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
Mentorship Development: 

5/2021 - Sharpening Your Research Mentoring Skills

Websites

Publications: 

Spatial 3D genome organization reveals intratumor heterogeneity in primary glioblastoma samples.

Science advances

Wang Q, Wang J, Mathur R, Youngblood MW, Jin Q, Hou Y, Stasiak LA, Luan Y, Zhao H, Hilz S, Hong C, Chang SM, Lupo JM, Phillips JJ, Costello JF, Yue F

Tumour-wide RNA splicing aberrations generate actionable public neoantigens.

Nature

Kwok DW, Stevers NO, Etxeberria I, Nejo T, Colton Cove M, Chen LH, Jung J, Okada K, Lakshmanachetty S, Gallus M, Barpanda A, Hong C, Chan GKL, Liu J, Wu SH, Ramos E, Yamamichi A, Watchmaker PB, Ogino H, Saijo A, Du A, Grishanina NR, Woo J, Diaz A, Hervey-Jumper SL, Chang SM, Phillips JJ, Wiita AP, Klebanoff CA, Costello JF, Okada H

Longitudinal profiling of IDH-mutant astrocytomas reveals acquired RAS-MAPK pathway mutations associated with inferior survival.

Neuro-oncology advances

Rodriguez Almaraz E, Guerra GA, Al-Adli NN, Young JS, Dada A, Quintana D, Taylor JW, Oberheim Bush NA, Clarke JL, Butowski NA, de Groot J, Pekmezci M, Perry A, Bollen AW, Scheffler AW, Glidden DV, Phillips JJ, Costello JF, Chang EF, Hervey-Jumper S, Berger MS, Francis SS, Chang SM, Solomon DA

Longitudinal multimodal profiling of IDH-wildtype glioblastoma reveals the molecular evolution and cellular phenotypes underlying prognostically different treatment responses.

Neuro-oncology

Lucas CG, Al-Adli NN, Young JS, Gupta R, Morshed RA, Wu J, Ravindranathan A, Shai A, Oberheim Bush NA, Taylor JW, de Groot J, Villanueva-Meyer JE, Pekmezci M, Perry A, Bollen AW, Theodosopoulos PV, Aghi MK, Chang EF, Hervey-Jumper SL, Raleigh DR, Molinaro AM, Costello JF, Diaz AA, Clarke JL, Butowski NA, Phillips JJ, Chang SM, Berger MS, Solomon DA

Molecular biomarkers for assessing the heat-adapted phenotype: a narrative scoping review.

The journal of physiological sciences : JPS

Corbett J, Young JS, Tipton MJ, Costello JT, Williams TB, Walker EF, Lee BJ, Stevens CE