Joseph Costello, PhD

Professor
Department of Neurological Surgery
jcostello@cc.ucsf.edu

The Costello laboratory is composed of molecular and computational biologists working alongside clinician-scientists.  Our goal is to understand the full life history of human tumors, from the first mutation and epimutation through clonal selection and tumor recurrence.  We use next-generation sequencing to discover patterns and interdependencies of genetic mutations, epigenetic alternations and gene expression changes. Current projects incorporate MRI guided tumor biopsies and treatment data with longitudinal genomics to allow the reconstruction of tumor evolution in the context of the human tumor in vivo.  In collaboration with the Okada laboratory, we will be exploring the application of immune therapies to target tumor specific mutations and tumors that emerge as hypermutated following chemotherapy.  On the gene level, we recently discovered the mechanism by which mutation in the TERT gene promoter leads to telomerase activation, and are pursuing further mechanistic and therapeutic studies aimed at reversing tumor cell immortalization. TERT promoter mutation is one of the most common mutations in cancer in adults.

Primary Thematic Area: 
Cancer Biology & Cell Signaling
Secondary Thematic Area: 
Human Genetics
Research Summary: 
Mechanistic and Translational Cancer Research using Genomic and Epigenomic Approaches

Websites

Publications: 

Clonal expansion and epigenetic reprogramming following deletion or amplification of mutant IDH1.

Proceedings of the National Academy of Sciences of the United States of America

Mazor T, Chesnelong C, Pankov A, Jalbert LE, Hong C, Hayes J, Smirnov IV, Marshall R, Souza CF, Shen Y, Viswanath P, Noushmehr H, Ronen SM, Jones SJM, Marra MA, Cairncross JG, Perry A, Nelson SJ, Chang SM, Bollen AW, Molinaro AM, Bengtsson H, Olshen AB, Weiss S, Phillips JJ, Luchman HA, Costello JF

Treatment-Induced Mutagenesis and Selective Pressures Sculpt Cancer Evolution.

Cold Spring Harbor perspectives in medicine

Venkatesan S, Swanton C, Taylor BS, Costello JF

Isocitrate dehydrogenase mutations suppress STAT1 and CD8+ T cell accumulation in gliomas.

The Journal of clinical investigation

Kohanbash G, Carrera DA, Shrivastav S, Ahn BJ, Jahan N, Mazor T, Chheda ZS, Downey KM, Watchmaker PB, Beppler C, Warta R, Amankulor NA, Herold-Mende C, Costello JF, Okada H

Chemotherapy for adult low-grade gliomas: clinical outcomes by molecular subtype in a phase II study of adjuvant temozolomide.

Neuro-oncology

Wahl M, Phillips JJ, Molinaro AM, Lin Y, Perry A, Haas-Kogan DA, Costello JF, Dayal M, Butowski N, Clarke JL, Prados M, Nelson S, Berger MS, Chang SM

Effect of acute hypoxia on cognition: A systematic review and meta-regression analysis.

Neuroscience and biobehavioral reviews

McMorris T, Hale BJ, Barwood M, Costello J, Corbett J