Joseph Costello, PhD

Professor
Department of Neurological Surgery
Research Overview: 

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: 

Glioblastoma evolution and heterogeneity from a 3D whole-tumor perspective.

Cell

Mathur R, Wang Q, Schupp PG, Nikolic A, Hilz S, Hong C, Grishanina NR, Kwok D, Stevers NO, Jin Q, Youngblood MW, Stasiak LA, Hou Y, Wang J, Yamaguchi TN, Lafontaine M, Shai A, Smirnov IV, Solomon DA, Chang SM, Hervey-Jumper SL, Berger MS, Lupo JM, Okada H, Phillips JJ, Boutros PC, Gallo M, Oldham MC, Yue F, Costello JF

Whole tumor analysis reveals early origin of the TERT promoter mutation and intercellular heterogeneity in TERT expression.

Neuro-oncology

Appin CL, Hong C, Suwala AK, Hilz S, Mathur R, Solomon DA, Smirnov IV, Stevers NO, Shai A, Wang A, Berger MS, Chang SM, Phillips JJ, Costello JF

"De novo replication repair deficient glioblastoma, IDH-wildtype" is a distinct glioblastoma subtype in adults that may benefit from immune checkpoint blockade.

Acta neuropathologica

Hadad S, Gupta R, Oberheim Bush NA, Taylor JW, Villanueva-Meyer JE, Young JS, Wu J, Ravindranathan A, Zhang Y, Warrier G, McCoy L, Shai A, Pekmezci M, Perry A, Bollen AW, Phillips JJ, Braunstein SE, Raleigh DR, Theodosopoulos P, Aghi MK, Chang EF, Hervey-Jumper SL, Costello JF, de Groot J, Butowski NA, Clarke JL, Chang SM, Berger MS, Molinaro AM, Solomon DA

Novel SOX10 indel mutations drive schwannomas through impaired transactivation of myelination gene programs.

Neuro-oncology

Williams EA, Ravindranathan A, Gupta R, Stevers NO, Suwala AK, Hong C, Kim S, Yuan JB, Wu J, Barreto J, Lucas CG, Chan E, Pekmezci M, LeBoit PE, Mully T, Perry A, Bollen A, Van Ziffle J, Devine WP, Reddy AT, Gupta N, Basnet K, Macaulay R, Malafronte P, Lee H, Yong WH, Williams KJ, Juratli TA, Mata DA, Huang RSP, Hiemenz MC, Pavlick DC, Frampton GM, Janovitz T, Ross JS, Chang SM, Berger MS, Jacques L, Song JS, Costello JF, Solomon DA

Challenges in the discovery of tumor-specific alternative splicing-derived cell-surface antigens in glioma.

bioRxiv : the preprint server for biology

Nejo T, Wang L, Leung KK, Wang A, Lakshmanachetty S, Gallus M, Kwok DW, Hong C, Chen LH, Carrera DA, Zhang MY, Stevers NO, Maldonado GC, Yamamichi A, Watchmaker P, Naik A, Shai A, Phillips JJ, Chang SM, Wiita AP, Wells JA, Costello JF, Diaz AA, Okada H