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: 

Epigenomic programming in early fetal brain development.

Epigenomics

Li L, Maire CL, Bilenky M, Carles A, Heravi-Moussavi A, Hong C, Tam A, Kamoh B, Cho S, Cheung D, Li I, Wong T, Nagarajan RP, Mungall AJ, Moore R, Wang T, Kleinman CL, Jabado N, Jones SJ, Marra MA, Ligon KL, Costello JF, Hirst M

The DNA methylation landscape of advanced prostate cancer.

Nature genetics

Zhao SG, Chen WS, Li H, Foye A, Zhang M, Sjöström M, Aggarwal R, Playdle D, Liao A, Alumkal JJ, Das R, Chou J, Hua JT, Barnard TJ, Bailey AM, Chow ED, Perry MD, Dang HX, Yang R, Moussavi-Baygi R, Zhang L, Alshalalfa M, Laura Chang S, Houlahan KE, Shiah YJ, Beer TM, Thomas G, Chi KN, Gleave M, Zoubeidi A, Reiter RE, Rettig MB, Witte O, Yvonne Kim M, Fong L, Spratt DE, Morgan TM, Bose R, Huang FW, Li H, Chesner L, Shenoy T, Goodarzi H, Asangani IA, Sandhu S, Lang JM, Mahajan NP, Lara PN, Evans CP, Febbo P, Batzoglou S, Knudsen KE, He HH, Huang J, Zwart W, Costello JF, Luo J, Tomlins SA, Wyatt AW, Dehm SM, Ashworth A, Gilbert LA, Boutros PC, Farh K, Chinnaiyan AM, Maher CA, Small EJ, Quigley DA, Feng FY

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

Gliomas arising in the setting of Li-Fraumeni syndrome stratify into two molecular subgroups with divergent clinicopathologic features.

Acta neuropathologica

Sloan EA, Hilz S, Gupta R, Cadwell C, Ramani B, Hofmann J, Kline CN, Banerjee A, Reddy A, Oberheim Bush NA, Chang S, Braunstein S, Chang EF, Raffel C, Gupta N, Sun PP, Kim JYH, Moes G, Alva E, Li R, Bruggers CS, Alashari M, Wetmore C, Garg S, Dishop M, Van Ziffle J, Onodera C, Devine P, Grenert JP, Lee JC, Phillips JJ, Pekmezci M, Tihan T, Bollen AW, Berger MS, Costello JF, Perry A, Solomon DA

Multiplatform Molecular Profiling Reveals Epigenomic Intratumor Heterogeneity in Ependymoma.

Cell reports

Liu SJ, Magill ST, Vasudevan HN, Hilz S, Villanueva-Meyer JE, Lastella S, Daggubati V, Spatz J, Choudhury A, Orr BA, Demaree B, Seo K, Ferris SP, Abate AR, Oberheim Bush NA, Bollen AW, McDermott MW, Costello JF, Raleigh DR