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: 

Non-invasive assessment of telomere maintenance mechanisms in brain tumors.

Nature communications

Viswanath P, Batsios G, Mukherjee J, Gillespie AM, Larson PEZ, Luchman HA, Phillips JJ, Costello JF, Pieper RO, Ronen SM

Unique challenges for glioblastoma immunotherapy - Discussions across neuro-oncology and non-neuro-oncology experts in cancer immunology.

Neuro-oncology

Chuntova P, Chow F, Watchmaker P, Galvez M, Heimberger AB, Newell EW, Diaz A, DePinho RA, Li MO, Wherry EJ, Mitchell D, Terabe M, Wainwright DA, Berzofsky JA, Herold-Mende C, Heath JR, Lim M, Margolin KA, Chiocca EA, Kasahara N, Ellingson BM, Brown C, Chen Y, Fecci P, Reardon DA, Dunn GP, Liau LM, Costello JF, Wick W, Cloughesy T, Timmer WC, Wen PY, Prins RM, Platten M, Okada H

Prostate Cancer Progression and the Epigenome.

The New England journal of medicine

Arap W, Pasqualini R, Costello JF

MGMT promoter methylation level in newly diagnosed low-grade glioma is a predictor of hypermutation at recurrence.

Neuro-oncology

Mathur R, Zhang Y, Grimmer MR, Hong C, Zhang M, Bollam S, Petrecca K, Clarke J, Berger MS, Phillips JJ, Oberheim-Bush NA, Molinaro AM, Chang SM, Costello JF

Functional analysis of low-grade glioma genetic variants predicts key target genes and transcription factors.

Neuro-oncology

Manjunath M, Yan J, Youn Y, Drucker KL, Kollmeyer TM, McKinney AM, Zazubovich V, Zhang Y, Costello JF, Eckel-Passow J, Selvin PR, Jenkins RB, Song JS