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Marples Lab

Radiobiology Research Laboratory

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Investigator / Contact Person Brian Marples

Research

My main research focus is tumor and normal tissue radiobiology. These studies are designed to improve tumor eradication by maximizing tumor radiation response while minimizing toxicity of normal tissue. On-going studies include modulating the tumor microenvironment to improve treatment response of non-small-cell lung cancer with the central hypothesis that radiation fractionation can be used to control tumor microenvironment and reduce tumor growth and recurrence. Pre-clinical studies using head and neck xenografts are underway to improve survival of tobacco-associated squamous cancers, using radiation in combination with molecular-targeted chemotherapy agents against growth pathways specific to head and neck cancers. Other cell culture and xenograft studies are investigating the pattern of radiation delivery as a mechanism to exploit dose-dependent ATM-mediated DNA damage response pathways to improve the treatment of glioblastoma.

Complementary studies are examining radiation-induced normal tissue sequelae. We have recently shown that kidney irradiation induces loss of sphingomyelin-phosphodiesterase-acid-like-3b (SMPDL3b) expression in cultured podocytes, and alters podocyte sphingolipid homeostasis inducing loss of filopodia. After irradiation, we discovered that the actin-binding protein ezrin relocated from the podocyte plasma membrane to the cytosol, promoting cytoskeletal remodeling. Irradiation triggered a time-dependent loss of SMPDL3b and coincident elevation in ceramide levels, and reductions in sphingosine, sphingosine-1 phosphate and ceramide-1-phosphate. From these observations, we identified a novel lipid-based molecular pathway mediating radiation-induced podocyte injury that allowed the mitigation of long-term functional renal injury after kidney-targeted irradiation using a preclinical model.