University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Joseph F. Costello, PhD

Joseph F. Costello, PhD

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

Cancer Center Program Memberships

Neurologic Oncology

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. Kircher M, Xiong C, Martin B, Schubach M, Inoue F, Bell RJA, Costello JF, Shendure J, Ahituv N. Saturation mutagenesis of twenty disease-associated regulatory elements at single base-pair resolution. Nat Commun. 2019 Aug 08; 10(1):3583.
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  2. Lee JC, Mazor T, Lao R, Wan E, Diallo AB, Hill NS, Thangaraj N, Wendelsdorf K, Samuel D, Kline CN, Banerjee A, Auguste K, Raffel C, Gupta N, Berger M, Raleigh DR, Shai A, Phillips JJ, Bollen AW, Tihan T, Perry A, Costello J, Solomon DA. Recurrent KBTBD4 small in-frame insertions and absence of DROSHA deletion or DICER1 mutation differentiate pineal parenchymal tumor of intermediate differentiation (PPTID) from pineoblastoma. Acta Neuropathol. 2019 May; 137(5):851-854.
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  3. McMorris T, Hale BJ, Barwood M, Costello J, Corbett J. Corrigendum to "Effect of acute hypoxia on cognition: A systematic review and meta-regression analysis" Neurosci. Biobehav. Rev. 74 (2017) 225-232. Neurosci Biobehav Rev. 2019 03; 98:333.
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  4. Robinson JF, Kapidzic M, Hamilton EG, Chen H, Puckett KW, Zhou Y, Ona K, Parry E, Wang Y, Park JS, Costello JF, Fisher SJ. Genomic Profiling of BDE-47 Effects on Human Placental Cytotrophoblasts. Toxicol Sci. 2019 01 01; 167(1):211-226.
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  5. Mancini A, Xavier-Magalhães A, Woods WS, Nguyen KT, Amen AM, Hayes JL, Fellmann C, Gapinske M, McKinney AM, Hong C, Jones LE, Walsh KM, Bell RJA, Doudna JA, Costa BM, Song JS, Perez-Pinera P, Costello JF. Disruption of the ß1L Isoform of GABP Reverses Glioblastoma Replicative Immortality in a TERT Promoter Mutation-Dependent Manner. Cancer Cell. 2018 09 10; 34(3):513-528.e8.
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  6. Choi S, Yu Y, Grimmer MR, Wahl M, Chang SM, Costello JF. Temozolomide-associated hypermutation in gliomas. Neuro Oncol. 2018 09 03; 20(10):1300-1309.
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  7. Wallace AD, Wendt GA, Barcellos LF, de Smith AJ, Walsh KM, Metayer C, Costello JF, Wiemels JL, Francis SS. To ERV Is Human: A Phenotype-Wide Scan Linking Polymorphic Human Endogenous Retrovirus-K Insertions to Complex Phenotypes. Front Genet. 2018; 9:298.
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  8. Hayes J, Yu Y, Jalbert LE, Mazor T, Jones LE, Wood MD, Walsh KM, Bengtsson H, Hong C, Oberndorfer S, Roetzer T, Smirnov IV, Clarke JL, Aghi MK, Chang SM, Nelson SJ, Woehrer A, Phillips JJ, Solomon DA, Costello JF. Genomic analysis of the origins and evolution of multicentric diffuse lower-grade gliomas. Neuro Oncol. 2018 04 09; 20(5):632-641.
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  9. Xavier-Magalhães A, Gonçalves CS, Fogli A, Lourenço T, Pojo M, Pereira B, Rocha M, Lopes MC, Crespo I, Rebelo O, Tão H, Lima J, Moreira R, Pinto AA, Jones C, Reis RM, Costello JF, Arnaud P, Sousa N, Costa BM. The long non-coding RNA HOTAIR is transcriptionally activated by HOXA9 and is an independent prognostic marker in patients with malignant glioma. Oncotarget. 2018 Mar 20; 9(21):15740-15756.
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  10. Stieglitz E, Mazor T, Olshen AB, Geng H, Gelston LC, Akutagawa J, Lipka DB, Plass C, Flotho C, Chehab FF, Braun BS, Costello JF, Loh ML. Genome-wide DNA methylation is predictive of outcome in juvenile myelomonocytic leukemia. Nat Commun. 2017 12 19; 8(1):2127.
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  11. Dutoit V, Migliorini D, Ranzanici G, Marinari E, Widmer V, Lobrinus JA, Momjian S, Costello J, Walker PR, Okada H, Weinschenk T, Herold-Mende C, Dietrich PY. Antigenic expression and spontaneous immune responses support the use of a selected peptide set from the IMA950 glioblastoma vaccine for immunotherapy of grade II and III glioma. Oncoimmunology. 2018; 7(2):e1391972.
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  12. Campbell BB, Light N, Fabrizio D, Zatzman M, Fuligni F, de Borja R, Davidson S, Edwards M, Elvin JA, Hodel KP, Zahurancik WJ, Suo Z, Lipman T, Wimmer K, Kratz CP, Bowers DC, Laetsch TW, Dunn GP, Johanns TM, Grimmer MR, Smirnov IV, Larouche V, Samuel D, Bronsema A, Osborn M, Stearns D, Raman P, Cole KA, Storm PB, Yalon M, Opocher E, Mason G, Thomas GA, Sabel M, George B, Ziegler DS, Lindhorst S, Issai VM, Constantini S, Toledano H, Elhasid R, Farah R, Dvir R, Dirks P, Huang A, Galati MA, Chung J, Ramaswamy V, Irwin MS, Aronson M, Durno C, Taylor MD, Rechavi G, Maris JM, Bouffet E, Hawkins C, Costello JF, Meyn MS, Pursell ZF, Malkin D, Tabori U, Shlien A. Comprehensive Analysis of Hypermutation in Human Cancer. Cell. 2017 Nov 16; 171(5):1042-1056.e10.
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  13. Mazor T, Chesnelong C, Pankov A, Jalbert LE, Hong C, Hayes J, Smirnov IV, Marshall R, Souza CF, Shen Y, Viswanath P, Noushmehr H, Ronen SM, Jones SJM, Marra MA, Cairncross JG, Perry A, Nelson SJ, Chang SM, Bollen AW, Molinaro AM, Bengtsson H, Olshen AB, Weiss S, Phillips JJ, Luchman HA, Costello JF. Clonal expansion and epigenetic reprogramming following deletion or amplification of mutant IDH1. Proc Natl Acad Sci U S A. 2017 10 03; 114(40):10743-10748.
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  14. Venkatesan S, Swanton C, Taylor BS, Costello JF. Treatment-Induced Mutagenesis and Selective Pressures Sculpt Cancer Evolution. Cold Spring Harb Perspect Med. 2017 Aug 01; 7(8).
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  15. Wahl M, Chang SM, Phillips JJ, Molinaro AM, Costello JF, Mazor T, Alexandrescu S, Lupo JM, Nelson SJ, Berger M, Prados M, Taylor JW, Butowski N, Clarke JL, Haas-Kogan D. Probing the phosphatidylinositol 3-kinase/mammalian target of rapamycin pathway in gliomas: A phase 2 study of everolimus for recurrent adult low-grade gliomas. Cancer. 2017 Dec 01; 123(23):4631-4639.
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  16. Kim M, Costello J. DNA methylation: an epigenetic mark of cellular memory. Exp Mol Med. 2017 04 28; 49(4):e322.
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  17. Kohanbash G, Carrera DA, Shrivastav S, Ahn BJ, Jahan N, Mazor T, Chheda ZS, Downey KM, Watchmaker PB, Beppler C, Warta R, Amankulor NA, Herold-Mende C, Costello JF, Okada H. Isocitrate dehydrogenase mutations suppress STAT1 and CD8+ T cell accumulation in gliomas. J Clin Invest. 2017 Apr 03; 127(4):1425-1437.
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  18. Wahl M, Phillips JJ, Molinaro AM, Lin Y, Perry A, Haas-Kogan DA, Costello JF, Dayal M, Butowski N, Clarke JL, Prados M, Nelson S, Berger MS, Chang SM. Chemotherapy for adult low-grade gliomas: clinical outcomes by molecular subtype in a phase II study of adjuvant temozolomide. Neuro Oncol. 2017 02 01; 19(2):242-251.
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  19. McMorris T, Hale BJ, Barwood M, Costello J, Corbett J. Effect of acute hypoxia on cognition: A systematic review and meta-regression analysis. Neurosci Biobehav Rev. 2017 Mar; 74(Pt A):225-232.
    View on PubMed
  20. Ohba S, Mukherjee J, Johannessen TC, Mancini A, Chow TT, Wood M, Jones L, Mazor T, Marshall RE, Viswanath P, Walsh KM, Perry A, Bell RJ, Phillips JJ, Costello JF, Ronen SM, Pieper RO. Mutant IDH1 Expression Drives TERT Promoter Reactivation as Part of the Cellular Transformation Process. Cancer Res. 2016 11 15; 76(22):6680-6689.
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