Joseph Costello, PhD

Dr. Costello’s research focuses on the role of genetic and epigenetic alterations in the formation of sporadic cancers, including brain tumors. His goal is to understand the full evolutionary history of human brain tumors, from the first mutation and epimutation through clonal selection and tumor recurrence.

Dr. Costello’s research team includes molecular and cell biologists, bioinformaticians, and clinicians, using next-generation sequencing to discover patterns and interdependencies of genetic mutations, epigenetic alterations and gene expression. They also investigate the influence of selective pressures such as temozolomide on tumor evolution. They recently reported on the cellular and genetic roots of glioblastoma from a whole-tumor perspective (Mathur, Cell, 2024), and an immunogenomics studies using our whole tumor sampling approach (Kwok, Nature, 2025), in collaboration with Dr. Okada.

They also investigate tumor cell immortality which involves TERT activation through mutation in the TERT promoter. TERT promoter mutation is the third most common mutation in human cancer, and the most frequent mutation in several CNS cancers including GBM. In collaboration with the Song lab, we discovered that the multimeric factor, GABP, is recruited by the mutation to activate TERT and immortalize brain cells, allowing them to proliferate indefinitely and evolve into tumors (Bell, Science, 2015; Stevers, Molecular Cell, 2025). In collaboration with the Doudna lab, we identified additional features of the GABP recruitment in glioma (Mancini, Cancer Cell, 2018), including recruitment by rare, recurrent duplications in the TERT promoter (Barger, Nature Communications, 2022). Understanding how the TERT promoter mutation drives tumorigenesis and tumor cell immortality offers insight into potential therapies.

Costello Lab Website >