Program Project Grant

This year marked the ninth cycle of Program Project Grant funding for the UCSF Brain Tumor Center from the NIH. The Center’s first Program Project Grant was awarded in 1979 to study the biology and therapy of malignant brain tumors. Since then, the program has evolved to focus on developing and applying novel noninvasive neuroimaging techniques to clinical problems in neuro-oncology.

In the last decade, delineation of histopathological and molecular subgroups of glioma has revolutionized the field of neuro-oncology by improving diagnosis and prognosis. Interrogating metabolic and physiologic signatures of these subgroups will be one of the next critical advances in the field of neuroimaging. For the next four years, the program will focus on four projects aimed at improving the management of patients with different subgroups of glioma.

Project 1: Improved Strategies for Noninvasive Imaging of Patients with Glioma

Project Leader: Janine Lupo, PhD
Co-Investigators: Annette Molinaro, PhD; Javier Villanueva-Meyer, MD; Valentina Pedoia, PhD; and Mitchel Berger, MD

This project will link metabolic and physiological imaging data with histological characteristics from 2000 image-guided tissue samples obtained from 750 patients in our previous funding cycle and will validate them prospectively in a new cohort of patients. This multi-parametric approach will produce metrics tailored to each molecular subgroup of glioma.

Project 2: Investigating Mechanisms that Regulate Tumor Cell Immortality in TERT-promoter-mutant Glioma

Project Leader: Joseph Costello, PhD
Co-Investigators: Jennifer Doudna, PhD and Annette Molinaro, PhD

Delineating the regulators of tumor immortalization that are associated with TERT promoter mutations is highly significant for providing a better understanding of the formation and evolution of glioma. Project 2 aims to identify subgroup-specific and shared factors that influence how the TERT promoter mutation impacts tumor progression for glioblastoma and oligodendroglioma, which have such divergent clinical outcomes.

Project 3: Defining Metabolic Signatures for Monitoring TERT Expression in Glioma

Project Leader: Sabrina Ronen, PhD
Co-Investigators: Russell Pieper, PhD and Annette Molinaro, PhD

This project will use 1H and hyperpolarized 13C MR spectroscopy in cell and pre-clinical models to identify signatures of TERT expression that could be used for monitoring tumor progression and assessing response to therapy. This would be highly significant for the initial screening of promising therapeutic agents aimed at TERT promoter-mutant cells.

Project 4: Translating 1H and Hyperpolarized 13C Metabolic Imaging Techniques to Patients

Project Leader: Daniel Vigneron, PhD
Co-Investigators: Yan Li, MD, PhD; Susan Chang, MD; Javier Villanueva-Meyer, MD; and Annette Molinaro, PhD

Combined 1H and hyperpolarized 13C metabolic imaging techniques can resolve ambiguities associated with current anatomic imaging methods and evaluate metabolic signatures that are specific for different glioma subgroups. Project 4 will conduct the first patient studies using two new hyperpolarized agents that are associated with changes in metabolism in IDH+ glioma. The most appropriate parameters for acquiring the metabolic data will be determined and applied to patients from the three most common glioma subgroups.