Research Summary

I am an academic neuro-oncologist involved in clinical care, clinical research and teaching. I have formal training and extensive experience in clinical trial design, implementation and analysis, including investigator-initiated, sponsored and multi-institutional consortium and cooperative group studies testing new treatments and treatment combinations in gliomas.  I have been the Chair of the Cancer Center’s Protocol Review and Monitoring Committee (PRMC) since 2018.  My current research foci include (1) precision medicine approaches to glioma treatment, (2) immunotherapy, in particular development of novel CAR-T therapies in glioma in collaboration with Drs. Hideho Okada and Wendell Lim, and (3) evaluation of serial blood immune profiles as a marker of clinical outcome in glioblastoma patients, using methylation arrays.  I am a Co-Associate Director of the Clinical Core for the UCSF (P01) Program Project Grant  focused on integrating advances in physiologic and metabolic imaging with tissue biomarkers in order to optimize the management of patients with molecular subtypes of glioma.  In addition, I am co-PI of projects both in the UCSF Brain Tumor Center’s U19 grant in collaboration with Northwestern University and in the UCSF Brain Tumor Center’s SPORE grant.

Education

California Institute of Technology (Caltech), Pasadena, CA, B.S., 1995, Chemistry, With Honor
University of California, San Francisco, M.D., 2002, Medicine
University of California, Berkeley, M.P.H., 2001, Health Policy and Mgmt
St. Mary’s Medical Center, San Francisco, 06/03, Intern, Internal Medicine
University of California, San Francisco, 06/06, Resident, Neurology
Memorial Sloan-Kettering Cancer Center, 06/08, Fellow, Neuro-oncology

Honors & Awards

  • 1999
    Nomination for “An Outstanding Lecture” UCSF Class of 2001
  • 2000
    University Fellowship, UC-Berkeley
  • 2000
    Award for “An Outstanding Lecture” UCSF Class of 2002
  • 2001
    UCSF Class of 1966 Scholarship
  • 2003
    Intern of the Year, St. Mary’s Medical Center
  • 2008
    ASCO Foundation Merit Award
  • 2009
    Awarded a fellowship to the 2nd Annual Clinical Trials Methods Course in Neurology, in Vail, Colorado, August 17-23, 2009; the course is sponsored by NINDS

Selected Publications

  1. Saijo A, Ogino H, Butowski NA, Tedesco MR, Gibson D, Watchmaker PB, Okada K, Wang AS, Shai A, Salazar AM, Molinaro AM, Rabbitt JE, Shahin M, Perry A, Clarke JL, Taylor JW, Daras M, Oberheim Bush NA, Hervey-Jumper SL, Phillips JJ, Chang SM, Hilf N, Mayer-Mokler A, Keler T, Berger MS, Okada H. A combinatory vaccine with IMA950 plus varlilumab promotes effector memory T-cell differentiation in the peripheral blood of patients with low-grade gliomas. Neuro Oncol. 2023 Sep 27.  View on PubMed
  2. Autry AW, Vaziri S, LaFontaine M, Gordon JW, Chen HY, Kim Y, Villanueva-Meyer JE, Molinaro A, Clarke JL, Oberheim Bush NA, Xu D, Lupo JM, Larson PEZ, Vigneron DB, Chang SM, Li Y. Multi-parametric hyperpolarized 13C/1H imaging reveals Warburg-related metabolic dysfunction and associated regional heterogeneity in high-grade human gliomas. Neuroimage Clin. 2023 Aug 18; 39:103501.  View on PubMed
  3. Mellinghoff IK, Lu M, Wen PY, Taylor JW, Maher EA, Arrillaga-Romany I, Peters KB, Ellingson BM, Rosenblum MK, Chun S, Le K, Tassinari A, Choe S, Toubouti Y, Schoenfeld S, Pandya SS, Hassan I, Steelman L, Clarke JL, Cloughesy TF. Author Correction: Vorasidenib and ivosidenib in IDH1-mutant low-grade glioma: a randomized, perioperative phase 1 trial. Nat Med. 2023 Jul 03.  View on PubMed
  4. Mellinghoff IK, Lu M, Wen PY, Taylor JW, Maher EA, Arrillaga-Romany I, Peters KB, Ellingson BM, Rosenblum MK, Chun S, Le K, Tassinari A, Choe S, Toubouti Y, Schoenfeld S, Pandya SS, Hassan I, Steelman L, Clarke JL, Cloughesy TF. Vorasidenib and ivosidenib in IDH1-mutant low-grade glioma: a randomized, perioperative phase 1 trial. Nat Med. 2023 03; 29(3):615-622.  View on PubMed
  5. Tang E, Wiencke JK, Warrier G, Hansen H, McCoy L, Rice T, Bracci PM, Wrensch M, Taylor JW, Clarke JL, Koestler DC, Salas LA, Christensen BC, Kelsey KT, Molinaro AM. Evaluation of cross-platform compatibility of a DNA methylation-based glucocorticoid response biomarker. Clin Epigenetics. 2022 10 28; 14(1):136.  View on PubMed
  6. Zhang Y, Lucas CG, Young JS, Morshed RA, McCoy L, Oberheim Bush NA, Taylor JW, Daras M, Butowski NA, Villanueva-Meyer JE, Cha S, Wrensch M, Wiencke JK, Lee JC, Pekmezci M, Phillips JJ, Perry A, Bollen AW, Aghi MK, Theodosopoulos P, Chang EF, Hervey-Jumper SL, Berger MS, Clarke JL, Chang SM, Molinaro AM, Solomon DA. Prospective genomically guided identification of "early/evolving" and "undersampled" IDH-wildtype glioblastoma leads to improved clinical outcomes. Neuro Oncol. 2022 10 03; 24(10):1749-1762.  View on PubMed
  7. Vaziri S, Autry AW, Lafontaine M, Kim Y, Gordon JW, Chen HY, Hu JY, Lupo JM, Chang SM, Clarke JL, Villanueva-Meyer JE, Bush NAO, Xu D, Larson PEZ, Vigneron DB, Li Y. Assessment of higher-order singular value decomposition denoising methods on dynamic hyperpolarized [1-13C]pyruvate MRI data from patients with glioma. Neuroimage Clin. 2022; 36:103155.  View on PubMed
  8. Lucas CG, Sloan EA, Gupta R, Wu J, Pratt D, Vasudevan HN, Ravindranathan A, Barreto J, Williams EA, Shai A, Whipple NS, Bruggers CS, Maher O, Nabors B, Rodriguez M, Samuel D, Brown M, Carmichael J, Lu R, Mirchia K, Sullivan DV, Pekmezci M, Tihan T, Bollen AW, Perry A, Banerjee A, Mueller S, Gupta N, Hervey-Jumper SL, Oberheim Bush NA, Daras M, Taylor JW, Butowski NA, de Groot J, Clarke JL, Raleigh DR, Costello JF, Phillips JJ, Reddy AT, Chang SM, Berger MS, Solomon DA. Multiplatform molecular analyses refine classification of gliomas arising in patients with neurofibromatosis type 1. Acta Neuropathol. 2022 Oct; 144(4):747-765.  View on PubMed
  9. Bracci PM, Rice T, Hansen HM, Francis SS, Lee S, McCoy LS, Shrestha PP, Warrier G, Clarke JL, Molinaro AM, Taylor JW, Wiencke JK, Wrensch MR. Pre-surgery immune profiles of adult glioma patients. J Neurooncol. 2022 Aug; 159(1):103-115.  View on PubMed
  10. Nayak L, Standifer N, Dietrich J, Clarke JL, Dunn GP, Lim M, Cloughesy T, Gan HK, Flagg E, George E, Gaffey S, Hayden J, Holcroft C, Wen PY, Macri M, Park AJ, Ricciardi T, Ryan A, Schwarzenberger P, Venhaus R, Reyes ML, Durham NM, Creasy T, Huang RY, Kaley T, Reardon DA. Circulating Immune Cell and Outcome Analysis from the Phase II Study of PD-L1 Blockade with Durvalumab for Newly Diagnosed and Recurrent Glioblastoma. Clin Cancer Res. 2022 06 13; 28(12):2567-2578.  View on PubMed
  11. Calabrese E, Rudie JD, Rauschecker AM, Villanueva-Meyer JE, Clarke JL, Solomon DA, Cha S. Combining radiomics and deep convolutional neural network features from preoperative MRI for predicting clinically relevant genetic biomarkers in glioblastoma. Neurooncol Adv. 2022 Jan-Dec; 4(1):vdac060.  View on PubMed
  12. Molinaro AM, Wiencke JK, Warrier G, Koestler DC, Chunduru P, Lee JY, Hansen HM, Lee S, Anguiano J, Rice T, Bracci PM, McCoy L, Salas LA, Christensen BC, Wrensch M, Kelsey KT, Taylor JW, Clarke JL. Interactions of Age and Blood Immune Factors and Noninvasive Prediction of Glioma Survival. J Natl Cancer Inst. 2022 03 08; 114(3):446-457.  View on PubMed
  13. Ogino H, Taylor JW, Nejo T, Gibson D, Watchmaker PB, Okada K, Saijo A, Tedesco MR, Shai A, Wong CM, Rabbitt JE, Olin MR, Moertel CL, Nishioka Y, Salazar AM, Molinaro AM, Phillips JJ, Butowski NA, Clarke JL, Oberheim Bush NA, Hervey-Jumper SL, Theodosopoulos P, Chang SM, Berger MS, Okada H. Randomized trial of neoadjuvant vaccination with tumor-cell lysate induces T cell response in low-grade gliomas. J Clin Invest. 2022 02 01; 132(3).  View on PubMed
  14. Lucas CG, Gupta R, Wu J, Shah K, Ravindranathan A, Barreto J, Gener M, Ginn KF, Prall OWJ, Xu H, Kee D, Ko HS, Yaqoob N, Zia N, Florez A, Cha S, Perry A, Clarke JL, Chang SM, Berger MS, Solomon DA. EWSR1-BEND2 fusion defines an epigenetically distinct subtype of astroblastoma. Acta Neuropathol. 2022 01; 143(1):109-113.  View on PubMed
  15. Lucas CG, Mueller S, Reddy A, Taylor JW, Oberheim Bush NA, Clarke JL, Chang SM, Gupta N, Berger MS, Perry A, Phillips JJ, Solomon DA. Diffuse hemispheric glioma, H3 G34-mutant: Genomic landscape of a new tumor entity and prospects for targeted therapy. Neuro Oncol. 2021 11 02; 23(11):1974-1976.  View on PubMed
  16. 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
  17. Akinduro OO, Garcia DP, Higgins DMO, Vivas-Buitrago T, Jentoft M, Solomon DA, Daniels DJ, Pennington Z, Sherman WJ, Delgardo M, Bydon M, Kalani MA, Zanazzi G, Tsankova N, Bendok BR, McCormick PC, Sciubba DM, Lo SL, Clarke JL, Abode-Iyamah K, Quiñones-Hinojosa A. A multicenter analysis of the prognostic value of histone H3 K27M mutation in adult high-grade spinal glioma. J Neurosurg Spine. 2021 Aug 20; 35(6):834-843.  View on PubMed
  18. Gupta R, Lucas CG, Wu J, Barreto J, Shah K, Simon IB, Casavilca-Zambrano S, Brathwaite C, Zhou H, Caccamo D, Gilani A, Kleinschmidt-DeMasters BK, Lee JC, Perry A, Clarke JL, Chang SM, Berger MS, Solomon DA. Low-grade glioneuronal tumors with FGFR2 fusion resolve into a single epigenetic group corresponding to 'Polymorphous low-grade neuroepithelial tumor of the young'. Acta Neuropathol. 2021 09; 142(3):595-599.  View on PubMed
  19. Mellinghoff IK, Penas-Prado M, Peters KB, Burris HA, Maher EA, Janku F, Cote GM, de la Fuente MI, Clarke JL, Ellingson BM, Chun S, Young RJ, Liu H, Choe S, Lu M, Le K, Hassan I, Steelman L, Pandya SS, Cloughesy TF, Wen PY. Vorasidenib, a Dual Inhibitor of Mutant IDH1/2, in Recurrent or Progressive Glioma; Results of a First-in-Human Phase I Trial. Clin Cancer Res. 2021 08 15; 27(16):4491-4499.  View on PubMed
  20. Muster R, Ko N, Smith W, Su H, Dickey MA, Nelson J, McCulloch CE, Sneed PK, Clarke JL, Saloner DA, Eisenmenger L, Kim H, Cooke DL. Proof-of-concept single-arm trial of bevacizumab therapy for brain arteriovenous malformation. BMJ Neurol Open. 2021; 3(1):e000114.  View on PubMed

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