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: 

Multiplatform genomic profiling and magnetic resonance imaging identify mechanisms underlying intratumor heterogeneity in meningioma.

Nature communications

Magill ST, Vasudevan HN, Seo K, Villanueva-Meyer JE, Choudhury A, John Liu S, Pekmezci M, Findakly S, Hilz S, Lastella S, Demaree B, Braunstein SE, Bush NAO, Aghi MK, Theodosopoulos PV, Sneed PK, Abate AR, Berger MS, McDermott MW, Lim DA, Ullian EM, Costello JF, Raleigh DR

Glutamate is a non-invasive metabolic biomarker of IDH1 mutant glioma response to temozolomide treatment.

Cancer research

Subramani E, Radoul M, Najac C, Batsios G, Molloy AR, Hong D, Gillespie AM, Delos Santos R, Viswanath P, Costello JF, Pieper RO, Ronen SM

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

Patient-derived cells from recurrent tumors that model the evolution of IDH-mutant glioma.

Neuro-oncology advances

Jones LE, Hilz S, Grimmer MR, Mazor T, Najac C, Mukherjee J, McKinney A, Chow T, Pieper RO, Ronen SM, Chang SM, Phillips JJ, Costello JF

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