstrated that proton radiation induced mitochondrial apoptosis and altered mitochondrial function in retina. Currently, there are no safe and highly effective radioprotective drugs available for reducing ocular damage from medical or occupation-related radiation exposure. The metalloporphyrin antioxidant mimetic MnTE-2-PyP has been shown to have excellent pharmaco­dynamic properties that allow it to reach and penetrate target tissues at efficacious concentrations that are not associated with significant toxic side effects. With support from our collaborator, Dr. James Crapo, this metalloporphyrin compound showed  that it has potential to protect cells against radiation-induced oxidative damage by controlling the generation of mitochondrial ROS. This agent can be considered for translational studies to use in radiation therapy as a therapeutic radioprotector.