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


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

  • 2023
    Keynote Lecture, Gordon Conference on Cancer Genetics and Epigenetics
  • 2022
    Featured Speaker, 19th Annual Retreat, Brain Tumor Center, Wake Forest
  • 2022
    Keynote Lecture, Annual Cancer Center Retreat, University of North Carolina
  • 2020
    Hans-Dietrich Herrmann Lecture 2020
  • 2018
    Research Highlighted by General Electric, Five Coolest Things on Earth This Week - Week 72
  • 2016
    Keynote Plenary Lecture, Society for Neuro-Oncology Annual Meeting
  • 2016
    Keynote Lecture, Stanford University Cancer Center Annual Retreat
  • 2015
    AIRC Lecture, 11th World Conference on The Future of Science
  • 2014
    Oncology Society Lecture, Mayo Clinic
  • 2014
    Keynote Lecture, EMBO Workshop on Epigenetic Plasticity, Portugal
  • 2014
    Keynote Lecture, ISCO meeting, Cancer Genome: From Structure to Function
  • 2014
    Keynote Lecture, Medulloblastoma in the Mountains
  • 2013
    Distinguished Lecture, DKFZ, Heidelberg
  • 2013
    Keynote Lecture, Inaugural Clinical Epigenomics Conference
  • 2012
    Keynote Lecture, European Association for Neuro-Oncology Annual Meeting
  • 2010
    Outstanding Research Achievement Award, by Nature Biotechnology

Selected Publications

  1. Mathur R, Wang Q, Schupp PG, Nikolic A, Hilz S, Hong C, Grishanina NR, Kwok D, Stevers NO, Jin Q, Youngblood MW, Stasiak LA, Hou Y, Wang J, Yamaguchi TN, Lafontaine M, Shai A, Smirnov IV, Solomon DA, Chang SM, Hervey-Jumper SL, Berger MS, Lupo JM, Okada H, Phillips JJ, Boutros PC, Gallo M, Oldham MC, Yue F, Costello JF. Glioblastoma evolution and heterogeneity from a 3D whole-tumor perspective. Cell. 2024 Jan 18; 187(2):446-463.e16.  View on PubMed
  2. Appin CL, Hong C, Suwala AK, Hilz S, Mathur R, Solomon DA, Smirnov IV, Stevers NO, Shai A, Wang A, Berger MS, Chang SM, Phillips JJ, Costello JF. Whole tumor analysis reveals early origin of the TERT promoter mutation and intercellular heterogeneity in TERT expression. Neuro Oncol. 2023 Dec 23.  View on PubMed
  3. Hadad S, Gupta R, Oberheim Bush NA, Taylor JW, Villanueva-Meyer JE, Young JS, Wu J, Ravindranathan A, Zhang Y, Warrier G, McCoy L, Shai A, Pekmezci M, Perry A, Bollen AW, Phillips JJ, Braunstein SE, Raleigh DR, Theodosopoulos P, Aghi MK, Chang EF, Hervey-Jumper SL, Costello JF, de Groot J, Butowski NA, Clarke JL, Chang SM, Berger MS, Molinaro AM, Solomon DA. "De novo replication repair deficient glioblastoma, IDH-wildtype" is a distinct glioblastoma subtype in adults that may benefit from immune checkpoint blockade. Acta Neuropathol. 2023 Dec 11; 147(1):3.  View on PubMed
  4. Williams EA, Ravindranathan A, Gupta R, Stevers NO, Suwala AK, Hong C, Kim S, Yuan JB, Wu J, Barreto J, Lucas CG, Chan E, Pekmezci M, LeBoit PE, Mully T, Perry A, Bollen A, Van Ziffle J, Devine WP, Reddy AT, Gupta N, Basnet KM, Macaulay RJB, Malafronte P, Lee H, Yong WH, Williams KJ, Juratli TA, Mata DA, Huang RSP, Hiemenz MC, Pavlick DC, Frampton GM, Janovitz T, Ross JS, Chang SM, Berger MS, Jacques L, Song JS, Costello JF, Solomon DA. Novel SOX10 indel mutations drive schwannomas through impaired transactivation of myelination gene programs. Neuro Oncol. 2023 Dec 08; 25(12):2221-2236.  View on PubMed
  5. Nejo T, Wang L, Leung KK, Wang A, Lakshmanachetty S, Gallus M, Kwok DW, Hong C, Chen LH, Carrera DA, Zhang MY, Stevers NO, Maldonado GC, Yamamichi A, Watchmaker P, Naik A, Shai A, Phillips JJ, Chang SM, Wiita AP, Wells JA, Costello JF, Diaz AA, Okada H. Challenges in the discovery of tumor-specific alternative splicing-derived cell-surface antigens in glioma. bioRxiv. 2023 Nov 02.  View on PubMed
  6. Kwok DW, Stevers NO, Nejo T, Chen LH, Etxeberria I, Jung J, Okada K, Cove MC, Lakshmanachetty S, Gallus M, Barpanda A, Hong C, Chan GKL, Wu SH, Ramos E, Yamamichi A, Liu J, Watchmaker P, Ogino H, Saijo A, Du A, Grishanina N, Woo J, Diaz A, Chang SM, Phillips JJ, Wiita AP, Klebanoff CA, Costello JF, Okada H. Tumor-wide RNA splicing aberrations generate immunogenic public neoantigens. bioRxiv. 2023 Oct 20.  View on PubMed
  7. Schupp PG, Shelton SJ, Brody DJ, Eliscu R, Johnson BE, Mazor T, Kelley KW, Potts MB, McDermott MW, Huang EJ, Lim DA, Pieper RO, Berger MS, Costello JF, Phillips JJ, Oldham MC. Deconstructing Intratumoral Heterogeneity through Multiomic and Multiscale Analysis of Serial Sections. bioRxiv. 2023 Oct 18.  View on PubMed
  8. Corbett J, Young JS, Tipton MJ, Costello JT, Williams TB, Walker EF, Lee BJ, Stevens CE. Molecular biomarkers for assessing the heat-adapted phenotype: a narrative scoping review. J Physiol Sci. 2023 Oct 17; 73(1):26.  View on PubMed
  9. Costello JT, Temmar H, Cubillos LH, Mender MJ, Wallace DM, Willsey MS, Patil PG, Chestek CA. Balancing Memorization and Generalization in RNNs for High Performance Brain-Machine Interfaces. bioRxiv. 2023 May 28.  View on PubMed
  10. Carney SV, Banerjee K, Mujeeb A, Zhu B, Haase S, Varela ML, Kadiyala P, Tronrud CE, Zhu Z, Mukherji D, Gorla P, Sun Y, Tagett R, Núñez FJ, Luo M, Luo W, Ljungman M, Liu Y, Xia Z, Schwendeman A, Qin T, Sartor MA, Costello JF, Cahill DP, Lowenstein PR, Castro MG. Zinc Finger MYND-Type Containing 8 (ZMYND8) Is Epigenetically Regulated in Mutant Isocitrate Dehydrogenase 1 (IDH1) Glioma to Promote Radioresistance. Clin Cancer Res. 2023 05 01; 29(9):1763-1782.  View on PubMed
  11. Minami N, Hong D, Taglang C, Batsios G, Gillespie AM, Viswanath P, Stevers N, Barger CJ, Costello JF, Ronen SM. Hyperpolarized δ-[1- 13C]gluconolactone imaging visualizes response to TERT or GABPB1 targeting therapy for glioblastoma. Sci Rep. 2023 03 30; 13(1):5190.  View on PubMed
  12. Jain S, Rick JW, Joshi RS, Beniwal A, Spatz J, Gill S, Chang AC, Choudhary N, Nguyen AT, Sudhir S, Chalif EJ, Chen JS, Chandra A, Haddad AF, Wadhwa H, Shah SS, Choi S, Hayes JL, Wang L, Yagnik G, Costello JF, Diaz A, Heiland DH, Aghi MK. Single-cell RNA sequencing and spatial transcriptomics reveal cancer-associated fibroblasts in glioblastoma with protumoral effects. J Clin Invest. 2023 03 01; 133(5).  View on PubMed
  13. Miller JJ, Gonzalez Castro LN, McBrayer S, Weller M, Cloughesy T, Portnow J, Andronesi O, Barnholtz-Sloan JS, Baumert BG, Berger MS, Bi WL, Bindra R, Cahill DP, Chang SM, Costello JF, Horbinski C, Huang RY, Jenkins RB, Ligon KL, Mellinghoff IK, Nabors LB, Platten M, Reardon DA, Shi DD, Schiff D, Wick W, Yan H, von Deimling A, van den Bent M, Kaelin WG, Wen PY. Isocitrate dehydrogenase (IDH) mutant gliomas: A Society for Neuro-Oncology (SNO) consensus review on diagnosis, management, and future directions. Neuro Oncol. 2023 01 05; 25(1):4-25.  View on PubMed
  14. Miki S, Koga T, Mckinney AM, Parisian AD, Tadokoro T, Vadla R, Marsala 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 12 01; 24(12):2063-2075.  View on PubMed
  15. Willsey MS, Nason-Tomaszewski SR, Ensel SR, Temmar H, Mender MJ, Costello JT, Patil PG, Chestek CA. Real-time brain-machine interface in non-human primates achieves high-velocity prosthetic finger movements using a shallow feedforward neural network decoder. Nat Commun. 2022 Nov 12; 13(1):6899.  View on PubMed
  16. 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 11 02; 24(11):1898-1910.  View on PubMed
  17. McKinney AM, Mathur R, Stevers NO, Molinaro AM, Chang SM, Phillips JJ, Costello JF. GABP couples oncogene signaling to telomere regulation in TERT promoter mutant cancer. Cell Rep. 2022 09 20; 40(12):111344.  View on PubMed
  18. Barger CJ, Suwala AK, Soczek KM, Wang AS, Kim MY, Hong C, Doudna JA, Chang SM, Phillips JJ, Solomon DA, Costello JF. Conserved features of TERT promoter duplications reveal an activation mechanism that mimics hotspot mutations in cancer. Nat Commun. 2022 09 16; 13(1):5430.  View on PubMed
  19. 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
  20. 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

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