Research Summary

I am an academic neuro-oncologist involved in clinical care, clinical research and teaching. I have extensive experience as well as formal training in clinical trial development, implementation, and analysis, including investigator-initiated, sponsored, and multi-institutional consortium and cooperative group studies testing new treatments and treatment combinations in gliomas.

I am a Co-Associate Director of the Clinical Core for the new UCSF (P01) Program Project Grant to integrate advances in physiologic and metabolic imaging with tissue biomarkers in order to optimize the management of patients with glioblastoma (GBM). I am a co-investigator in all of the current neuro-oncology therapeutic trials, as well as in several non-therapeutic studies in the areas of diagnosis, epidemiology, and quality of life. In addition, I am the principal investigator at UCSF for six active protocols.

I am study chair for a single-institution investigator-initiated study treating newly-diagnosed, subtotally resected low-grade gliomas with chemotherapy, everolimus alone or in combination with temozolomide; the treatment is selected based on molecular parameters of the patient’s tumor. This study incorporates both imaging and molecular objectives, in collaboration with colleagues from the BTRC. I am also the PI of a phase I dose-escalation study in collaboration with Memorial Sloan-Kettering, combining bevacizumab (an anti-VEGF antibody) with hypofractionated stereotactic radiation in recurrent malignant glioma. In addition to anti-tumor properties, it is thought that bevacizumab has some radio-protective properties, which may allow the stereotactic radiation dose to be escalated higher than would otherwise be tolerated. Another study is a multi-center, randomized phase II study from the ALLIANCE. It randomizes patients between three arms: an autologous heat-shock protein vaccine followed by bevacizumab at recurrence, an autologous heat-shock protein vaccine in combination with bevacizumab, or bevacizumab alone. An additional multi-center study tests a checkpoint inhibitor, MEDI4736, in combination with radiation in patients with newly-diagnosed GBMs that are MGMT unmethylated, or in combination with bevacizumab in patients with recurrent, bevacizumab-refractory GBMs.

In addition to these clinical trials, we have an ongoing longitudinal study assessing quality of life in patients with malignant gliomas undergoing initial therapy, for which I am coordinating analysis.

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. 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; 1-10.  View on PubMed
  2. 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
  3. 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 Aug 15; 27(16):4491-4499.  View on PubMed
  4. 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
  5. 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
  6. Mende AL, Schulte JD, Okada H, Clarke JL. Current Advances in Immunotherapy for Glioblastoma. Curr Oncol Rep. 2021 01 26; 23(2):21.  View on PubMed
  7. Nayak L, Molinaro AM, Peters K, Clarke JL, Jordan JT, de Groot J, Nghiemphu L, Kaley T, Colman H, McCluskey C, Gaffey S, Smith TR, Cote DJ, Severgnini M, Yearley JH, Zhao Q, Blumenschein WM, Duda DG, Muzikansky A, Jain RK, Wen PY, Reardon DA. Randomized Phase II and Biomarker Study of Pembrolizumab plus Bevacizumab versus Pembrolizumab Alone for Patients with Recurrent Glioblastoma. Clin Cancer Res. 2021 02 15; 27(4):1048-1057.  View on PubMed
  8. Schulte JD, Buerki RA, Lapointe S, Molinaro AM, Zhang Y, Villanueva-Meyer JE, Perry A, Phillips JJ, Tihan T, Bollen AW, Pekmezci M, Butowski N, Oberheim Bush NA, Taylor JW, Chang SM, Theodosopoulos P, Aghi MK, Hervey-Jumper SL, Berger MS, Solomon DA, Clarke JL. Clinical, radiologic, and genetic characteristics of histone H3 K27M-mutant diffuse midline gliomas in adults. Neurooncol Adv. 2020 Jan-Dec; 2(1):vdaa142.  View on PubMed
  9. Lucas CG, Gupta R, Doo P, Lee JC, Cadwell CR, Ramani B, Hofmann JW, Sloan EA, Kleinschmidt-DeMasters BK, Lee HS, Wood MD, Grafe M, Born D, Vogel H, Salamat S, Puccetti D, Scharnhorst D, Samuel D, Cooney T, Cham E, Jin LW, Khatib Z, Maher O, Chamyan G, Brathwaite C, Bannykh S, Mueller S, Kline CN, Banerjee A, Reddy A, Taylor JW, Clarke JL, Oberheim Bush NA, Butowski N, Gupta N, Auguste KI, Sun PP, Roland JL, Raffel C, Aghi MK, Theodosopoulos P, Chang E, Hervey-Jumper S, Phillips JJ, Pekmezci M, Bollen AW, Tihan T, Chang S, Berger MS, Perry A, Solomon DA. Comprehensive analysis of diverse low-grade neuroepithelial tumors with FGFR1 alterations reveals a distinct molecular signature of rosette-forming glioneuronal tumor. Acta Neuropathol Commun. 2020 08 28; 8(1):151.  View on PubMed
  10. Autry AW, Gordon JW, Chen HY, LaFontaine M, Bok R, Van Criekinge M, Slater JB, Carvajal L, Villanueva-Meyer JE, Chang SM, Clarke JL, Lupo JM, Xu D, Larson PEZ, Vigneron DB, Li Y. Characterization of serial hyperpolarized 13C metabolic imaging in patients with glioma. Neuroimage Clin. 2020; 27:102323.  View on PubMed
  11. Alcaide-Leon P, Luks TL, Lafontaine M, Lupo JM, Okada H, Clarke JL, Villanueva-Meyer JE. Treatment-induced lesions in newly diagnosed glioblastoma patients undergoing chemoradiotherapy and heat-shock protein vaccine therapy. J Neurooncol. 2020 Jan; 146(1):71-78.  View on PubMed
  12. Sloan EA, Cooney T, Oberheim Bush NA, Buerki R, Taylor J, Clarke JL, Torkildson J, Kline C, Reddy A, Mueller S, Banerjee A, Butowski N, Chang S, Mummaneni PV, Chou D, Tan L, Theodosopoulos P, McDermott M, Berger M, Raffel C, Gupta N, Sun PP, Li Y, Shah V, Cha S, Braunstein S, Raleigh DR, Samuel D, Scharnhorst D, Fata C, Guo H, Moes G, Kim JYH, Koschmann C, Van Ziffle J, Onodera C, Devine P, Grenert JP, Lee JC, Pekmezci M, Phillips JJ, Tihan T, Bollen AW, Perry A, Solomon DA. Recurrent non-canonical histone H3 mutations in spinal cord diffuse gliomas. Acta Neuropathol. 2019 11; 138(5):877-881.  View on PubMed
  13. Chapman CH, Hara JH, Molinaro AM, Clarke JL, Oberheim Bush NA, Taylor JW, Butowski NA, Chang SM, Fogh SE, Sneed PK, Nakamura JL, Raleigh DR, Braunstein SE. Reirradiation of recurrent high-grade glioma and development of prognostic scores for progression and survival. Neurooncol Pract. 2019 Sep; 6(5):364-374.  View on PubMed
  14. Cloughesy TF, Mochizuki AY, Orpilla JR, Hugo W, Lee AH, Davidson TB, Wang AC, Ellingson BM, Rytlewski JA, Sanders CM, Kawaguchi ES, Du L, Li G, Yong WH, Gaffey SC, Cohen AL, Mellinghoff IK, Lee EQ, Reardon DA, O'Brien BJ, Butowski NA, Nghiemphu PL, Clarke JL, Arrillaga-Romany IC, Colman H, Kaley TJ, de Groot JF, Liau LM, Wen PY, Prins RM. Neoadjuvant anti-PD-1 immunotherapy promotes a survival benefit with intratumoral and systemic immune responses in recurrent glioblastoma. Nat Med. 2019 03; 25(3):477-486.  View on PubMed
  15. Morrison MA, Hess CP, Clarke JL, Butowski N, Chang SM, Molinaro AM, Lupo JM. Risk factors of radiotherapy-induced cerebral microbleeds and serial analysis of their size compared with white matter changes: A 7T MRI study in 113 adult patients with brain tumors. J Magn Reson Imaging. 2019 09; 50(3):868-877.  View on PubMed
  16. Stiner RK, Clarke JL, Sinha N, Chan J, Letourneau JM, Niemasik EE, Rabbitt JE, Chang SM, Butowski NA, Prados MD, Rosen MP. Attitudes toward fertility and fertility preservation in women with glioma. Neurooncol Pract. 2019 May; 6(3):218-225.  View on PubMed
  17. Taylor JW, Parikh M, Phillips JJ, James CD, Molinaro AM, Butowski NA, Clarke JL, Oberheim-Bush NA, Chang SM, Berger MS, Prados M. Phase-2 trial of palbociclib in adult patients with recurrent RB1-positive glioblastoma. J Neurooncol. 2018 Nov; 140(2):477-483.  View on PubMed
  18. Pekmezci M, Villanueva-Meyer JE, Goode B, Van Ziffle J, Onodera C, Grenert JP, Bastian BC, Chamyan G, Maher OM, Khatib Z, Kleinschmidt-DeMasters BK, Samuel D, Mueller S, Banerjee A, Clarke JL, Cooney T, Torkildson J, Gupta N, Theodosopoulos P, Chang EF, Berger M, Bollen AW, Perry A, Tihan T, Solomon DA. The genetic landscape of ganglioglioma. Acta Neuropathol Commun. 2018 06 07; 6(1):47.  View on PubMed
  19. Hayes J, Yu Y, Jalbert LE, Mazor T, Jones LE, Wood MD, Walsh KM, Bengtsson H, Hong C, Oberndorfer S, Roetzer T, Smirnov IV, Clarke JL, Aghi MK, Chang SM, Nelson SJ, Woehrer A, Phillips JJ, Solomon DA, Costello JF. Genomic analysis of the origins and evolution of multicentric diffuse lower-grade gliomas. Neuro Oncol. 2018 04 09; 20(5):632-641.  View on PubMed
  20. Leeper HE, Acquaye AA, Bell S, Clarke JL, Forst D, Laack NN, Link MJ, Taylor JW, Armstrong TS. Survivorship care planning in neuro-oncology. Neurooncol Pract. 2018 Mar; 5(1):3-9.  View on PubMed

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