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
  • March 1, 1985 - August 31, 2021 - Center Core Grant for Vision Research , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P30EY005722
  • April 8, 2013 - March 31, 2019 - Imaging Guided Genomics of Malignant Transformation , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA169316
  • July 1, 2015 - June 30, 2018 - Antigens for Molecularly Targeted Vaccines for Progressive Glioma , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R21NS093654
  • September 30, 2008 - June 30, 2014 - Integrated Epigenetic Maps of Human Embryonic and Adult Cells , Principal Investigator . Sponsor: NIH, Sponsor Award ID: U01ES017154
  • January 1, 1983 - March 31, 2009 - General Clinical Research Center , Co-Investigator . Sponsor: NIH, Sponsor Award ID: M01RR002172
  • April 1, 2002 - September 30, 2007 - CONVERGENT MECHANISMS CONTRIBUTING TO CANCER , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01CA094971

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

  • 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. Kwok DW, Stevers NO, Etxeberria I, Nejo T, Colton Cove M, Chen LH, Jung J, Okada K, Lakshmanachetty S, Gallus M, Barpanda A, Hong C, Chan GKL, Liu J, Wu SH, Ramos E, Yamamichi A, Watchmaker PB, Ogino H, Saijo A, Du A, Grishanina NR, Woo J, Diaz A, Hervey-Jumper SL, Chang SM, Phillips JJ, Wiita AP, Klebanoff CA, Costello JF, Okada H. Tumour-wide RNA splicing aberrations generate actionable public neoantigens. Nature. 2025 Feb 19.  View on PubMed
  2. 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; 73(1):26.  View on PubMed
  3. Lucas CG, Al-Adli NN, Young JS, Gupta R, Morshed RA, Wu J, Ravindranathan A, Shai A, Oberheim Bush NA, Taylor JW, de Groot J, Villanueva-Meyer JE, Pekmezci M, Perry A, Bollen AW, Theodosopoulos PV, Aghi MK, Chang EF, Hervey-Jumper SL, Raleigh DR, Molinaro AM, Costello JF, Diaz AA, Clarke JL, Butowski NA, Phillips JJ, Chang SM, Berger MS, Solomon DA. Longitudinal multimodal profiling of IDH-wildtype glioblastoma reveals the molecular evolution and cellular phenotypes underlying prognostically different treatment responses. Neuro Oncol. 2025 Jan 12; 27(1):89-105.  View on PubMed
  4. Kwok DW, Okada H, Costello JF. Activating the dark genome to illuminate cancer vaccine targets. Nat Genet. 2024 Sep; 56(9):1770-1771.  View on PubMed
  5. Mender MJ, Ward AL, Cubillos LH, Kelberman MM, Costello JT, Temmar H, Wallace DM, Lin ET, Lam JLW, Willsey MS, Ganesh Kumar N, Kung TA, Patil PG, Chestek CA. Functional Electrical Stimulation and Brain-Machine Interfaces for Simultaneous Control of Wrist and Finger Flexion. bioRxiv. 2024 Aug 12.  View on PubMed
  6. 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. Cancers (Basel). 2024 Jul 01; 16(13).  View on PubMed
  7. Stevers NO, Costello JF. Telomeres in glioma: Maintenance mechanisms to therapeutic potential. Neuro Oncol. 2024 06 03; 26(6):1025-1026.  View on PubMed
  8. Beccari S, Mohamed E, Voong V, Hilz S, Lafontaine M, Shai A, Lim Y, Martinez J, Switzman B, Yu RL, Lupo JM, Chang EF, Hervey-Jumper SL, Berger MS, Costello JF, Phillips JJ. Quantitative Assessment of Preanalytic Variables on Clinical Evaluation of PI3/AKT/mTOR Signaling Activity in Diffuse Glioma. Mod Pathol. 2024 Jun; 37(6):100488.  View on PubMed
  9. 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. 2024 04 05; 26(4):640-652.  View on PubMed
  10. 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. 2024 Mar 18.  View on PubMed
  11. 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 PB, 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. Sci Rep. 2024 03 16; 14(1):6362.  View on PubMed
  12. Temmar H, Willsey MS, Costello JT, Mender MJ, Cubillos LH, Lam JL, Wallace DM, Kelberman MM, Patil PG, Chestek CA. Artificial neural network for brain-machine interface consistently produces more naturalistic finger movements than linear methods. bioRxiv. 2024 Mar 05.  View on PubMed
  13. 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 01 18; 187(2):446-463.e16.  View on PubMed
  14. 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 12 11; 147(1):3.  View on PubMed
  15. 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 12 08; 25(12):2221-2236.  View on PubMed
  16. 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
  17. 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
  18. 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 10 17; 73(1):26.  View on PubMed
  19. 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
  20. 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

Go to UCSF Profiles, powered by CTSI