Welcome to the C. Ryan Miller Laboratory
Diffuse gliomas are a diverse group of primary brain tumors. The most malignant of these, glioblastoma (GBM), is currently diagnosed by microscopic morphology and treated empirically with concurrent fractionated external beam radiation (XRT) and the DNA alkylating agent temozolomide (TMZ) to yield a median overall survival of 12-14 months. Neither diagnosis nor therapy is based upon the underlying molecular alterations responsible for gliomagenesis, the roles of which are becoming increasingly defined through the use of genetically-engineered mouse models (GEMM). The main goal of our work is to establish a direct link between preclinical drug development in GBM GEMM and the rational design of human clinical trials involving patients with molecular subtypes of GBM through use of comparative molecular analyses to
1) molecularly stratify human GBM with distinct responses to chemoradiation;
2) define the roles of cell-of-origin and genetics in GEM GBM subtype-specification; and
3) define molecular signatures of TMZ-XRT-resistant GEM and recurrent human GBM.