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: 

Zinc Finger MYND-Type Containing 8 (ZMYND8) is epigenetically regulated in mutant Isocitrate Dehydrogenase 1 (IDH1) glioma to promote radioresistance.

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

Carney SV, Banerjee K, Mujeeb A, Zhu B, Haase S, Varela ML, Kadiyala P, Tronrud CE, Zhu Z, Mukherji D, Gorla P, Sun Y, Tagett R, N??ez FJ, Luo M, Luo W, Ljungman M, Liu Y, Xia Z, Schwendeman A, Qin T, Sartor MA, Costello JF, Cahill DP, Lowenstein PR, Castro MG

Hyperpolarized d-[1- 13C]gluconolactone imaging visualizes response to TERT or GABPB1 targeting therapy for glioblastoma.

Scientific reports

Minami N, Hong D, Taglang C, Batsios G, Gillespie AM, Viswanath P, Stevers N, Barger CJ, Costello JF, Ronen SM

Single-cell RNA sequencing and spatial transcriptomics reveal cancer-associated fibroblasts in glioblastoma with protumoral effects.

The Journal of clinical investigation

Jain S, Rick JW, Joshi RS, Beniwal A, Spatz J, Gill S, Chang AC, Choudhary N, Nguyen AT, Sudhir S, Chalif EJ, Chen JS, Chandra A, Haddad AF, Wadhwa H, Shah SS, Choi S, Hayes JL, Wang L, Yagnik G, Costello JF, Diaz A, Heiland DH, Aghi MK

Isocitrate dehydrogenase (IDH) mutant gliomas: A Society for Neuro-Oncology (SNO) consensus review on diagnosis, management, and future directions.

Neuro-oncology

Miller JJ, Gonzalez Castro LN, McBrayer S, Weller M, Cloughesy T, Portnow J, Andronesi O, Barnholtz-Sloan JS, Baumert BG, Berger MS, Bi WL, Bindra R, Cahill DP, Chang SM, Costello JF, Horbinski C, Huang RY, Jenkins RB, Ligon KL, Mellinghoff IK, Nabors LB, Platten M, Reardon DA, Shi DD, Schiff D, Wick W, Yan H, von Deimling A, van den Bent M, Kaelin WG, Wen PY

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