BRAIN CANCER
We have assembled a team with an outstanding track record in exceptionally innovative research combining mathematical modeling of treatment response and mouse models of glioblastoma. In this proposal, we will (i) develop novel mathematical models that include the treatment effects of radiation, temozolomide (TMZ) and dexamethasone as well as additional genetic alterations; (ii) utilize novel mouse modeling systems that allow non-invasive monitoring of response; (iii) use novel cell culture systems that recapitulate the stem cell niche in these tumors; and (iv) use novel mouse modeling systems that allow acquisition of expression profiles in vivo from specific cell types, for instance cells with and without stem-like character.
LITERATURE CITED 1. Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP, Alexe G, Lawrence M, O'Kelly M, Tamayo P, Weir BA, Gabriel S, Winckler W, Gupta S, Jakkula L, Feiler HS, Hodgson JG, James CD, Sarkaria JN, Brennan C, Kahn A, Spellman PT, Wilson RK, Speed TP, Gray JW, Meyerson M, Getz G, Perou CM, Hayes DN, Cancer Genome Atlas Research. Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell. 2010;17(1):98-110. 2. Ozawa T, Riester M, Cheng Y, Huse JT, Squatrito M, Helmy K, Charles N, Michor F, Holland EC. Most human non-GCIMP glioblastoma subtypes evolve from a common proneural-like precursor glioma. Cancer Cell. 2014;26: 288-300.
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