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

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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. Corrigendum: The genomic landscape of juvenile myelomonocytic leukemia. Nat Genet. 2015 Dec 29; 48(1):101.
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  2. Cancer: Oncogene brought into the loop. Nature. 2016 Jan 7; 529(7584):34-5.
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  3. The genomic landscape of juvenile myelomonocytic leukemia. Nat Genet. 2015 Oct 12.
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  4. 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.
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  5. 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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  6. Epigenomic annotation of genetic variants using the Roadmap Epigenome Browser. Nat Biotechnol. 2015 Apr; 33(4):345-6.
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  7. 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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  8. Intermediate DNA methylation is a conserved signature of genome regulation. Nat Commun. 2015; 6:6363.
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  9. Epigenetic and transcriptional determinants of the human breast. Nat Commun. 2015; 6:6351.
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  10. The genetics of splicing in neuroblastoma. Cancer Discov. 2015 Apr; 5(4):380-95.
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  11. Regulatory network decoded from epigenomes of surface ectoderm-derived cell types. Nat Commun. 2014; 5:5442.
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  12. 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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  13. 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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  14. 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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  15. Recurrent epimutations activate gene body promoters in primary glioblastoma. Genome Res. 2014 May; 24(5):761-74.
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  16. Paediatric and adult glioblastoma: multiform (epi)genomic culprits emerge. Nat Rev Cancer. 2014 Feb; 14(2):92-107.
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  17. Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma. Science. 2014 Jan 10; 343(6167):189-93.
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  18. Where are we now? And where are we going? A report from the Accelerate Brain Cancer Cure (ABC2) low-grade glioma research workshop. Neuro Oncol. 2014 Jan; 16(2):173-8.
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  19. Response of primary glioblastoma cells to therapy is patient specific and independent of cancer stem cell phenotype. Neuro Oncol. 2014 Mar; 16(3):361-71.
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  20. Targeted DNA demethylation and activation of endogenous genes using programmable TALE-TET1 fusion proteins. Nat Biotechnol. 2013 Dec; 31(12):1137-42.
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