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

  • July 1, 2020 - June 30, 2025 - 3-D spatial approach to discover genomic effectors of immunosuppression during malignant transformation, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: R01CA244838
  • September 1, 2017 - May 31, 2022 - Global Analyses of the Placental Epigenome in Preeclampsia, Principal Investigator. Sponsor: NIH/NICHD, Sponsor Award ID: R01HD092419
  • March 1, 1985 - August 31, 2021 - Center Core Grant for Vision Research, Co-Investigator. Sponsor: NIH, Sponsor Award ID: P30EY005722
  • September 1, 2010 - August 31, 2020 - Training Program in Translational Brain Tumor Research, Principal Investigator. Sponsor: NIH/NCI, Sponsor Award ID: T32CA151022

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. 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 May 28.  View on PubMed
  2. 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 Apr 20.  View on PubMed
  3. 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 Apr 17.  View on PubMed
  4. 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
  5. 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 Apr 05.  View on PubMed
  6. 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 Mar 30; 118(13).  View on PubMed
  7. 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 Mar 30; 118(13).  View on PubMed
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. Magill ST, Vasudevan HN, Seo K, Villanueva-Meyer JE, Choudhury A, John Liu S, Pekmezci M, Findakly S, Hilz S, Lastella S, Demaree B, Braunstein SE, Bush NAO, Aghi MK, Theodosopoulos PV, Sneed PK, Abate AR, Berger MS, McDermott MW, Lim DA, Ullian EM, Costello JF, Raleigh DR. Multiplatform genomic profiling and magnetic resonance imaging identify mechanisms underlying intratumor heterogeneity in meningioma. Nat Commun. 2020 09 23; 11(1):4803.  View on PubMed
  14. Subramani E, Radoul M, Najac C, Batsios G, Molloy AR, Hong D, Gillespie AM, Santos RD, Viswanath P, Costello JF, Pieper RO, Ronen SM. Glutamate Is a Noninvasive Metabolic Biomarker of IDH1-Mutant Glioma Response to Temozolomide Treatment. Cancer Res. 2020 11 15; 80(22):5098-5108.  View on PubMed
  15. Li L, Maire CL, Bilenky M, Carles A, Heravi-Moussavi A, Hong C, Tam A, Kamoh B, Cho S, Cheung D, Li I, Wong T, Nagarajan RP, Mungall AJ, Moore R, Wang T, Kleinman CL, Jabado N, Jones SJ, Marra MA, Ligon KL, Costello JF, Hirst M. Epigenomic programming in early fetal brain development. Epigenomics. 2020 06; 12(12):1053-1070.  View on PubMed
  16. Jones LE, Hilz S, Grimmer MR, Mazor T, Najac C, Mukherjee J, McKinney A, Chow T, Pieper RO, Ronen SM, Chang SM, Phillips JJ, Costello JF. Patient-derived cells from recurrent tumors that model the evolution of IDH-mutant glioma. Neurooncol Adv. 2020 Jan-Dec; 2(1):vdaa088.  View on PubMed
  17. Zhao SG, Chen WS, Li H, Foye A, Zhang M, Sjöström M, Aggarwal R, Playdle D, Liao A, Alumkal JJ, Das R, Chou J, Hua JT, Barnard TJ, Bailey AM, Chow ED, Perry MD, Dang HX, Yang R, Moussavi-Baygi R, Zhang L, Alshalalfa M, Laura Chang S, Houlahan KE, Shiah YJ, Beer TM, Thomas G, Chi KN, Gleave M, Zoubeidi A, Reiter RE, Rettig MB, Witte O, Yvonne Kim M, Fong L, Spratt DE, Morgan TM, Bose R, Huang FW, Li H, Chesner L, Shenoy T, Goodarzi H, Asangani IA, Sandhu S, Lang JM, Mahajan NP, Lara PN, Evans CP, Febbo P, Batzoglou S, Knudsen KE, He HH, Huang J, Zwart W, Costello JF, Luo J, Tomlins SA, Wyatt AW, Dehm SM, Ashworth A, Gilbert LA, Boutros PC, Farh K, Chinnaiyan AM, Maher CA, Small EJ, Quigley DA, Feng FY. The DNA methylation landscape of advanced prostate cancer. Nat Genet. 2020 08; 52(8):778-789.  View on PubMed
  18. Sloan EA, Hilz S, Gupta R, Cadwell C, Ramani B, Hofmann J, Kline CN, Banerjee A, Reddy A, Oberheim Bush NA, Chang S, Braunstein S, Chang EF, Raffel C, Gupta N, Sun PP, Kim JYH, Moes G, Alva E, Li R, Bruggers CS, Alashari M, Wetmore C, Garg S, Dishop M, Van Ziffle J, Onodera C, Devine P, Grenert JP, Lee JC, Phillips JJ, Pekmezci M, Tihan T, Bollen AW, Berger MS, Costello JF, Perry A, Solomon DA. Gliomas arising in the setting of Li-Fraumeni syndrome stratify into two molecular subgroups with divergent clinicopathologic features. Acta Neuropathol. 2020 05; 139(5):953-957.  View on PubMed
  19. Liu SJ, Magill ST, Vasudevan HN, Hilz S, Villanueva-Meyer JE, Lastella S, Daggubati V, Spatz J, Choudhury A, Orr BA, Demaree B, Seo K, Ferris SP, Abate AR, Oberheim Bush NA, Bollen AW, McDermott MW, Costello JF, Raleigh DR. Multiplatform Molecular Profiling Reveals Epigenomic Intratumor Heterogeneity in Ependymoma. Cell Rep. 2020 02 04; 30(5):1300-1309.e5.  View on PubMed
  20. Penas-Prado M, Wu J, Cahill DP, Brat DJ, Costello JF, Kluetz PG, Cairncross JG, van den Bent M, Verhaak RGW, Aboud O, Burger P, Chang SM, Cordova C, Huang RY, Rowe LS, Taphoorn MJB, Gilbert MR, Armstrong TS, NCI-CONNECT Oligodendroglioma Workshop . Proceedings of the Comprehensive Oncology Network Evaluating Rare CNS Tumors (NCI-CONNECT) Oligodendroglioma Workshop. Neurooncol Adv. 2020 Jan-Dec; 2(1):vdz048.  View on PubMed

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