Joseph F. Costello, PhD

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Joseph F. Costello, PhD

Professor in Residence, Department of Neurological Surgery, UCSF
Karen Osney Brownstein Endowed Chair in Molecular Neuro-Oncology, UCSF

jcostello@cc.ucsf.edu

Phone: (415) 514-1183 (voice)
Box 0875, UCSF
San Francisco, CA 94143-0875

UCSF Profiles | Lab Website

Cancer Center Membership

Program Member » Neurologic Oncology» Cancer Genetics

Research Summary

I am a Professor of Neurosurgery at UCSF and hold the Karen Osney Brownstein Endowed Chair in Neuro-oncology. I am the Director of the NIH-supported Training Program in Translational Brain Tumor Research at UCSF, and I recently served as the Director of the UCSF-based NIH Roadmap Epigenome Mapping Center. I am an Associate Member of the British Columbia Genome Sciences Centre. My laboratory is composed of molecular and computational biologists working alongside clinician-scientists. Our goal is to understand the full evolutionary history of human brain 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.

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.

Education

Marquette University, Milwaukee, WI, B.S., 1984-1988, Biology
Loyola University, Chicago, IL, Ph.D., 1990-1994, Neuroscience
Ludwig Institute, La Jolla, CA, Postdoc, 1994-1999, Molecular Biology of Brain Tumors


Professional Experience

  • 2000
    Assistant Professor and PI, Dept. of Neurological Surgery, Univ. of California San Francisco
  • 2005
    Director, Epigenetics Division of the UCSF CCC Program in Cell Cycling and Signaling
  • 2005-2010
    Associate Professor, Dept. of Neurological Surgery, University of California, San Francisco
  • 2005-present
    Karen Osney Brownstein Endowed Chair in Molecular Neuro-Oncology
  • 2008
    Director, NIH Roadmap Epigenome Mapping Center
  • 2010-present
    Professor, Department of Neurological Surgery, UCSF

Honors & Awards


  • 2005
    Human Epigenome Project committee
  • 2006
    Nature, Editors Roundatable on the future of Epigenetics
  • 2006
    Scientific Advisory Council, Brain Tumor Society (NBTS)
  • 2007
    International Epigenome Project (AHEAD), committee member
  • 2010
    Editorial Board, Neuro-Oncology and Journal of Neuro-Oncology
  • 2010
    International Human Epigenome Consortium (IHEC), member
  • 2010
    Outstanding Research Achievement Award, by Nature Biotechnology
  • 2010
    AACR Special Conferences Committee, member
  • 2013
    Keynote Lecture, Inaugural Clinical Epigenomics Conference
  • 2012
    Keynote Lecture, European Association for Neuro-Oncology Annual Meeting
  • 2013
    Chair, Gordon Conference on Genetics and Epigenetics
  • 2013
    Distinguished Lecture, DKFZ, Heidelberg
  • 2014-17
    Chair, Research Oversight Committee, Genome Quebec Pediatric Brain Tumors
  • 2012-17
    BC Genome Sciences Center, Associate Member
  • 2014
    Keynote Lecture, Medulloblastoma in the Mountains

Selected Publications

  1. Mazor T, Pankov A, Song JS, Costello JF. Intratumoral Heterogeneity of the Epigenome. Cancer Cell. 2016 Apr 11; 29(4):440-51.
    View on PubMed
  2. Gu J, Stevens M, Xing X, Li D, Zhang B, Payton JE, Oltz EM, Jarvis JN, Jiang K, Cicero T, Costello JF, Wang T. Mapping of Variable DNA Methylation Across Multiple Cell Types Defines a Dynamic Regulatory Landscape of the Human Genome. G3 (Bethesda). 2016; 6(4):973-86.
    View on PubMed
  3. Bell RJ, Rube HT, Xavier-Magalhães A, Costa BM, Mancini A, Song JS, Costello JF. Understanding TERT Promoter Mutations: A Common Path to Immortality. Mol Cancer Res. 2016 Apr; 14(4):315-23.
    View on PubMed
  4. Stieglitz E, Taylor-Weiner AN, Chang TY, Gelston LC, Wang YD, Mazor T, Esquivel E, Yu A, Seepo S, Olsen SR, Rosenberg M, Archambeault SL, Abusin G, Beckman K, Brown PA, Briones M, Carcamo B, Cooper T, Dahl GV, Emanuel PD, Fluchel MN, Goyal RK, Hayashi RJ, Hitzler J, Hugge C, Liu YL, Messinger YH, Mahoney DH, Monteleone P, Nemecek ER, Roehrs PA, Schore RJ, Stine KC, Takemoto CM, Toretsky JA, Costello JF, Olshen AB, Stewart C, Li Y, Ma J, Gerbing RB, Alonzo TA, Getz G, Gruber TA, Golub TR, Stegmaier K, Loh ML. Corrigendum: The genomic landscape of juvenile myelomonocytic leukemia. Nat Genet. 2015 Dec 29; 48(1):101.
    View on PubMed
  5. Grimmer MR, Costello JF. Cancer: Oncogene brought into the loop. Nature. 2016 Jan 7; 529(7584):34-5.
    View on PubMed
  6. Stieglitz E, Taylor-Weiner AN, Chang TY, Gelston LC, Wang YD, Mazor T, Esquivel E, Yu A, Seepo S, Olsen SR, Rosenberg M, Archambeault SL, Abusin G, Beckman K, Brown PA, Briones M, Carcamo B, Cooper T, Dahl GV, Emanuel PD, Fluchel MN, Goyal RK, Hayashi RJ, Hitzler J, Hugge C, Liu YL, Messinger YH, Mahoney DH, Monteleone P, Nemecek ER, Roehrs PA, Schore RJ, Stine KC, Takemoto CM, Toretsky JA, Costello JF, Olshen AB, Stewart C, Li Y, Ma J, Gerbing RB, Alonzo TA, Getz G, Gruber TA, Golub TR, Stegmaier K, Loh ML. The genomic landscape of juvenile myelomonocytic leukemia. Nat Genet. 2015 Nov; 47(11):1326-33.
    View on PubMed
  7. Mazor T, Pankov A, Johnson BE, Hong C, Hamilton EG, Bell RJ, Smirnov IV, Reis GF, Phillips JJ, Barnes MJ, Idbaih A, Alentorn A, Kloezeman JJ, Lamfers ML, Bollen AW, Taylor BS, Molinaro AM, Olshen AB, Chang SM, Song JS, Costello JF. DNA Methylation and Somatic Mutations Converge on the Cell Cycle and Define Similar Evolutionary Histories in Brain Tumors. Cancer Cell. 2015 Sep 14; 28(3):307-17.
    View on PubMed
  8. Bell RJ, Rube HT, Kreig A, Mancini A, Fouse SD, Nagarajan RP, Choi S, Hong C, He D, Pekmezci M, Wiencke JK, Wrensch MR, Chang SM, Walsh KM, Myong S, Song JS, Costello JF. Cancer. The transcription factor GABP selectively binds and activates the mutant TERT promoter in cancer. Science. 2015 May 29; 348(6238):1036-9.
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  9. Zhou X, Li D, Zhang B, Lowdon RF, Rockweiler NB, Sears RL, Madden PA, Smirnov I, Costello JF, Wang T. Epigenomic annotation of genetic variants using the Roadmap Epigenome Browser. Nat Biotechnol. 2015 Apr; 33(4):345-6.
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  10. van Thuijl HF, Mazor T, Johnson BE, Fouse SD, Aihara K, Hong C, Malmström A, Hallbeck M, Heimans JJ, Kloezeman JJ, Stenmark-Askmalm M, Lamfers ML, Saito N, Aburatani H, Mukasa A, Berger MS, Söderkvist P, Taylor BS, Molinaro AM, Wesseling P, Reijneveld JC, Chang SM, Ylstra B, Costello JF. Evolution of DNA repair defects during malignant progression of low-grade gliomas after temozolomide treatment. Acta Neuropathol. 2015 Apr; 129(4):597-607.
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  11. Integrative analysis of 111 reference human epigenomes. Nature. 2015 Feb 19; 518(7539):317-30.
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  12. Elliott G, Hong C, Xing X, Zhou X, Li D, Coarfa C, Bell RJ, Maire CL, Ligon KL, Sigaroudinia M, Gascard P, Tlsty TD, Harris RA, Schalkwyk LC, Bilenky M, Mill J, Farnham PJ, Kellis M, Marra MA, Milosavljevic A, Hirst M, Stormo GD, Wang T, Costello JF. Intermediate DNA methylation is a conserved signature of genome regulation. Nat Commun. 2015; 6:6363.
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  13. Gascard P, Bilenky M, Sigaroudinia M, Zhao J, Li L, Carles A, Delaney A, Tam A, Kamoh B, Cho S, Griffith M, Chu A, Robertson G, Cheung D, Li I, Heravi-Moussavi A, Moksa M, Mingay M, Hussainkhel A, Davis B, Nagarajan RP, Hong C, Echipare L, O'Geen H, Hangauer MJ, Cheng JB, Neel D, Hu D, McManus MT, Moore R, Mungall A, Ma Y, Plettner P, Ziv E, Wang T, Farnham PJ, Jones SJ, Marra MA, Tlsty TD, Costello JF, Hirst M. Epigenetic and transcriptional determinants of the human breast. Nat Commun. 2015; 6:6351.
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  14. Chen J, Hackett CS, Zhang S, Song YK, Bell RJ, Molinaro AM, Quigley DA, Balmain A, Song JS, Costello JF, Gustafson WC, Van Dyke T, Kwok PY, Khan J, Weiss WA. The genetics of splicing in neuroblastoma. Cancer Discov. 2015 Apr; 5(4):380-95.
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  15. Lowdon RF, Zhang B, Bilenky M, Mauro T, Li D, Gascard P, Sigaroudinia M, Farnham PJ, Bastian BC, Tlsty TD, Marra MA, Hirst M, Costello JF, Wang T, Cheng JB. Regulatory network decoded from epigenomes of surface ectoderm-derived cell types. Nat Commun. 2014; 5:5442.
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  16. Zheng CL, Wang NJ, Chung J, Moslehi H, Sanborn JZ, Hur JS, Collisson EA, Vemula SS, Naujokas A, Chiotti KE, Cheng JB, Fassihi H, Blumberg AJ, Bailey CV, Fudem GM, Mihm FG, Cunningham BB, Neuhaus IM, Liao W, Oh DH, Cleaver JE, LeBoit PE, Costello JF, Lehmann AR, Gray JW, Spellman PT, Arron ST, Huh N, Purdom E, Cho RJ. Transcription restores DNA repair to heterochromatin, determining regional mutation rates in cancer genomes. Cell Rep. 2014 Nov 20; 9(4):1228-34.
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  17. Clarke JL, Molinaro AM, Phillips JJ, Butowski NA, Chang SM, Perry A, Costello JF, DeSilva AA, Rabbitt JE, Prados MD. A single-institution phase II trial of radiation, temozolomide, erlotinib, and bevacizumab for initial treatment of glioblastoma. Neuro Oncol. 2014 Jul; 16(7):984-90.
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  18. Zhou X, Li D, Lowdon RF, Costello JF, Wang T. methylC Track: visual integration of single-base resolution DNA methylation data on the WashU EpiGenome Browser. Bioinformatics. 2014 Aug 1; 30(15):2206-7.
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  19. Nagarajan RP, Zhang B, Bell RJ, Johnson BE, Olshen AB, Sundaram V, Li D, Graham AE, Diaz A, Fouse SD, Smirnov I, Song J, Paris PL, Wang T, Costello JF. Recurrent epimutations activate gene body promoters in primary glioblastoma. Genome Res. 2014 May; 24(5):761-74.
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  20. Sturm D, Bender S, Jones DT, Lichter P, Grill J, Becher O, Hawkins C, Majewski J, Jones C, Costello JF, Iavarone A, Aldape K, Brennan CW, Jabado N, Pfister SM. Paediatric and adult glioblastoma: multiform (epi)genomic culprits emerge. Nat Rev Cancer. 2014 Feb; 14(2):92-107.
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