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.

Research Funding

  • September 1, 2010 - August 31, 2025 - Training Program in Translational Brain Tumor Research , Principal Investigator . Sponsor: NIH, Sponsor Award ID: T32CA151022
  • July 1, 2020 - June 30, 2025 - 3-D spatial approach to discover genomic effectors of immunosuppression during malignant transformation , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA244838
  • December 1, 2005 - July 31, 2024 - Noninvasive Metabolic Signatures to Improve Management of Molecular Subtypes of Glioma , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P01CA118816
  • September 1, 2017 - May 31, 2022 - Global Analyses of the Placental Epigenome in Preeclampsia , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01HD092419

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

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. Mohamed E, Kumar A, Zhang Y, Wang AS, Chen K, Lim Y, Shai A, Taylor JW, Clarke J, Hilz S, Berger MS, Solomon DA, Costello JF, Molinaro AM, Phillips JJ. PI3K/AKT/mTOR signaling pathway activity in IDH-mutant diffuse glioma and clinical implications. Neuro Oncol. 2022 09 01; 24(9):1471-1481.  View on PubMed
  2. Batsios G, Taglang C, Tran M, Stevers N, Barger C, Gillespie AM, Ronen SM, Costello JF, Viswanath P. Deuterium Metabolic Imaging Reports on TERT Expression and Early Response to Therapy in Cancer. Clin Cancer Res. 2022 08 15; 28(16):3526-3536.  View on PubMed
  3. Choudhury A, Magill ST, Eaton CD, Prager BC, Chen WC, Cady MA, Seo K, Lucas CG, Casey-Clyde TJ, Vasudevan HN, Liu SJ, Villanueva-Meyer JE, Lam TC, Pu JK, Li LF, Leung GK, Swaney DL, Zhang MY, Chan JW, Qiu Z, Martin MV, Susko MS, Braunstein SE, Bush NAO, Schulte JD, Butowski N, Sneed PK, Berger MS, Krogan NJ, Perry A, Phillips JJ, Solomon DA, Costello JF, McDermott MW, Rich JN, Raleigh DR. Meningioma DNA methylation groups identify biological drivers and therapeutic vulnerabilities. Nat Genet. 2022 05; 54(5):649-659.  View on PubMed
  4. Minami N, Hong D, Stevers N, Barger CJ, Radoul M, Hong C, Chen L, Kim Y, Batsios G, Gillespie AM, Pieper RO, Costello JF, Viswanath P, Ronen SM. Imaging biomarkers of TERT or GABPB1 silencing in TERT-positive glioblastoma. Neuro Oncol. 2022 Apr 23.  View on PubMed
  5. Miki S, Koga T, Mckinney AM, Parisian AD, Tadokoro T, Vadla R, Masala M, Hevner RF, Costello JF, Furnari F. TERT promoter C228T mutation in neural progenitors confers growth advantage following telomere shortening in vivo. Neuro Oncol. 2022 Mar 23.  View on PubMed
  6. Verburg N, Barthel FP, Anderson KJ, Johnson KC, Koopman T, Yaqub MM, Hoekstra OS, Lammertsma AA, Barkhof F, Pouwels PJW, Reijneveld JC, Rozemuller AJM, Beliën JAM, Boellaard R, Taylor MD, Das S, Costello JF, Vandertop WP, Wesseling P, de Witt Hamer PC, Verhaak RGW. Spatial concordance of DNA methylation classification in diffuse glioma. Neuro Oncol. 2021 12 01; 23(12):2054-2065.  View on PubMed
  7. Yu Y, Villanueva-Meyer J, Grimmer MR, Hilz S, Solomon DA, Choi S, Wahl M, Mazor T, Hong C, Shai A, Phillips JJ, Wainer BH, McDermott M, Haas-Kogan D, Taylor JW, Butowski N, Clarke JL, Berger MS, Molinaro AM, Chang SM, Costello JF, Oberheim Bush NA. Temozolomide-induced hypermutation is associated with distant recurrence and reduced survival after high-grade transformation of low-grade IDH-mutant gliomas. Neuro Oncol. 2021 11 02; 23(11):1872-1884.  View on PubMed
  8. Mathur R, Costello JF. Publisher Correction: Epigenomic contributions to tumor cell heterogeneity and plasticity. Nat Genet. 2021 Nov; 53(11):1622.  View on PubMed
  9. Mathur R, Costello JF. Epigenomic contributions to tumor cell heterogeneity and plasticity. Nat Genet. 2021 10; 53(10):1403-1404.  View on PubMed
  10. Viswanath P, Batsios G, Ayyappan V, Taglang C, Gillespie AM, Larson PEZ, Luchman HA, Costello JF, Pieper RO, Ronen SM. Metabolic imaging detects elevated glucose flux through the pentose phosphate pathway associated with TERT expression in low-grade gliomas. Neuro Oncol. 2021 09 01; 23(9):1509-1522.  View on PubMed
  11. Costello JF, Fisher SJ. The Placenta - Fast, Loose, and in Control. N Engl J Med. 2021 Jul 01; 385(1):87-89.  View on PubMed
  12. Zhang B, Kim MY, Elliot G, Zhou Y, Zhao G, Li D, Lowdon RF, Gormley M, Kapidzic M, Robinson JF, McMaster MT, Hong C, Mazor T, Hamilton E, Sears RL, Pehrsson EC, Marra MA, Jones SJM, Bilenky M, Hirst M, Wang T, Costello JF, Fisher SJ. Human placental cytotrophoblast epigenome dynamics over gestation and alterations in placental disease. Dev Cell. 2021 05 03; 56(9):1238-1252.e5.  View on PubMed
  13. Manjunath M, Yan J, Youn Y, Drucker KL, Kollmeyer TM, McKinney AM, Zazubovich V, Zhang Y, Costello JF, Eckel-Passow J, Selvin PR, Jenkins RB, Song JS. Functional analysis of low-grade glioma genetic variants predicts key target genes and transcription factors. Neuro Oncol. 2021 04 12; 23(4):638-649.  View on PubMed
  14. Amen AM, Fellmann C, Soczek KM, Ren SM, Lew RJ, Knott GJ, Park JE, McKinney AM, Mancini A, Doudna JA, Costello JF. Cancer-specific loss of TERT activation sensitizes glioblastoma to DNA damage. Proc Natl Acad Sci U S A. 2021 03 30; 118(13).  View on PubMed
  15. He D, Wu D, Muller S, Wang L, Saha P, Ahanger SH, Liu SJ, Cui M, Hong SJ, Jain M, Olson HE, Akeson M, Costello JF, Diaz A, Lim DA. miRNA-independent function of long noncoding pri-miRNA loci. Proc Natl Acad Sci U S A. 2021 03 30; 118(13).  View on PubMed
  16. Chuntova P, Chow F, Watchmaker PB, Galvez M, Heimberger AB, Newell EW, Diaz A, DePinho RA, Li MO, Wherry EJ, Mitchell D, Terabe M, Wainwright DA, Berzofsky JA, Herold-Mende C, Heath JR, Lim M, Margolin KA, Chiocca EA, Kasahara N, Ellingson BM, Brown CE, Chen Y, Fecci PE, Reardon DA, Dunn GP, Liau LM, Costello JF, Wick W, Cloughesy T, Timmer WC, Wen PY, Prins RM, Platten M, Okada H. Unique challenges for glioblastoma immunotherapy-discussions across neuro-oncology and non-neuro-oncology experts in cancer immunology. Meeting Report from the 2019 SNO Immuno-Oncology Think Tank. Neuro Oncol. 2021 03 25; 23(3):356-375.  View on PubMed
  17. Radoul M, Hong D, Gillespie AM, Najac C, Viswanath P, Pieper RO, Costello JF, Luchman HA, Ronen SM. Early Noninvasive Metabolic Biomarkers of Mutant IDH Inhibition in Glioma. Metabolites. 2021 Feb 13; 11(2).  View on PubMed
  18. Viswanath P, Batsios G, Mukherjee J, Gillespie AM, Larson PEZ, Luchman HA, Phillips JJ, Costello JF, Pieper RO, Ronen SM. Non-invasive assessment of telomere maintenance mechanisms in brain tumors. Nat Commun. 2021 01 04; 12(1):92.  View on PubMed
  19. Arap W, Pasqualini R, Costello JF. Prostate Cancer Progression and the Epigenome. N Engl J Med. 2020 12 03; 383(23):2287-2290.  View on PubMed
  20. Mathur R, Zhang Y, Grimmer MR, Hong C, Zhang M, Bollam S, Petrecca K, Clarke J, Berger MS, Phillips JJ, Oberheim-Bush NA, Molinaro AM, Chang SM, Costello JF. MGMT promoter methylation level in newly diagnosed low-grade glioma is a predictor of hypermutation at recurrence. Neuro Oncol. 2020 11 26; 22(11):1580-1590.  View on PubMed

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