Professor of Neurosurgery
Karen Osney Brownstein Endowed Chair in Neuro-Oncology
University of California, San Francisco
Dr. Joe Costello is a Professor of Neurosurgery at UCSF and holds the Karen Osney Brownstein Endowed Chair in Neuro-oncology. Dr. Costello is the Director of the NIH supported Training Program in Translational Brain Tumor Research at UCSF. He has substantial experience in teaching, mentoring, and scientific leadership. Examples of his activities include serving as mentor/co-mentor for undergraduate and medical student trainees, trainees at the PhD and postdoc level funded through F31, F99/K00 and F32 from NIH, medical residents on the Holman Path,NIH R25 or NIH F32, and junior faculty who have received K08 or K23 awards.
The Costello laboratory is composed of cell, molecular and computational biologists working alongside clinician-scientists. Our goal is to understand the full evolutionary history of human brain tumors, from the first mutation/epimutation and tumor immortality, through clonal selection and tumor recurrence. Our basic science research on the mechanism of tumor immortality is also a major theme in the Costello laboratory. Tumor cell immortality involves TERT activation through mutation in the TERT promoter. TERT promoter mutation is the most common non-coding mutation in human cancer, and the most frequent mutation in several CNS cancers including GBM and oligodendroglioma. We recently discovered the multimeric factor, GABP, which is recruited by the mutation to activate TERT and immortalize brain cells, allowing them to proliferate indefinitely and evolve into tumors. In follow-up experiments, a key GABPB1 isoform was identified that may be critical for therapeutic targeting to reverse tumor immortality specifically in tumor cells.
Dr. Costello has been collaborating with Dr. Okada, a cancer immunologist since 2014. His office is immediately adjacent to Dr. Costello’s office. We recently reported that IDH mutations in glioma cells lead to decreased STAT1 levels, which down-regulate T-cell-attracting chemokines, such as CXCL10, thereby inhibiting CD8+ T-cell accumulation in gliomas (Kohanbash, JCI, 2017). This is a novel immunosuppression mechanism in IDH-mutant gliomas. Dr. Costello also works with Dr. Okada on identification of glioma-associated antigens that can be targeted by immunotherapy (R21NS093654; Okada and Costello as co-PIs). Dr. Costello and Dr. Okada were awarded a 3 year grant from the Brain Tumor Funders Collaborative to explore 3D evolution and intratumoral heterogeneity of IDH mutant tumors that have transformed to malignant high grade tumors, in order to identify and refine immunotherapeutic opportunities for these recurrent and often heavily mutated tumors.