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: 

Deuterium metabolic imaging reports on TERT expression and early response to therapy in cancer.

Clinical cancer research : an official journal of the American Association for Cancer Research

Batsios G, Taglang C, Tran M, Stevers N, Barger C, Gillespie AM, Ronen SM, Costello JF, Viswanath P

Meningioma DNA methylation groups identify biological drivers and therapeutic vulnerabilities.

Nature genetics

Choudhury A, Magill ST, Eaton CD, Prager BC, Chen WC, Cady MA, Seo K, Lucas CG, Casey-Clyde TJ, Vasudevan HN, Liu SJ, Villanueva-Meyer JE, Lam TC, Pu JK, Li LF, Leung GK, Swaney DL, Zhang MY, Chan JW, Qiu Z, Martin MV, Susko MS, Braunstein SE, Bush NAO, Schulte JD, Butowski N, Sneed PK, Berger MS, Krogan NJ, Perry A, Phillips JJ, Solomon DA, Costello JF, McDermott MW, Rich JN, Raleigh DR

Imaging biomarkers of TERT or GABPB1 silencing in TERT-positive glioblastoma.

Neuro-oncology

Minami N, Hong D, Stevers N, Barger CJ, Radoul M, Hong C, Chen L, Kim Y, Batsios G, Gillespie AM, Pieper RO, Costello JF, Viswanath P, Ronen SM

TERT promoter C228T mutation in neural progenitors confers growth advantage following telomere shortening in vivo.

Neuro-oncology

Miki S, Koga T, Mckinney AM, Parisian AD, Tadokoro T, Vadla R, Masala M, Hevner RF, Costello JF, Furnari F

PI3K/AKT/mTOR signaling pathway activity in IDH-mutant diffuse glioma and clinical implications.

Neuro-oncology

Mohamed E, Kumar A, Zhang Y, Wang AS, Chen K, Lim Y, Shai A, Taylor JW, Clarke J, Hilz S, Berger MS, Solomon DA, Costello JF, Molinaro AM, Phillips JJ